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  1. AU="Fortin, Brooke"
  2. AU="Joana Martins"
  3. AU="Arnalich Fernández, Francisco"
  4. AU="Casado Lopez, Irene"
  5. AU="Payaningal R. Somanath"
  6. AU=Das Ananya
  7. AU="Dave, Riya"
  8. AU=Kwon Okyu
  9. AU="Ortiz-López, Francisco Javier"
  10. AU="Churiwal, Mehal"
  11. AU="Nandi, Asoke K"
  12. AU="Fishchenko, I"
  13. AU="Yong, Ken-Tye"
  14. AU="Alexander, Regi T"
  15. AU=Weng Cheng-Hao
  16. AU="Christine Hamel"

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  1. Artikel ; Online: Assessment of Temporary Warfarin Reversal in Patients With Left Ventricular Assist Devices: the KVAD Study.

    Sylvester, Katelyn W / Grandoni, Jessica / Rhoten, Megan / Coakley, Lara / Matiello-Lyons, Erin / Frankel, Katie / Fortin, Brooke / Jolley, Kate / Park, Hae Soo / Freedman, Revital Y / Mehra, Mandeep R / Givertz, Michael M / Connors, Jean M

    Journal of cardiac failure

    2024  

    Abstract: Background: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can ... ...

    Abstract Background: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin.
    Objectives: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed.
    Methods: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected.
    Results: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4).
    Conclusion: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events.
    Sprache Englisch
    Erscheinungsdatum 2024-03-21
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 1281194-4
    ISSN 1532-8414 ; 1071-9164
    ISSN (online) 1532-8414
    ISSN 1071-9164
    DOI 10.1016/j.cardfail.2024.02.022
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Sudden death in sickle cell disease: current experience.

    Nze, Chijioke / Fortin, Brooke / Freedman, Revital / Mandell, Elyse / Puligandla, Maneka / Neuberg, Donna / Achebe, Maureen

    British journal of haematology

    2019  Band 188, Heft 4, Seite(n) e43–e45

    Mesh-Begriff(e) Adolescent ; Adult ; Aged ; Anemia, Sickle Cell/mortality ; Child ; Child, Preschool ; Death, Sudden ; Female ; Humans ; Infant ; Male ; Middle Aged ; Retrospective Studies
    Sprache Englisch
    Erscheinungsdatum 2019-12-05
    Erscheinungsland England
    Dokumenttyp Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.16314
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: CYP46A1 activation by low-dose efavirenz enhances brain cholesterol metabolism in subjects with early Alzheimer's disease.

    Lerner, Alan J / Arnold, Steven E / Maxfield, Erin / Koenig, Aaron / Toth, Maria E / Fortin, Brooke / Mast, Natalia / Trombetta, Bianca A / Denker, John / Pieper, Andrew A / Tatsuoka, Curtis / Raghupathy, Sangeetha / Pikuleva, Irina A

    Alzheimer's research & therapy

    2022  Band 14, Heft 1, Seite(n) 198

    Abstract: Background: Efavirenz is an anti-HIV drug, and cytochrome P450 46A1 (CYP46A1) is a CNS-specific enzyme that metabolizes cholesterol to 24-hydroxycholesterol (24HC). We have previously shown that allosteric CYP46A1 activation by low-dose efavirenz in a ... ...

    Abstract Background: Efavirenz is an anti-HIV drug, and cytochrome P450 46A1 (CYP46A1) is a CNS-specific enzyme that metabolizes cholesterol to 24-hydroxycholesterol (24HC). We have previously shown that allosteric CYP46A1 activation by low-dose efavirenz in a transgenic mouse model of Alzheimer's disease (AD) enhanced both cholesterol elimination and turnover in the brain and improved animal performance in memory tests. Here, we sought to determine whether CYP46A1 could be similarly activated by a low-dose efavirenz in human subjects.  METHODS: This pilot study enrolled 5 subjects with early AD. Participants were randomized to placebo (n = 1) or two daily efavirenz doses (50 mg and 200 mg, n = 2 for each) for 20 weeks and evaluated for safety and CYP46A1 target engagement (plasma 24HC levels). A longitudinal mixed model was used to ascertain the statistical significance of target engagement. We also measured 24HC in CSF and conducted a unique stable isotope labeling kinetics (SILK) study with deuterated water to directly measure CYP46A1 activity changes in the brain.
    Results: In subjects receiving efavirenz, there was a statistically significant within-group increase (P ≤ 0.001) in the levels of plasma 24HC from baseline. The levels of 24HC in the CSF of subjects on the 200-mg dose of efavirenz were also increased. Target engagement was further supported by the labeling kinetics of 24HC by deuterated water in the SILK study. There were no serious adverse effects in any subjects.
    Conclusions: Our findings suggest efavirenz target engagement in human subjects with early AD. This supports the pursuit of a larger trial for further determination and confirmation of the efavirenz dose that exerts maximal enzyme activation, as well as evaluation of this drug's effects on AD biomarkers and clinical symptomatology.
    Trial registration: ClinicalTrials.gov, NCT03706885.
    Mesh-Begriff(e) Humans ; Alzheimer Disease/metabolism ; Brain/metabolism ; Cholesterol ; Cholesterol 24-Hydroxylase/metabolism ; Cholesterol 24-Hydroxylase/therapeutic use ; Pilot Projects
    Chemische Substanzen Cholesterol (97C5T2UQ7J) ; Cholesterol 24-Hydroxylase (EC 1.14.14.25) ; efavirenz (JE6H2O27P8)
    Sprache Englisch
    Erscheinungsdatum 2022-12-29
    Erscheinungsland England
    Dokumenttyp Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-022-01151-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: CD4+ T-cell lymphopenia in frequent platelet donors who have ceased platelet donation for at least 1 year.

    Rahmani, Mahboubeh / Fortin, Brooke M / Berliner, Nancy / Issa, Nicolas / Neuberg, Donna / Kaufman, Richard M / Gansner, John M

    Transfusion

    2019  Band 59, Heft 5, Seite(n) 1644–1647

    Abstract: Background: We recently discovered that 30% of current frequent apheresis platelet donors in a study at our donor center had CD4+ counts below 200 cells/μL. How long CD4+ lymphopenia persists after ceasing plateletpheresis is unknown. Whether there are ... ...

    Abstract Background: We recently discovered that 30% of current frequent apheresis platelet donors in a study at our donor center had CD4+ counts below 200 cells/μL. How long CD4+ lymphopenia persists after ceasing plateletpheresis is unknown. Whether there are infectious or other complications in former frequent donors that could relate to CD4+ lymphopenia is also unknown.
    Study design and methods: We mailed a letter to former frequent apheresis platelet donors who had not donated platelets for at least 12 months. Frequent donation was defined as 20 to 24 plateletpheresis sessions in at least one 365-day period starting in 2011. Donors who expressed interest in the study were contacted to schedule a study visit. Participants in the study provided a blood sample and completed a health questionnaire that included questions about opportunistic infections and malignancies.
    Results: Of 50 potential study candidates who were mailed a letter, 15 participated in the study. There were 2 participants with CD4+ counts below 200 cells/μL, one of whom had prior counts that documented a small improvement with cessation of plateletpheresis. Three participants had counts between 200 and 300 cells/μL. No study participant had a history of an opportunistic infection or a malignancy associated with immune dysregulation.
    Conclusion: We detected CD4+ lymphopenia in former frequent apheresis platelet donors who had ceased platelet donation for more than 1 year. There was no evidence that the CD4+ lymphopenia predisposes to opportunistic infections or to malignancies associated with immune dysregulation.
    Mesh-Begriff(e) Adult ; Aged ; Blood Donors ; Blood Platelets/metabolism ; CD4-Positive T-Lymphocytes/metabolism ; Female ; Humans ; Lymphopenia/metabolism ; Lymphopenia/therapy ; Male ; Middle Aged ; Platelet Count ; Plateletpheresis/methods
    Sprache Englisch
    Erscheinungsdatum 2019-02-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.15192
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Plateletpheresis-associated lymphopenia in frequent platelet donors.

    Gansner, John M / Rahmani, Mahboubeh / Jonsson, A Helena / Fortin, Brooke M / Brimah, Idayat / Ellis, Martha / Smeland-Wagman, Robin / Li, Zhihan J / Schenkel, Jason M / Brenner, Michael B / Yefidoff-Freedman, Revital / Sloan, Steven R / Berliner, Nancy / Issa, Nicolas C / Baden, Lindsey R / Longo, Dan L / Wesemann, Duane R / Neuberg, Donna / Rao, Deepak A /
    Kaufman, Richard M

    Blood

    2018  Band 133, Heft 6, Seite(n) 605–614

    Abstract: More than 1 million apheresis platelet collections are performed annually in the United States. After 2 healthy plateletpheresis donors were incidentally found to have low ... ...

    Abstract More than 1 million apheresis platelet collections are performed annually in the United States. After 2 healthy plateletpheresis donors were incidentally found to have low CD4
    Mesh-Begriff(e) Adult ; Aged ; Blood Donors/statistics & numerical data ; Blood Platelets/cytology ; Cross-Sectional Studies ; Female ; Humans ; Lymphopenia/etiology ; Male ; Middle Aged ; Platelet Count ; Plateletpheresis/adverse effects ; Prognosis ; Young Adult
    Sprache Englisch
    Erscheinungsdatum 2018-11-14
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2018-09-873125
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Correction to: Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2.

    Trombetta, Bianca A / Kandigian, Savannah E / Kitchen, Robert R / Grauwet, Korneel / Webb, Pia Kivisäkk / Miller, Glenn A / Jennings, Charles G / Jain, Sejal / Miller, Samara / Kuo, Yikai / Sweeney, Thadryan / Gilboa, Tal / Norman, Maia / Simmons, Daimon P / Ramirez, Christopher E / Bedard, Melissa / Fink, Catherine / Ko, Jina / De León Peralta, Esmarline J /
    Watts, Gerald / Gomez-Rivas, Emma / Davis, Vannessa / Barilla, Rocky M / Wang, Jianing / Cunin, Pierre / Bates, Samuel / Morrison-Smith, Chevaun / Nicholson, Benjamin / Wong, Edmond / El-Mufti, Leena / Kann, Michael / Bolling, Anna / Fortin, Brooke / Ventresca, Hayden / Zhou, Wen / Pardo, Santiago / Kwock, Megan / Hazra, Aditi / Cheng, Leo / Ahmad, Q Rushdy / Toombs, James A / Larson, Rebecca / Pleskow, Haley / Luo, Nell Meosky / Samaha, Christina / Pandya, Unnati M / De Silva, Pushpamali / Zhou, Sally / Ganhadeiro, Zakary / Yohannes, Sara / Gay, Rakiesha / Slavik, Jacqueline / Mukerji, Shibani S / Jarolim, Petr / Walt, David R / Carlyle, Becky C / Ritterhouse, Lauren L / Suliman, Sara

    BMC infectious diseases

    2021  Band 21, Heft 1, Seite(n) 628

    Sprache Englisch
    Erscheinungsdatum 2021-07-01
    Erscheinungsland England
    Dokumenttyp Published Erratum
    ISSN 1471-2334
    ISSN (online) 1471-2334
    DOI 10.1186/s12879-021-06333-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2.

    Trombetta, Bianca A / Kandigian, Savannah E / Kitchen, Robert R / Grauwet, Korneel / Webb, Pia Kivisäkk / Miller, Glenn A / Jennings, Charles G / Jain, Sejal / Miller, Samara / Kuo, Yikai / Sweeney, Thadryan / Gilboa, Tal / Norman, Maia / Simmons, Daimon P / Ramirez, Christopher E / Bedard, Melissa / Fink, Catherine / Ko, Jina / De León Peralta, Esmarline J /
    Watts, Gerald / Gomez-Rivas, Emma / Davis, Vannessa / Barilla, Rocky M / Wang, Jianing / Cunin, Pierre / Bates, Samuel / Morrison-Smith, Chevaun / Nicholson, Benjamin / Wong, Edmond / El-Mufti, Leena / Kann, Michael / Bolling, Anna / Fortin, Brooke / Ventresca, Hayden / Zhou, Wen / Pardo, Santiago / Kwock, Megan / Hazra, Aditi / Cheng, Leo / Ahmad, Q Rushdy / Toombs, James A / Larson, Rebecca / Pleskow, Haley / Luo, Nell Meosky / Samaha, Christina / Pandya, Unnati M / De Silva, Pushpamali / Zhou, Sally / Ganhadeiro, Zakary / Yohannes, Sara / Gay, Rakiesha / Slavik, Jacqueline / Mukerji, Shibani S / Jarolim, Petr / Walt, David R / Carlyle, Becky C / Ritterhouse, Lauren L / Suliman, Sara

    BMC infectious diseases

    2021  Band 21, Heft 1, Seite(n) 580

    Abstract: Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of ... ...

    Abstract Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed.
    Methods: We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays' performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence.
    Results: Combined IgG + IgM sensitivities ranged from 33.9 to 94.6%, while combined specificities ranged from 92.6 to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG + IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG + IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 μg/mL), followed by a similar LOD of 1.5 μg/mL for CareHealth, Cellex, KHB, and Vivachek.
    Conclusion: We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.
    Mesh-Begriff(e) Adult ; Aged ; Antibodies, Viral/blood ; COVID-19/blood ; COVID-19/diagnosis ; COVID-19 Serological Testing/methods ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Limit of Detection ; Male ; Middle Aged ; Predictive Value of Tests ; Prevalence ; SARS-CoV-2/immunology ; Sensitivity and Specificity ; User-Centered Design ; User-Computer Interface
    Chemische Substanzen Antibodies, Viral ; Immunoglobulin G ; Immunoglobulin M
    Sprache Englisch
    Erscheinungsdatum 2021-06-16
    Erscheinungsland England
    Dokumenttyp Journal Article
    ZDB-ID 2041550-3
    ISSN 1471-2334 ; 1471-2334
    ISSN (online) 1471-2334
    ISSN 1471-2334
    DOI 10.1186/s12879-021-06257-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2

    Trombetta, Bianca A. / Kandigian, Savannah E. / Kitchen, Robert R. / Grauwet, Korneel / Webb, Pia Kivisakk / Miller, Glenn A / Jennings, Charles G. / Jain, Sejal / Miller, Samara Maxine / Kuo, Yikai / Sweeney, Thadryan / Gilboa, Tal / Norman, Maia / Simmons, Daimon P / Ramirez, Christopher E. / Bedard, Melissa / Fink, Catherine / Ko, Jina / Peralta, Esmarline J. De Leon /
    Watts, Gerald / Gomez-Rivas, Emma / Davis, Vannessa / Barilla, Rocky / Wang, Jianing / Cunin, Pierre / Bates, Samuel / Morrison-Smith, Chevaun / Nicholson, Benjamin / Wong, Edmond / El-Mufti, Leena / Kann, Michael / Bolling, Anna / Fortin, Brooke / Ventresca, Hayden / Zhou, Wen / Pardo, Santiago / Kwock, Megan / Hazra, Aditi / Cheng, Leo / Ahmad, Rushdy / Toombs, James A. / Larson, Rebecca / Pleskow, Haley / Luo, Nell Meosky / Samaha, Christina / Pandya, Unnati M. / De Silva, Pushpamali / Zhou, Sally / Ganhadeiro, Zakary / Yohannes, Sara / Gay, Rakiesha / Slavik, Jacqueline / Mukerji, Shibani S. / Jarolim, Petr / Walt, David R. / Carlyle, Becky C. / Ritterhouse, Lauren L. / Suliman, Sara

    medRxiv

    Abstract: Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of ... ...

    Abstract Background: COVID-19 has resulted in significant morbidity and mortality worldwide. Lateral flow assays can detect anti-Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) antibodies to monitor transmission. However, standardized evaluation of their accuracy and tools to aid in interpreting results are needed. Methods: We evaluated 20 IgG and IgM assays selected from available tests in April 2020. We evaluated the assays performance using 56 pre-pandemic negative and 56 SARS-CoV-2-positive plasma samples, collected 10-40 days after symptom onset, confirmed by a molecular test and analyzed by an ultra-sensitive immunoassay. Finally, we developed a user-friendly web app to extrapolate the positive predictive values based on their accuracy and local prevalence. Results: Combined IgG+IgM sensitivities ranged from 33.9% to 94.6%, while combined specificities ranged from 92.6% to 100%. The highest sensitivities were detected in Lumiquick for IgG (98.2%), BioHit for both IgM (96.4%), and combined IgG+IgM sensitivity (94.6%). Furthermore, 11 LFAs and 8 LFAs showed perfect specificity for IgG and IgM, respectively, with 15 LFAs showing perfect combined IgG+IgM specificity. Lumiquick had the lowest estimated limit-of-detection (LOD) (0.1 μg/mL), followed by a similar LOD of 1.5 μg/mL for CareHealth, Cellex, KHB, and Vivachek. Conclusion: We provide a public resource of the accuracy of select lateral flow assays with potential for home testing. The cost-effectiveness, scalable manufacturing process, and suitability for self-testing makes LFAs an attractive option for monitoring disease prevalence and assessing vaccine responsiveness. Our web tool provides an easy-to-use interface to demonstrate the impact of prevalence and test accuracy on the positive predictive values.
    Schlagwörter covid19
    Sprache Englisch
    Erscheinungsdatum 2021-01-04
    Verlag Cold Spring Harbor Laboratory Press
    Dokumenttyp Artikel ; Online
    DOI 10.1101/2021.01.02.20248998
    Datenquelle COVID19

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