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Article ; Online: Potential Blood-based Biomarkers for Concussion.

Papa, Linda

2016 Volume 24, Issue 3, Page(s) 108–115

Abstract: Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related ... ...

Abstract	Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
MeSH term(s)	Biomarkers/blood ; Brain Concussion/blood ; Brain Concussion/diagnosis ; Brain Concussion/diagnostic imaging ; Glial Fibrillary Acidic Protein/blood ; Humans ; Magnetic Resonance Imaging ; Neurofilament Proteins/blood ; Phosphopyruvate Hydratase/blood ; S100 Calcium Binding Protein beta Subunit/blood ; Tomography, X-Ray Computed ; Ubiquitin Thiolesterase/blood ; tau Proteins/blood
Chemical Substances	Biomarkers ; Glial Fibrillary Acidic Protein ; Neurofilament Proteins ; S100 Calcium Binding Protein beta Subunit ; S100B protein, human ; UCHL1 protein, human ; tau Proteins ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Phosphopyruvate Hydratase (EC 4.2.1.11)
Language	English
Publishing date	2016-07-30
Publishing country	United States
Document type	Journal Article ; Review ; Systematic Review
ZDB-ID	1174179-x
ISSN	1538-1951 ; 1062-8592
ISSN (online)	1538-1951
ISSN	1062-8592
DOI	10.1097/JSA.0000000000000117
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Article ; Online: Ketamine for acute suicidality in the emergency department: A systematic review.

Maguire, Lindsay / Bullard, Timothy / Papa, Linda

The American journal of emergency medicine

2021 Volume 43, Page(s) 54–58

Abstract: Introduction: There are no emergent pharmaceutical interventions for acute suicidal ideation, a common presenting complaint in the ED. Ketamine is a NMDA agonist frequently used by ED physicians for sedation and analgesia. Prior evidence from studies ... ...

Abstract	Introduction: There are no emergent pharmaceutical interventions for acute suicidal ideation, a common presenting complaint in the ED. Ketamine is a NMDA agonist frequently used by ED physicians for sedation and analgesia. Prior evidence from studies conducted in inpatient psychiatry units suggests that ketamine may have a role in alleviating treatment-resistant depression as well as suicidal ideation. Methods: PubMed, MEDLINE, and Cochrane reviews were queried for articles related to keywords ketamine, suicidality, suicidal ideation, and emergency department/room. Relevant articles were selected and reviewed by two separate authors. Results: Three relevant, prospective studies were identified with a mean sample size of 25.7. Each was performed using 0.2 mg/kg ketamine for individuals receiving active treatment. Each study reported a decrease in depressive symptoms among those receiving ketamine. One study reported a significant reduction in SI when compared to placebo at 90 min that became non-significant by 230 min. No significant adverse events were reported in any study. Conclusion: Current evidence suggests that ketamine is a promising, safe potential intervention for acute suicidality in the ED. Convincing evidence for efficacy of ketamine for acute suicidal ideation remains lacking, and this promising potential intervention should be further investigated.
MeSH term(s)	Adolescent ; Adult ; Aged ; Depressive Disorder/complications ; Emergency Service, Hospital/statistics & numerical data ; Excitatory Amino Acid Antagonists/administration & dosage ; Female ; Humans ; Ketamine/administration & dosage ; Male ; Middle Aged ; Suicidal Ideation ; Treatment Outcome ; Young Adult
Chemical Substances	Excitatory Amino Acid Antagonists ; Ketamine (690G0D6V8H)
Language	English
Publishing date	2021-01-14
Publishing country	United States
Document type	Journal Article ; Systematic Review
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2020.12.088
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Article: Age and sex differences in blood product transfusions and mortality in trauma patients at a level I trauma center.

Papa, Linda / Maguire, Lindsay / Thundiyil, Josef G / Ladde, Jay G / Miller, Susan A

Heliyon

2023 Volume 9, Issue 8, Page(s) e18890

Abstract: Objectives: Hemorrhage is a common complication of trauma. We evaluated age and sex differences in treatment with blood product transfusions and massive transfusions as well as in-hospital mortality following trauma at a Level 1 Trauma Center.: ... ...

Abstract	Objectives: Hemorrhage is a common complication of trauma. We evaluated age and sex differences in treatment with blood product transfusions and massive transfusions as well as in-hospital mortality following trauma at a Level 1 Trauma Center. Methods: This cross-sectional study evaluated trauma data from a Level 1 trauma center registry from January 2013 to December 2017. The primary outcome was amount of blood products (packed red blood cells (PRBCs), plasma, platelets), and massive transfusion (MT) by biological sex and by age group: 16-24 (youth), 25-59 (middle age), and >=60 (older age) The secondary outcome was in-hospital mortality to hospital discharge. Results: There were 13596 trauma patients in the registry, mean age was 48 years, 4589 (34%) female and 9007 (66%) male, and median ISS of 9. Male patients received significantly more PRBC transfusions than female patients within 4-hours 6.6% vs 4.4%, and 24-hours 6.7% vs 4.5% respectively. Older patients received significantly fewer PRBC transfusions within 4-hours and 24-hours than their younger counterparts, with 6.9% in the youth group, 6.8% in the middle age group, and 3.9% in the older group (p<0.001). When adjusted for injury severity, the odds of receiving a blood transfusion within 4 hours of injury was significantly lower in older females. Using multivariate analysis, predictors of mortality included (in order of significance) injury severity, older age, transfusion within 4 hours of injury, penetrating trauma, and male sex. Conclusion: In this large trauma cohort, older female trauma patients were less likely to receive blood products compared to younger females and to their older male counterparts, even after adjusting for injury severity. Predictors of mortality included injury severity, older age, early transfusion, penetrating trauma, and male sex. Following trauma, older women appear vulnerable to undertreatment. Further study is needed to determine the reasons for these differences and their impact on patient outcomes.
Language	English
Publishing date	2023-08-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e18890
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Article: Does a change in end-tidal carbon dioxide level predict high altitude mountain sickness?

Thundiyil, Josef G / Williams, Alex T / Little, Ian / Stutsman, Margaret / Ladde, Jay G / Papa, Linda

Heliyon

2023 Volume 9, Issue 5, Page(s) e16000

Abstract: Background: It is postulated that lack of hypoxic ventilatory response is a predictor for AMS. End-tidal carbon dioxide (ETCO: Objectives: We sought to determine if changes in baseline ETCO: Methods: This prospective cohort study took place in ... ...

Abstract	Background: It is postulated that lack of hypoxic ventilatory response is a predictor for AMS. End-tidal carbon dioxide (ETCO Objectives: We sought to determine if changes in baseline ETCO Methods: This prospective cohort study took place in three separate high-altitude hiking treks. Subjects included a convenience sample of hikers. Predictor variable was change in ETCO Results: 21 subjects in 3 separate hikes participated: 10 ascended to 19,341 ft over 7 days, 6 ascended to 8900 ft in 1 day, and 4 ascended to 11,006 ft in 1 day. Mean age was 40 years, 67% were males, mean daily elevation gain was 2150 ft, and 5 hikers developed AMS. The correlation coefficients for ETCO Conclusions: ETCO
Language	English
Publishing date	2023-05-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e16000
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Article: Is Lateral Decubitus or Upright Positioning Optimal for Lumbar Puncture Success in a Teaching Hospital?

Thundiyil, Josef G / O'Brien, John F / Tymkowicz, Alexandria E / Papa, Linda

The Journal of emergency medicine

2023 Volume 64, Issue 1, Page(s) 14–21

Abstract: Background: Lumbar puncture is a common procedure performed by emergency physicians and trainees. The optimal patient positioning for lumbar puncture procedures has not been studied adequately.: Objectives: We performed a prospective randomized study ...

Abstract	Background: Lumbar puncture is a common procedure performed by emergency physicians and trainees. The optimal patient positioning for lumbar puncture procedures has not been studied adequately. Objectives: We performed a prospective randomized study in an urban, level I academic trauma center. Patients of all ages were included. Patients were randomized to either lateral decubitus or upright positioning. Patient demographic characteristics, level of physician training and experience, number of needle insertions and redirections, need for repositioning, alternative operator use, and laboratory results of the cerebrospinal fluid were recorded. We compared the success rate of each position as our primary outcome measure. We also evaluated number of needle insertions and re-directions and success rates based on experience and patient age. Results: A total of 116 patients were enrolled, with 55 patients assigned to lateral decubitus and 61 to upright position for initial lumbar puncture attempt. Spinal fluid was obtained successfully in 47 of the lateral decubitus group (85.5%; 95% CI 73.8-92.4%) vs. 49 (80.3%; 95% CI 68.7-88.4%) in the upright assignment group. Comparable results were also obtained for first-pass success, number of failures, and number of bloody taps. Postgraduate year 2 residents or those with 31-50 previous lumbar punctures had the highest success rates at 94.3% (95% CI 81.2-98.4%) and 90.3% (95% CI 75.1-96.7%), respectively. Conclusions: Lateral decubitus and upright positioning for emergency lumbar puncture yielded equal success rates in emergency physicians and trainees.
MeSH term(s)	Humans ; Spinal Puncture/methods ; Prospective Studies ; Hospitals, Teaching ; Needles ; Physicians ; Patient Positioning
Language	English
Publishing date	2023-01-12
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	605559-x
ISSN	0736-4679
ISSN	0736-4679
DOI	10.1016/j.jemermed.2022.09.002
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Article ; Online: Does a change in end-tidal carbon dioxide level predict high altitude mountain sickness?

Thundiyil, Josef G. / Williams, Alex T. / Little, Ian / Stutsman, Margaret / Ladde, Jay G. / Papa, Linda

Heliyon. 2023 May, v. 9, no. 5 p.e16000-

2023

Abstract: It is postulated that lack of hypoxic ventilatory response is a predictor for AMS. End-tidal carbon dioxide (ETCO₂) is an accurate, noninvasive surrogate measure of ventilation. We sought to determine if changes in baseline ETCO₂ predicts the development ...

Abstract	It is postulated that lack of hypoxic ventilatory response is a predictor for AMS. End-tidal carbon dioxide (ETCO₂) is an accurate, noninvasive surrogate measure of ventilation. We sought to determine if changes in baseline ETCO₂ predicts the development of AMS. This prospective cohort study took place in three separate high-altitude hiking treks. Subjects included a convenience sample of hikers. Predictor variable was change in ETCO₂ levels and outcome variable was AMS. Measurements of ETCO₂ levels were obtained at the base and repeated daily at various elevations and the summit of each hike. Concurrently, hikers were scored for AMS by a trained investigator. We utilized correlation coefficients and developed a linear regression model for analysis. 21 subjects in 3 separate hikes participated: 10 ascended to 19,341 ft over 7 days, 6 ascended to 8900 ft in 1 day, and 4 ascended to 11,006 ft in 1 day. Mean age was 40 years, 67% were males, mean daily elevation gain was 2150 ft, and 5 hikers developed AMS. The correlation coefficients for ETCO₂ and development of AMS were −0.46 (95%CI -0.33 to −0.57), and −0.77 (95%CI -0.71 to −0.83) for ETCO₂ and altitude. ETCO₂ predicted the development of symptoms better than the elevation with AUCs of 0.90 (95%CI 0.81-0.99) versus 0.64 (95%CI 0.45-0.83). An ETCO₂ measurement of ≤22 mmHg was 100% sensitive and 60% specific for predicting AMS. ETCO₂ was strongly correlated with altitude and moderately correlated with AMS and it was a better predictor than altitude.
Keywords	altitude ; breathing ; carbon dioxide ; cohort studies ; regression analysis ; Altitude illness ; Acute mountain sickness ; End tidal carbon dioxide
Language	English
Dates of publication	2023-05
Publishing place	Elsevier Ltd
Document type	Article ; Online
Note	Use and reproduction
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e16000
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Effect of Player Position on Serum Biomarkers during Participation in a Season of Collegiate Football.

Papa, Linda / Walter, Alexa E / Wilkes, James R / Clonts, Hunter S / Johnson, Brian / Slobounov, Semyon M

Journal of neurotrauma

2022 Volume 39, Issue 19-20, Page(s) 1339–1348

Abstract: This prospective cohort study examined the relationship between a panel of four serum proteomic biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], total Tau, and neurofilament light chain polypeptide [NF-L]) ... ...

Abstract	This prospective cohort study examined the relationship between a panel of four serum proteomic biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], total Tau, and neurofilament light chain polypeptide [NF-L]) in 52 players from two different cohorts of male collegiate student football athletes from two different competitive seasons of Division I National Collegiate Athletic Association Football Bowl Subdivision. This study evaluated changes in biomarker concentrations (as indicators of brain injury) over the course of the playing season (pre- and post-season) and also assessed biomarker concentrations by player position using two different published classification systems. Player positions were divided into: 1) speed (quarterbacks, running backs, halfbacks, fullbacks, wide receivers, tight ends, defensive backs, safety, and linebackers) versus non-speed (offensive and defensive linemen), and 2) "Profile 1" (low frequency/high strain magnitudes positions including quarterbacks, wide receivers, and defensive backs), "Profile 2" (mid-range impact frequency and strain positions including linebackers, running backs, and tight ends), and "Profile 3" (high frequency/low strains positions including defensive and offensive linemen). There were significant increases in GFAP 39.3 to 45.6 pg/mL and NF-L 3.5 to 5.4 pg/mL over the course of the season (
MeSH term(s)	Biomarkers ; Football/injuries ; Glial Fibrillary Acidic Protein ; Humans ; Male ; Prospective Studies ; Proteomics ; Seasons ; Ubiquitin Thiolesterase
Chemical Substances	Biomarkers ; Glial Fibrillary Acidic Protein ; Ubiquitin Thiolesterase (EC 3.4.19.12)
Language	English
Publishing date	2022-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2022.0083
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Article ; Online: Sex Differences in Neurological Emergencies Presenting to Multiple Urban Level 1 Trauma Centers.

Papa, Linda / Cienki, John J / Wilson, Jason W / Axline, Virginia / Coyle, Emily A / Earwood, Ryan C / Thundiyil, Josef G / Ladde, Jay G

Neurotrauma reports

2023 Volume 4, Issue 1, Page(s) 605–612

Abstract: Previous studies have suggested that there are sex differences in the treatment and outcome of neurological emergencies; however, research identifying the role these sex differences play in the management of neurological emergencies is lacking. More ... ...

Abstract	Previous studies have suggested that there are sex differences in the treatment and outcome of neurological emergencies; however, research identifying the role these sex differences play in the management of neurological emergencies is lacking. More knowledge of the way sex factors into the pathophysiology of neurological emergencies will be helpful in improving outcomes for these patients. The aim of this cross-sectional study was to assess the prevalence and management of neurological emergencies while evaluating sex differences in the diagnosis and treatment of these emergencies. We analyzed a cohort of 530 adult patients from four level 1 trauma centers over a period of 4 weeks who had a chief complaint of a neurological emergency, including seizures, cerebrovascular events, headache disorders, traumatic brain injuries, and central nervous system infections. Among patients with neurological emergencies, a significantly lower proportion of female patients underwent neurosurgery and were admitted to the intensive care unit compared to male patients, but there were no significant differences between sexes in the time of symptom onset, type of hospital transportation, amount of neuroimaging performed, admission rates, hospital length of stay, and disposition from the emergency department. Although female patients were more likely to have a chief complaint of headache compared to traumatic injuries in male patients, this was not statistically significant. A significantly higher proportion of female patients had health insurance coverage than male patients.
Language	English
Publishing date	2023-09-12
Publishing country	United States
Document type	Journal Article
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2023.0050
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Article ; Online: Sex differences in time course and diagnostic accuracy of GFAP and UCH-L1 in trauma patients with mild traumatic brain injury.

Papa, Linda / Brophy, Gretchen M / Alvarez, Wilmer / Hirschl, Robert / Cress, Marshall / Weber, Kurt / Giordano, Philip

Scientific reports

2023 Volume 13, Issue 1, Page(s) 11833

Abstract: Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help ... ...

Abstract	Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers' diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. 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-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.
MeSH term(s)	Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Adolescent ; Aged ; Aged, 80 and over ; Sex Characteristics ; Brain Concussion/diagnosis ; Biomarkers
Chemical Substances	GFAP protein, human ; UCHL1 protein, human ; Biomarkers
Language	English
Publishing date	2023-07-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-38804-4
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Article ; Online: End-tidal carbon dioxide measured at emergency department triage outperforms standard triage vital signs in predicting in-hospital mortality and intensive care unit admission.

Ladde, Jay G / Miller, Stacie / Chin, Kevin / Feffer, Cole / Gulenay, George / Kepple, Kirsten / Hunter, Christopher / Thundiyil, Josef G / Papa, Linda

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine

2023 Volume 30, Issue 8, Page(s) 832–841

Abstract: Objectives: This study assessed the ability of end-tidal carbon dioxide (ETCO: Methods: This prospective study enrolled adult patients presenting to the ED of a tertiary care Level I trauma center over 30 months. Patients had standard vital signs ... ...

Abstract	Objectives: This study assessed the ability of end-tidal carbon dioxide (ETCO Methods: This prospective study enrolled adult patients presenting to the ED of a tertiary care Level I trauma center over 30 months. Patients had standard vital signs measured along with exhaled ETCO Results: There were 1136 patients enrolled and 1091 patients with outcome data available. There were 26 (2.4%) patients who did not survive to hospital discharge. Mean ETCO Conclusions: ETCO
MeSH term(s)	Adult ; Humans ; Carbon Dioxide/metabolism ; Triage ; Prospective Studies ; Hospital Mortality ; Vital Signs ; Emergency Service, Hospital ; Intensive Care Units ; Acidosis ; Lactic Acid ; Retrospective Studies
Chemical Substances	Carbon Dioxide (142M471B3J) ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	1329813-6
ISSN	1553-2712 ; 1069-6563
ISSN (online)	1553-2712
ISSN	1069-6563
DOI	10.1111/acem.14703
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