1
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 1 of 38
In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100β In Detecting Traumatic Intracranial Lesions On CT
Linda Papa, MDCM, MSc1,2; Manoj K. Mittal, MD3,4; Jose Ramirez, MD2; Michelle Ramia, MD1; Sara Kirby, MD3; Salvatore Silvestri, MD1,2; Philip Giordano, MD1,2; Kurt Weber, MD1,2; Carolina F. Braga, BA1; Ciara N. Tan, BS, MSHS1; Neema J. Ameli, BS1; Marco Lopez, AS1; Mark Zonfrillo, MD, MSCE3,4
1
Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL
2
Department of Pediatric Emergency Medicine, Arnold Palmer Hospital for Children, Orlando, FL 3
Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia, PA
4
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
February 11, 2015
Word Count: 2,456 (excluding abstract and references) Tables & Figures: 6 Number of Authors: 13 Number of Institutions: 4
Linda Papa, MDCM, MSc Director of Academic Clinical Research and Attending Emergency Physician Department of Emergency Medicine
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
2
Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Manoj K. Mittal, MD Co-Chair, QI and Patient Safety Committee & Director, Emergency Department Extended Care Unit (EDECU) Division of Emergency Medicine Children's Hospital of Philadelphia Associate Professor of Clinical Pediatrics Perelman School of Medicine, University of Pennsylvania 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel: (215) 590 1944 Fax: (215) 590 4454 [email protected]
Jose Ramirez, MD Program Director, Pediatric Emergency Medicine Fellowship Attending Pediatric Emergency Physician
Page 2 of 38
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Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 3 of 38
Arnold Palmer Hospital for Children 92 W. Miller St. Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Michelle Ramia, MD Emergency Medicine Fellow Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Sara Kirby, MD Pediatric Emergency Medicine Fellow Arnold Palmer Hospital for Children 92 W. Miller St. Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
4
[email protected]
Salvatore Silvestri, MD Program Director, Emergency Medicine Residency Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Philip Giordano, MD Corporate Director, Research Operations, Orlando Health Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Page 4 of 38
5
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 38
Kurt Weber, MD Assistant Director, Research Operations, Orlando Health Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Carolina F. Braga, BA Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Ciara N. Tan, BS, MSHS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200)
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
6
Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Neema J. Ameli, BS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Marco Lopez, AS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Page 6 of 38
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Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 7 of 38
Mark Zonfrillo, MD, MSCE Attending Pediatric Emergency Physician Children's Hospital of Philadelphia Division of Emergency Medicine 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel.: 267-426-0294 Fax: 215-590-5425 [email protected]
CORRESPONDING AUTHOR:
Linda Papa, MDCM, MSc Director of Academic Clinical Research and Attending Emergency Physician Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
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ABSTRACT
In adults, Glial Fibrillary Acidic Protein (GFAP) has been shown to out-perform S100β in detecting intracranial lesions on CT in mild traumatic brain injury (TBI). This study examined the ability of GFAP and S100β to detect intracranial lesions on CT in children and youth involved in trauma. This prospective cohort study enrolled a convenience sample of children and youth at two pediatric and one adult Level 1 trauma centers following trauma, including both those with and without head trauma. Serum samples were obtained within 6 hours of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 155 pediatric trauma patients enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the 92 patients who had a head CT, 8 (9%) had intracranial lesions. The area under the ROC curve (AUC) for distinguishing head trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100β was 0.64 (0.55-0.74)(p0.15 ng/ml GFAP negative ≤0.15 ng/ml
CT positive
CT negative
Sensitivity
100% (60100)
8
54
Specificity
36% (2647)
0
30
NPV
100% (86100)
PPV
13% (6-24)
Table 2b. Classification Performance of Serum S100β
S100β positive ≥0.02 ng/ml S100β negative
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 1 of 38
In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100β In Detecting Traumatic Intracranial Lesions On CT
Linda Papa, MDCM, MSc1,2; Manoj K. Mittal, MD3,4; Jose Ramirez, MD2; Michelle Ramia, MD1; Sara Kirby, MD3; Salvatore Silvestri, MD1,2; Philip Giordano, MD1,2; Kurt Weber, MD1,2; Carolina F. Braga, BA1; Ciara N. Tan, BS, MSHS1; Neema J. Ameli, BS1; Marco Lopez, AS1; Mark Zonfrillo, MD, MSCE3,4
1
Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL
2
Department of Pediatric Emergency Medicine, Arnold Palmer Hospital for Children, Orlando, FL 3
Division of Emergency Medicine, Children's Hospital of Philadelphia, Philadelphia, PA
4
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
February 11, 2015
Word Count: 2,456 (excluding abstract and references) Tables & Figures: 6 Number of Authors: 13 Number of Institutions: 4
Linda Papa, MDCM, MSc Director of Academic Clinical Research and Attending Emergency Physician Department of Emergency Medicine
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
2
Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Manoj K. Mittal, MD Co-Chair, QI and Patient Safety Committee & Director, Emergency Department Extended Care Unit (EDECU) Division of Emergency Medicine Children's Hospital of Philadelphia Associate Professor of Clinical Pediatrics Perelman School of Medicine, University of Pennsylvania 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel: (215) 590 1944 Fax: (215) 590 4454 [email protected]
Jose Ramirez, MD Program Director, Pediatric Emergency Medicine Fellowship Attending Pediatric Emergency Physician
Page 2 of 38
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Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 3 of 38
Arnold Palmer Hospital for Children 92 W. Miller St. Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Michelle Ramia, MD Emergency Medicine Fellow Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Sara Kirby, MD Pediatric Emergency Medicine Fellow Arnold Palmer Hospital for Children 92 W. Miller St. Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
4
[email protected]
Salvatore Silvestri, MD Program Director, Emergency Medicine Residency Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Philip Giordano, MD Corporate Director, Research Operations, Orlando Health Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Page 4 of 38
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Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 5 of 38
Kurt Weber, MD Assistant Director, Research Operations, Orlando Health Attending Emergency Physician Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Carolina F. Braga, BA Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Ciara N. Tan, BS, MSHS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200)
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
6
Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Neema J. Ameli, BS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Marco Lopez, AS Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Page 6 of 38
7
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
Page 7 of 38
Mark Zonfrillo, MD, MSCE Attending Pediatric Emergency Physician Children's Hospital of Philadelphia Division of Emergency Medicine 3400 Civic Center Boulevard Philadelphia, PA 19104 Tel.: 267-426-0294 Fax: 215-590-5425 [email protected]
CORRESPONDING AUTHOR:
Linda Papa, MDCM, MSc Director of Academic Clinical Research and Attending Emergency Physician Department of Emergency Medicine Orlando Regional Medical Center 86 W. Underwood (S-200) Orlando, Florida, 32806 Tel.: 407-237-6329 Fax: 407-649-3083 [email protected]
Journal of Neurotrauma In Children and Youth With Mild and Moderate Traumatic Brain Injury GFAP Out-performs S100 In Detecting Traumatic Intracranial Lesions On CT (doi: 10.1089/neu.2015.3869) This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof.
8
ABSTRACT
In adults, Glial Fibrillary Acidic Protein (GFAP) has been shown to out-perform S100β in detecting intracranial lesions on CT in mild traumatic brain injury (TBI). This study examined the ability of GFAP and S100β to detect intracranial lesions on CT in children and youth involved in trauma. This prospective cohort study enrolled a convenience sample of children and youth at two pediatric and one adult Level 1 trauma centers following trauma, including both those with and without head trauma. Serum samples were obtained within 6 hours of injury. The primary outcome was the presence of traumatic intracranial lesions on CT scan. There were 155 pediatric trauma patients enrolled, 114 (74%) had head trauma and 41 (26%) had no head trauma. Out of the 92 patients who had a head CT, 8 (9%) had intracranial lesions. The area under the ROC curve (AUC) for distinguishing head trauma from no head trauma for GFAP was 0.84 (0.77-0.91) and for S100β was 0.64 (0.55-0.74)(p0.15 ng/ml GFAP negative ≤0.15 ng/ml
CT positive
CT negative
Sensitivity
100% (60100)
8
54
Specificity
36% (2647)
0
30
NPV
100% (86100)
PPV
13% (6-24)
Table 2b. Classification Performance of Serum S100β
S100β positive ≥0.02 ng/ml S100β negative
