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  1. Article ; Online: In Reply - Hormones and COVID-19.

    MacArthur, Taleen A / Park, Myung S

    Mayo Clinic proceedings

    2023  Volume 98, Issue 7, Page(s) 1099

    MeSH term(s) Humans ; COVID-19 ; Hormones ; SARS-CoV-2
    Chemical Substances Hormones
    Language English
    Publishing date 2023-04-24
    Publishing country England
    Document type Letter
    ZDB-ID 124027-4
    ISSN 1942-5546 ; 0025-6196
    ISSN (online) 1942-5546
    ISSN 0025-6196
    DOI 10.1016/j.mayocp.2023.04.011
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  2. Article ; Online: Plasma thrombin generation kinetics vary by injury pattern and resuscitation characteristics in pediatric and young adult trauma patients.

    MacArthur, Taleen A / Goswami, Julie / Howick, Annelise S / Ramachandran, Dhanya / Polites, Stephanie F / Klinkner, Denise B / Park, Myung S

    The journal of trauma and acute care surgery

    2023  Volume 95, Issue 3, Page(s) 307–312

    Abstract: Background: Thrombin generation kinetics are not well studied in children. This study aimed to assess how thrombin generation kinetics vary in pediatric and young adult (YA) trauma patients by clinical characteristics and injury pattern.: Methods: ... ...

    Abstract Background: Thrombin generation kinetics are not well studied in children. This study aimed to assess how thrombin generation kinetics vary in pediatric and young adult (YA) trauma patients by clinical characteristics and injury pattern.
    Methods: Prospective cohort study where plasma samples were obtained from pediatric (ages 0-17 years) and YA (ages 18-21 years) trauma patients upon emergency department arrival. Thrombin generation (calibrated automated thrombogram [CAT]) was quantified as lag time (LT, minutes), peak height (PH, nM), time to peak (ttPeak, minutes), and endogenous thrombin potential (ETP, nM × minute). Results are expressed as median and quartiles [Q1, Q3] and compared using Wilcoxon rank sum testing with p < 0.05 considered significant.
    Results: We enrolled 47 pediatric (median age, 15 [14, 17] years, 78% male, 87% blunt, median Injury Severity Score, 12) and 49 YA (median age 20 [18, 21] years, 67% male, 84% blunt, median Injury Severity Score, 12) patients. Pediatric and YA patients had similar rates of operative intervention (51% vs. 57%), transfusion (25% vs. 20%), and traumatic brain injury (TBI) (53% vs. 49%). Pediatric patients who required an operation had accelerated initiation of thrombin generation, with shorter LT than those who did not (2.58 [2.33, 2.67]; 2.92 [2.54, 3.00], p = 0.034). Shorter LT (2.41 [2.22, 2.67]; 2.67 [2.53, 3.00]) and ttPeak (4.50 [4.23, 4.73]; 5.22 [4.69, 5.75], both p < 0.01) were noted in pediatric patients who required transfusion as compared with those who did not. The YA patients requiring transfusion had shorter LT (2.33 [2.19, 2.74]; 2.83 [2.67, 3.27]) and ttPeak (4.48 [4.33, 5.65]; 5.33 [4.85, 6.28] both p < 0.04) than those who were not transfused. Young adults with TBI had greater ETP than those without (1509 [1356, 1671]; 1284 [1154, 1471], p = 0.032).
    Conclusion: Thrombin generation kinetics in pediatric trauma patients prior to intervention vary with need for operation and transfusion, while thrombin generation kinetics in young adult patients are influenced by TBI and need for operation or transfusion. This is a promising tool for assessing coagulopathy in young trauma patients.
    Level of evidence: Prognostic and Epidemiological; Level III.
    MeSH term(s) Female ; Humans ; Male ; Blood Coagulation Disorders/complications ; Blood Coagulation Disorders/diagnosis ; Blood Coagulation Tests ; Brain Injuries, Traumatic/blood ; Brain Injuries, Traumatic/complications ; Prospective Studies ; Thrombin/analysis ; Infant, Newborn ; Infant ; Child, Preschool ; Child ; Adolescent ; Young Adult
    Chemical Substances Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2023-03-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2651070-4
    ISSN 2163-0763 ; 2163-0755
    ISSN (online) 2163-0763
    ISSN 2163-0755
    DOI 10.1097/TA.0000000000003901
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  3. Article ; Online: Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity.

    Prior, Shannon M / Park, Myung S / Mann, Kenneth G / Butenas, Saulius

    TH open : companion journal to thrombosis and haemostasis

    2019  Volume 3, Issue 1, Page(s) e10–e19

    Abstract: ... ...

    Abstract Background
    Language English
    Publishing date 2019-01-07
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2901738-5
    ISSN 2512-9465 ; 2567-3459
    ISSN (online) 2512-9465
    ISSN 2567-3459
    DOI 10.1055/s-0038-1677030
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  4. Article ; Online: Inhibitors of Inorganic Polyphosphate and Nucleic Acids Attenuate in vitro Thrombin Generation in Plasma from Trauma Patients.

    MacArthur, Taleen A / Goswami, Julie / Navarro, Sergio M / Vappala, Sreeparna / La, Chanel C / Yudin, Nikoli / Zietlow, John / Smith, Stephanie A / Morrissey, James H / Spears, Grant M / Bailey, Kent R / Dong, Jing-Fei / Kozar, Rosemary A / Kizhakkedathu, Jayachandran N / Park, Myung S

    Shock (Augusta, Ga.)

    2024  

    Abstract: Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8) and universal heparin ...

    Abstract Background: Inorganic polyphosphate (polyP) is a procoagulant polyanion. We assessed the impact of polyP inhibition on thrombin generation after trauma using the novel polyP antagonists, macromolecular polyanion inhibitor 8 (MPI 8) and universal heparin reversal agent 8 (UHRA-8).
    Methods: Plasma thrombin generation (calibrated automated thrombogram, CAT), in 56 trauma patients and 39 controls +/- MPI 8 and UHRA-8 (50 μg/mL), was expressed as lag time (LT, minutes), peak height (PH, nM), and time to peak (ttPeak, minutes), with change in LT (ΔLT) and change in ttPeak (ΔttPeak) quantified. Results expressed in median and quartiles [Q1, Q3], Wilcoxon matched-pairs testing, p < 0.05 significant.
    Results: Trauma patients had greater baseline PH than controls (182.9 [121.0, 255.2]; 120.5 [62.1, 174.8], p < 0.001). MPI 8 treatment prolonged LT and ttPeak in trauma (7.20 [5.88, 8.75]; 6.46 [5.45, 8.93], p = 0.020; 11.28 [8.96, 13.14]; 11.00 [8.95, 12.94], p = 0.029) and controls (7.67 [6.67, 10.50]; 6.33 [5.33, 8.00], p < 0.001; 13.33 [11.67, 15.33]; 11.67 [10.33, 13.33], p < 0.001). UHRA-8 treatment prolonged LT and ttPeak and decreased PH in trauma (9.09 [7.45, 11.33]; 6.46 [5.45, 8.93]; 14.02 [11.78, 17.08]; 11.00 [8.95, 12.94]; 117.4 [74.5, 178.6]; 182.9 [121.0, 255.2]) and controls (9.83 [8.00, 12.33]; 6.33 [5.33, 8.00]; 16.67 [14.33, 20.00]; 11.67 [10.33, 13.33]; 55.3 [30.2, 95.9]; 120.5 [62.1, 174.8]), all p < 0.001. Inhibitor effects were greater for controls (greater ΔLT and ΔttPeak for both inhibitors, p < 0.001).
    Conclusion: PolyP inhibition attenuates thrombin generation, though to a lesser degree in trauma than in controls, suggesting that polyP contributes to accelerated thrombin generation after trauma.
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1185432-7
    ISSN 1540-0514 ; 1073-2322
    ISSN (online) 1540-0514
    ISSN 1073-2322
    DOI 10.1097/SHK.0000000000002362
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  5. Article ; Online: A murine multiple-injury model for the study of thromboinflammation.

    MacArthur, Taleen A / Goswami, Julie / Navarro, Sergio M / Spears, Grant M / Bailey, Kent R / Thompson, Riley / Dong, Jing-Fei / Kozar, Rosemary A / Auton, Matthew T / Knight, Jason / Park, Myung S

    The journal of trauma and acute care surgery

    2023  Volume 96, Issue 2, Page(s) 203–208

    Abstract: Introduction: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation.: ... ...

    Abstract Introduction: Neutrophil extracellular traps (NETs) contribute to trauma-induced coagulopathy. We aimed to develop a murine multiple-injury model that induces thrombo-inflammatory response, that is, NETosis and accelerated thrombin generation.
    Methods: Wild-type male mice (n = 10, aged 8-12 weeks) underwent multiple injuries (gastrocnemius crush, femur fracture, and laparotomy) and were compared with an uninjured control group (n = 10). Mice were euthanized by cardiac puncture performed 3 hours after injury. Whole blood samples were immediately processed to platelet poor plasma for thrombin generation kinetics (calibrated automated thrombogram), myeloperoxidase (MPO), and von Willebrand factor quantification. Immunohistochemistry of lung tissue was performed to assess for citrullinated histone 3 (CitH3) and MPO. A NETosis cluster was defined as 3+ neutrophils staining for CitH3 at 400× magnification (CitH3 cluster). Data were presented either as mean (SD) or median (interquartile range) with p < 0.05 significant. Sham and trauma treated animals were compared by the two-sample Wilcoxon rank-sum test.
    Results: Animals subjected to multiple injuries had accelerated thrombin generation compared with controls with greater peak height (61.3 [41.2-73.2] vs. 28.4 [19.5-37.5] nM, p = 0.035) and shorter time to peak (3.37 [2.81-3.81] vs. 4.5 [4.08-4.75] minutes, p = 0.046). Markers of neutrophil activation were greater following multiple injuries than in controls (MPO, 961.1 [858.1-1116.8] vs. 481.3 [438.0-648.9] ng/mL; p = 0.004). NETosis, as evidenced by the aforementioned defined number of CitH3 clusters in the lung, was greater in multiple-injury animals than in controls (mean [SD], 3 [2.9] vs. 0.2 [0.7]; p = 0.009).
    Conclusion: This is the first study to demonstrate that NETosis and accelerated thrombin generation can be induced using a murine multiple-injury model, as early as 3 hours following injury.
    MeSH term(s) Male ; Mice ; Animals ; Thromboinflammation ; Inflammation ; Thrombin ; Thrombosis ; Multiple Trauma ; Neutrophils ; Histones
    Chemical Substances Thrombin (EC 3.4.21.5) ; Histones
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2651070-4
    ISSN 2163-0763 ; 2163-0755
    ISSN (online) 2163-0763
    ISSN 2163-0755
    DOI 10.1097/TA.0000000000004179
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  6. Article: Subjectivity in fair-value estimates, audit quality, and informativeness of other comprehensive income

    Lee, Cheol / Park, Myung S

    Advances in accounting : a research annual Vol. 29, No. 2 , p. 218-231

    2013  Volume 29, Issue 2, Page(s) 218–231

    Author's details Cheol Lee; Myung S. Park
    Language English
    Publisher Elsevier
    Publishing place Amsterdam [u.a.]
    Document type Article
    ZDB-ID 722244-0
    ISSN 0882-6110
    Database ECONomics Information System

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  7. Article ; Online: Estradiol and Dihydrotestosterone Levels in COVID-19 Patients.

    MacArthur, Taleen A / Goswami, Julie / Ramachandran, Dhanya / Price-Troska, Tammy L / Lundell, Kaitlin A / Ballinger, Beth A / Loomis, Erica A / Heller, Stephanie F / Stephens, Daniel / Hurt, Ryan T / Salonen, Bradley R / Ganesh, Ravindra / Spears, Grant M / Bailey, Kent R / Chaudry, Irshad H / Park, Myung S

    Mayo Clinic proceedings

    2023  Volume 98, Issue 4, Page(s) 559–568

    Abstract: Objective: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the ... ...

    Abstract Objective: To determine differences in plasma sex hormone levels in male and female coronavirus disease 2019 (COVID-19) patients and healthy volunteers (HVs) because cell entry of severe acute respiratory syndrome coronavirus 2 occurs via the angiotensin-converting enzyme 2 receptor which is downregulated by 17β-estradiol.
    Patients and methods: Citrated plasma samples were collected from 101 patients with COVID-19 upon presentation to the emergency department and from 40 HVs between November 1, 2020, and May 30, 2021. Plasma 17β-estradiol and 5α-dihydrotestosterone (DHT) levels were measured using enzyme-linked immunosorbent assay (pg/mL). Data are presented as median and quartiles (IQR). Wilcoxon rank sum test with a P value less than .05 was considered significant.
    Results: Patients with COVID-19 (median age, 49 years) included 51 males and 50 females (25 postmenopausal). Hospital admission was required for 58.8% of male patients (n = 30) and 48.0% of female patients (n = 24) (66.7% postmenopausal, n = 16) Healthy volunteers (median age, 41 years) included 20 males and 20 females (9 postmenopausal). Female patients with COVID-19 were found to have decreased 17β-estradiol levels (18.5 [IQR, 10.5-32.3] pg/mL; 41.4 [IQR, 15.5-111.0] pg/mL, P=.025), and lower 17β-estradiol to DHT ratios (0.073 [IQR, 0.052-0.159] pg/mL; 0.207 [IQR, 0.104-0.538] pg/mL, P=.015) than female HVs. Male patients with COVID-19 were found to have decreased DHT levels (302.8 [IQR, 249.9-470.8] pg/mL; 457.2 [IQR, 368.7-844.3] pg/mL, P=.005), compared with male HVs. Levels of DHT did not differ between female patients with COVID-19 and female HVs, whereas 17β-estradiol levels did not differ between male patients with COVID-19 and male HVs.
    Conclusion: Sex hormone levels differ between patients with COVID-19 and HVs, with sex-specific patterns of hypogonadism in males and females. These alterations may be associated with disease development and severity.
    MeSH term(s) Humans ; Male ; Female ; Middle Aged ; Adult ; Estradiol ; Dihydrotestosterone ; COVID-19 ; Testosterone
    Chemical Substances Estradiol (4TI98Z838E) ; Dihydrotestosterone (08J2K08A3Y) ; Testosterone (3XMK78S47O)
    Language English
    Publishing date 2023-01-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 124027-4
    ISSN 1942-5546 ; 0025-6196
    ISSN (online) 1942-5546
    ISSN 0025-6196
    DOI 10.1016/j.mayocp.2022.12.018
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  8. Article: Endogenous Procoagulant Activity in Trauma Patients and Its Relationship to Trauma Severity

    Prior, Shannon M. / Park, Myung S. / Mann, Kenneth G. / Butenas, Saulius

    TH Open

    2019  Volume 03, Issue 01, Page(s) e10–e19

    Abstract: Background: It has been observed that trauma patients have elevated plasma procoagulant activity that could be assigned to an elevated concentration of tissue factor (TF). However, in many instances there is a discrepancy between the levels of TF and ... ...

    Abstract Background: It has been observed that trauma patients have elevated plasma procoagulant activity that could be assigned to an elevated concentration of tissue factor (TF). However, in many instances there is a discrepancy between the levels of TF and the procoagulant activity observed. We hypothesized that factor XIa (FXIa) could be responsible for this additional activity and that the presence and levels of both proteins could correlate with trauma severity.
    Methods: Citrate plasma from 98 trauma patients (47 blunt, 17 penetrating, and 34 thermal) were evaluated in clotting assays for the presence of FXIa and TF activity using respective inhibitory antibodies.
    Results: When the three trauma patient groups were divided into two cohorts (Injury Severity Score [ISS] > 25 and ISS ≤ 25), higher frequencies and concentrations of both TF and FXIa were observed for all the more severe injury subgroups.
    Conclusions: The majority of trauma patients have active FXIa in their plasma, with a significant fraction having active TF as well. Additionally, both TF and FXIa frequency and concentration directly relate to trauma severity. These data suggest the use of these two proteins as potential markers for the stratification of trauma patients.
    Keywords factor XIa activity ; tissue factor activity ; severity of trauma ; markers of trauma
    Language English
    Publishing date 2019-01-01
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 2901738-5
    ISSN 2512-9465 ; 2567-3459
    ISSN (online) 2512-9465
    ISSN 2567-3459
    DOI 10.1055/s-0038-1677030
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  9. Article ; Online: A Review of Pathophysiology, Clinical Features, and Management Options of COVID-19 Associated Coagulopathy.

    Goswami, Julie / MacArthur, Taleen A / Sridharan, Meera / Pruthi, Rajiv K / McBane, Robert D / Witzig, Thomas E / Park, Myung S

    Shock (Augusta, Ga.)

    2020  Volume 55, Issue 6, Page(s) 700–716

    Abstract: Abstract: There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed "COVID-19 associated coagulopathy." COVID-19 has been associated with increased rates of both venous and ... ...

    Abstract Abstract: There is increasing evidence that novel coronavirus disease 2019 (COVID-19) leads to a significant coagulopathy, a phenomenon termed "COVID-19 associated coagulopathy." COVID-19 has been associated with increased rates of both venous and arterial thromboembolic events, a source of significant morbidity and mortality in this disease. Further evidence suggests a link between the inflammatory response and coagulopathy associated with COVID-19. This presents a unique set of challenges for diagnosis, prevention, and treatment of thrombotic complications. In this review, we summarize and discuss the current literature on laboratory coagulation disruptions associated with COVID-19 and the clinical effects of thromboembolic events including pulmonary embolism, deep vein thrombosis, peripheral arterial thrombosis, and acute ischemic stroke in COVID-19. Endothelial injury and augmented innate immune response are implicated in the development of diffuse macro- and microvascular thrombosis in COVID-19. The pathophysiology of COVID-19 associated coagulopathy is an important determinant of appropriate treatment and monitoring of these complications. We highlight the importance of diagnosis and management of dysregulated coagulation in COVID-19 to improve outcomes in COVID-19 patients with thromboembolic complications.
    MeSH term(s) Blood Coagulation/immunology ; Blood Coagulation Disorders/etiology ; Blood Coagulation Disorders/immunology ; Blood Coagulation Disorders/pathology ; Blood Coagulation Disorders/therapy ; COVID-19/complications ; COVID-19/pathology ; COVID-19/therapy ; Humans ; Immunity, Innate ; Ischemic Stroke/complications ; Ischemic Stroke/metabolism ; Ischemic Stroke/pathology ; Pulmonary Embolism/etiology ; Pulmonary Embolism/immunology ; Pulmonary Embolism/pathology ; Pulmonary Embolism/therapy ; SARS-CoV-2/immunology ; Thrombosis/etiology ; Thrombosis/immunology ; Thrombosis/pathology ; Thrombosis/therapy
    Language English
    Publishing date 2020-11-06
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Systematic Review
    ZDB-ID 1185432-7
    ISSN 1540-0514 ; 1073-2322
    ISSN (online) 1540-0514
    ISSN 1073-2322
    DOI 10.1097/SHK.0000000000001680
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  10. Article ; Online: Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.

    Moore, Hunter B / Neal, Matthew D / Bertolet, Marnie / Joughin, Brian A / Yaffe, Michael B / Barrett, Christopher D / Bird, Molly A / Tracy, Russell P / Moore, Ernest E / Sperry, Jason L / Zuckerbraun, Brian S / Park, Myung S / Cohen, Mitchell J / Wisniewski, Stephen R / Morrissey, James H

    Annals of surgery open : perspectives of surgical history, education, and clinical approaches

    2022  Volume 3, Issue 2

    Abstract: Objective: Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically ... ...

    Abstract Objective: Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgement) are sufficient to capture the majority of protein changes associated with MT.
    Methods: Eight level-I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR >1.5 (INR-TIC), TEG maximum amplitude <50mm (TEG-TIC), or clinical judgement (Clin-TIC) by the trauma surgeon. MT was defined as > 10 units of red blood cells in 24 hours or > 4 units RBC/hour during the first 4 hr. SomaLogic proteomic analysis of 1,305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified.
    Results: Patients (n=211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway.
    Conclusion: These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.
    Language English
    Publishing date 2022-05-25
    Publishing country United States
    Document type Journal Article
    ISSN 2691-3593
    ISSN (online) 2691-3593
    DOI 10.1097/as9.0000000000000167
    Database MEDical Literature Analysis and Retrieval System OnLINE

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