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1. A comparison of quality-adjusted life years in older adults after heart transplantation versus long-term mechanical support: Findings from the SUSTAIN-IT study

Author

Grady, Kathleen L., Dew, Mary Amanda, Pagani, Francis D., Spertus, John A., Hsich, Eileen, Yuzefpolskaya, Melana, Lampert, Brent, Kirklin, James K., Petty, Michael, Kao, Andrew, Yancy, Clyde, Hartupee, Justin, Pamboukian, Salpy V., Johnson, Maryl, Murray, Margaret, Wu, Tingqing, and Andrei, Adin-Cristian

Published
2024
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2. Caregiver burden before heart transplantation and long-term mechanical circulatory support: Findings from the sustaining quality of life of the aged: Transplant or mechanical support (SUSTAIN-IT) study

Author

Okwuosa, Ike S., Anderson, Allen, Petty, Michael, Wu, Tingqing, Andrei, Adin-Cristian, Kao, Andrew, Spertus, John A., Pham, Duc T., Yancy, Clyde W., Dew, Mary Amanda, Hsich, Eileen, Cotts, William, Hartupee, Justin, Pamboukian, Salpy, Pagani, Francis, Lampert, Brent, Johnson, Maryl, Murray, Margaret, Tekeda, Koji, Yuzefpolskaya, Melana, Kirklin, James K., and Grady, Kathleen L.

Published
2023
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3. Change in Caregiver Health-Related Quality of Life From Before to Early After Surgery: SUSTAIN-IT Study

Author

Chuzi, Sarah, Wilcox, Jane E., Kao, Andrew, Spertus, John A., Hsich, Eileen, Dew, Mary Amanda, Yancy, Clyde W., Pham, Duc T., Hartupee, Justin, Petty, Michael, Cotts, William, Pamboukian, Salpy V., Pagani, Francis D., Lampert, Brent, Johnson, Maryl, Murray, Margaret, Takeda, Koji, Yuzefpolskaya, Melana, Silvestry, Scott, Kirklin, James K., Wu, Tingqing, Andrei, Adin-Cristian, Baldridge, Abigail, and Grady, Kathleen L.

Published
2023
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7. Abstract 13701: Change in Caregiver Burden From Before to 1 Year After Surgery: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (Sustain-IT) Study

Author

Okwuosa, Ike, Andrei, Adin-cristian, Liu, Menghan, PETTY, Michael G, Hsich, Eileen M, Dew, Mary Amanda, sciortino, christopher, Pham, Duc T, Yancy, Clyde W, Warzecha, Anna, HARTUPEE, Justin, Cotts, William, Pamboukian, Salpy, Pagani, Francis D, Lampert, Brent, Johnson, Maryl R, Murray, Margaret, Takeda, Koji, yuzefpolskaya, melana, Silvestry, Scott C, Spertus, John A, Kirklin, James K, Collum, Craig, and Grady, Kathleen L

Published
2020
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8. Abstract 13558: Caregiver Anxiety Reduced From Baseline to 12 Months After Surgery: Findings From the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Circulatory Support (Sustain-it) Study

Author

Petty, Michael, Andrei, Adin-Cristian, Elenbaas, Christian, Warzecha, Anna, Yancy, Clyde, Pham, Duc, Kao, Andrew, Spertus, John, Hsich, Eileen M, Dew, Mary Amanda, Sciortino, Christopher, HARTUPEE, Justin, Cotts, William, Pamboukian, Salpy, Pagani, Francis D, Lampert, Brent, Johnson, Maryl R, Murray, Margaret A, Takeda, Koji, Yusefpolskaya, Melana, Silvestry, Scott, Kirklin, James, Collum, Craig, and Grady, Kathleen L

Published
2020
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9. Dapagliflozin Effects on Biomarkers, Symptoms, and Functional Status in Patients With Heart Failure With Reduced Ejection Fraction: The DEFINE-HF Trial

Author

Nassif, Michael E., Windsor, Sheryl L., Tang, Fengming, Khariton, Yevgeniy, Husain, Mansoor, Inzucchi, Silvio E., McGuire, Darren K., Pitt, Bertram, Scirica, Benjamin M., Austin, Bethany, Drazner, Mark H., Fong, Michael W., Givertz, Michael M., Gordon, Robert A., Jermyn, Rita, Katz, Stuart D., Lamba, Sumant, Lanfear, David E., LaRue, Shane J., Lindenfeld, JoAnn, Malone, Michael, Margulies, Kenneth, Mentz, Robert J., Mutharasan, R. Kannan, Pursley, Michael, Umpierrez, Guillermo, Kosiborod, Mikhail, Malik, Ali O., Wenger, Nannette, Ogunniyi, Modele, Vellanki, Priyathama, Murphy, Brenda, Newman, Jonathan, Hartupee, Justin, Gupta, Charu, Goldsmith, Marcela, Baweja, Paramdeep, Montero, Manuel, Gottlieb, Stephen S., Costanzo, Maria Rosa, Hoang, Thanh, Warnock, Alicia, Allen, Larry, Tang, Wilson, Chen, Horng H., and Cox, John M.

Published
2019
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13. Health-Related Quality of Life in Older Patients With Heart Failure From Before to Early After Advanced Surgical Therapies: Findings From the SUSTAIN-IT Study

Author

Grady, Kathleen L., primary, Kao, Andrew, additional, Spertus, John A., additional, Hsich, Eileen, additional, Dew, Mary Amanda, additional, Pham, Duc-Thinh, additional, Hartupee, Justin, additional, Petty, Michael, additional, Cotts, William, additional, Pamboukian, Salpy V., additional, Pagani, Francis D., additional, Lampert, Brent, additional, Johnson, Maryl, additional, Murray, Margaret, additional, Takeda, Koji, additional, Yuzefpolskaya, Melana, additional, Silvestry, Scott, additional, Kirklin, James K., additional, Andrei, Adin-Cristian, additional, Elenbaas, Christian, additional, Baldridge, Abigail, additional, and Yancy, Clyde, additional

Published
2022
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18. Health‐Related Quality of Life in Older Patients With Advanced Heart Failure: Findings From the SUSTAIN‐IT Study

Author

Grady, Kathleen L., primary, Andrei, Adin‐Cristian, additional, Elenbaas, Christian, additional, Warzecha, Anna, additional, Baldridge, Abigail, additional, Kao, Andrew, additional, Spertus, John A., additional, Pham, Duc‐Thinh, additional, Dew, Mary Amanda, additional, Hsich, Eileen, additional, Cotts, William, additional, Hartupee, Justin, additional, Pamboukian, Salpy V., additional, Pagani, Francis D., additional, Petty, Michael, additional, Lampert, Brent, additional, Johnson, Maryl, additional, Murray, Margaret, additional, Takeda, Koji, additional, Yuzefpolskaya, Melana, additional, Silvestry, Scott, additional, Kirklin, James K., additional, and Yancy, Clyde, additional

Published
2022
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19. Abstract 9364: Caregiver Anxiety Significantly Reduced from Baseline to 24 Months After Surgery: Findings from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Circulatory Support ( Sustain-it) Study

Author

Petty, Michael, primary, Wu, Tingqing, additional, Andrei, Adin-cristian, additional, Baldridge, Abigail S, additional, Warzecha, Anna, additional, Kao, Andrew, additional, Spertus, John, additional, Hsich, Eileen M, additional, Dew, Mary Amanda, additional, Pham, Duc Thinh, additional, Hartupee, Justin, additional, Cotts, William, additional, Pamboukian, Salpy, additional, Pagani, Francis D, additional, Lampert, Brent, additional, Johnson, Maryl R, additional, Murray, Margaret A, additional, Takeda, Koji, additional, yuzefpolskaya, melana, additional, Silvestry, Scott, additional, Kirklin, James K, additional, Yancy, Clyde, additional, and Grady, Kathleen L, additional

Published
2021
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20. Abstract 11455: Does Caregiver Burden Change from Before to 24 Months After Surgery: Findings from the Sustaining Quality of Life of the Aged: Heart Transplant or Mechanical Support ( Sustain-it ) Study

Author

Wu, Tingqing, primary, Andrei, Adin-cristian, additional, Baldridge, Abigail S, additional, Warzecha, Anna, additional, Petty, Michael, additional, Kao, Andrew, additional, Spertus, John, additional, hsich, eileen, additional, Dew, Mary Amanda, additional, Pham, Duc, additional, LaRue, Shane, additional, Cotts, William, additional, Pamboukian, Salpy, additional, Pagani, Francis D, additional, Lampert, Brent, additional, Johnson, Maryl R, additional, Hartupee, Justin, additional, Takeda, Koji, additional, Yuzefpolskaya, Melana, additional, Silvestry, Scott, additional, Kirklin, James, additional, Yancy, Clyde, additional, and Grady, Kathleen L, additional

Published
2021
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25. Dapagliflozin effects on lung fluid volumes in patients with heart failure and reduced ejection fraction: Results from the DEFINE‐HF trial

Author

Nassif, Michael E., primary, Windsor, Sheryl L., additional, Tang, Fengming, additional, Husain, Mansoor, additional, Inzucchi, Silvio E., additional, McGuire, Darren K., additional, Pitt, Bertram, additional, Scirica, Benjamin M., additional, Austin, Bethany, additional, Fong, Michael W., additional, LaRue, Shane J., additional, Umpierrez, Guillermo, additional, Hartupee, Justin, additional, Khariton, Yevgeniy, additional, Malik, Ali O., additional, Ogunniyi, Modele O., additional, Wenger, Nanette K., additional, and Kosiborod, Mikhail N., additional

Published
2021
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28. Change In Health-related Quality of Life from Before To 1 Year After Surgery: Findings from Sustain-it

Author

Grady, Kathleen L., primary, Andrei, Adin-Cristian, additional, Wu, Tingqing, additional, Warzecha, Anna, additional, Kao, Andrew, additional, Spertus, John, additional, Dew, Mary Amanda, additional, Sciortino, Christopher, additional, Thinh-Pham, Duc, additional, Hsich, Eileen, additional, Cotts, William, additional, Hartupee, Justin, additional, Petty, Michael, additional, Pamboukian, Salpy, additional, Pagani, Francis, additional, Lampert, Brent, additional, Johnson, Maryl, additional, Murray, Margaret, additional, Takeda, Koji, additional, Yuzefpolskaya, Melana, additional, Silvestry, Scott, additional, Kirklin, James, additional, Collum, S Craig, additional, and Yancy, Clyde, additional

Published
2020
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29. Association of bleeding with serotonergic antidepressants in patients receiving left ventricular assist device support.

Author

Robinson, Adam C., January, Spenser E., Botkin, Kent W., Vader, Justin M., Hartupee, Justin C., and Tellor Pennington, Bethany R.

Subjects
HEART assist devices, ANGIOTENSIN-receptor blockers, ANGIOTENSIN converting enzyme, HEMORRHAGE, GASTROINTESTINAL hemorrhage, CEREBRAL hemorrhage
Abstract

Study Objective: This study sought to determine whether SA use is associated with bleeding in patients receiving CF‐LVAD support. Design: A retrospective cohort analysis was conducted of all adult patients who received CF‐LVAD implantation at our institution. Setting: Barnes‐Jewish Hospital between July 1, 2009, and October 1, 2018. Patients: Patients at least 18 years of age who received a HVAD™ (HeartWare Corp.), HeartMate II™ (St. Jude Medical), or HeartMate 3™ (St. Jude Medical) CF‐LVAD and survived for at least 30 days postoperatively were included. Intervention: Patients who received SAs (n = 203) were compared to those who did not (n = 391) from 30 days to 18 months following implantation. The primary outcome was the incidence of first bleeding events including gastrointestinal bleed (GIB), epistaxis, or intracerebral hemorrhage (ICH). Measurements and Main Results: During follow‐up, 219 patients had bleeding events: 93 of 203 (45.8%) in the SA group versus 126 of 391 (32.2%) in the control group (p = 0.001). After adjustment for age, angiotensin‐converting enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) use, history of bleeding events, history of smoking, and CF‐LVAD type, SA use remained associated with bleeding (adjusted odds ratio: 1.75, 95% confidence interval: 1.22–2.51, p = 0.002). HeartMate 3™ patients experienced less bleeding than HeartMate II™ patients (adjusted odds ratio 0.46, 95% confidence interval: 0.23–0.90, p = 0.024). Conclusions: In this single‐center, retrospective cohort of patients supported with CF‐LVADs, SA use was associated with the incidence of first bleeding events, primarily driven by GIB. Further studies are needed to assess any differential risk of bleeding among SA agents and to assess the utility of altering antithrombotic strategies. [ABSTRACT FROM AUTHOR]

Published
2022
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37. Interleukin-17 regulates CXCL1 mRNA stability via an AUUUA/Tristetraprolin-independent sequence1

Author

Datta, Shyamasree, Novotny, Michael, Pavicic, Paul G., Zhao, Chenyang, Herjan, Tomasz, Hartupee, Justin, and Hamilton, Thomas

Subjects
Base Sequence, Chemokine CXCL1, RNA Stability, Interleukin-17, Molecular Sequence Data, RNA-Binding Proteins, Zinc Fingers, Article, Cell Line, Mice, Tristetraprolin, Mutagenesis, Site-Directed, Animals, Humans, RNA, Messenger, Transgenes, 3' Untranslated Regions, Cells, Cultured, HeLa Cells
Abstract

Interleukin (IL)-17 contributes to inflammatory response in part by promoting enhanced expression of chemokines such as CXCL1 by prolonging the half-life of this constitutively unstable mRNA. While IL-17 is a weak stimulus for transcription of the CXCL1 gene, it strongly potentiates message accumulation via stabilization when the mRNA is transcribed in cells stimulated with TNF. In myeloid cells, LPS-induced CXCL1 mRNA stabilization is dependent upon AUUUA-containing sequence motifs that are recognized by the RNA binding protein Tristetraprolin (TTP). Using deletion and site specific mutagenesis, we now report that IL-17-mediated stabilization of CXCL1 mRNA in non-myeloid cells depends upon a sequence that does not contain the AUUUA motif. Furthermore, a specific two nucleotide mutation within this region markedly abrogates sensitivity for IL-17-mediated stabilization. Consistent with this finding, the IL-17-sensitive sequence does not exhibit increased instability in the presence of TTP, and CXCL1 mRNA remains unstable and can be stabilized in response to treatment with IL-17 in embryo fibroblasts (MEFs) from mice in which the TTP gene has been deleted. While the RNA binding protein KSRP has been shown to participate in regulating the instability of human CXCL8 mRNA, RNAi-based reduction in KSRP does not impact the instability mediated by the IL-17-sensitive sequence motif. These findings suggest that IL-17-mediated chemokine mRNA stabilization in non-myeloid cells utilizes a mechanism that is distinct from that operating to control AU-rich mRNA stability in myeloid cells.

Published
2009

44. The adaptor Act1 is required for interleukin 17–dependent signaling associated with autoimmune and inflammatory disease

Author

Qian, Youcun, primary, Liu, Caini, additional, Hartupee, Justin, additional, Altuntas, Cengiz Zubeyir, additional, Gulen, Muhammet Fatih, additional, Jane-wit, Daniel, additional, Xiao, Jianhua, additional, Lu, Yi, additional, Giltiay, Natalia, additional, Liu, Jinbo, additional, Kordula, Tomasz, additional, Zhang, Qi-Wei, additional, Vallance, Bruce, additional, Swaidani, Shadi, additional, Aronica, Mark, additional, Tuohy, Vincent K, additional, Hamilton, Thomas, additional, and Li, Xiaoxia, additional

Published
2007
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46. Interleukin 1 α-induced NFκB Activation and Chemokine mRNA Stabilization Diverge at IRAK1.

Author

Hartupee, Justin, Xiaoxia Li, and Hamilton, Thomas

Subjects
*INTERLEUKIN-1, *CHEMOKINES, *MESSENGER RNA, *GENE expression, *GENETIC regulation, *GENETIC transcription
Abstract

Interleukin 1α (IL-1α) is capable of driving pro-inflammatory gene expression through both the initiation of transcription and by prolonging the half-life of short-lived mRNAs. Although the signaling events linking the IL-1 receptor to the activation of NFκB and the initiation of transcription have been well characterized, less is known about the signaling events linking to mRNA stabilization. As a model to study the control of mRNA stability we have used the mouse chemokine KC, expression of which requires both NFKB-driven transcription and stabilization of the constitutively unstable mRNA. We have evaluated the role of signaling adaptors known to play a role in IL-1α-driven NFαB activation in the generation of mRNA stability. Surprisingly, although TRAF6 is essential for NFκB activation, it is not required for IL-1α-induced mRNA stabilization. IRAK1, which is recognized to function upstream of TRAF6, is required for both mRNA stabilization and activation of NFB. Consistent with the previous findings, the TRAF6 interaction sites in IRAK1 are required for NFαB activation but do not play a role in mRNA stabilization. These findings indicate that signals from the IL-1 receptor segregate into at least two separate pathways at the level of IRAK1; one couples through TRAF6 to NFκB activation while a second utilizes a TRAF6-independent pathway that is responsible for mRNA stabilization. [ABSTRACT FROM AUTHOR]

Published
2008
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47. Cell type‐ and stimulus‐specific mechanisms for post‐transcriptional control of neutrophil chemokine gene expression

Author

Hamilton, Thomas, Li, Xiaoxia, Novotny, Michael, Pavicic, Paul G., Datta, Shyamasree, Zhao, Chenyang, Hartupee, Justin, and Sun, Dongxu

Abstract

Review on chemokine gene expression and its control by multiple post‐transcriptional mechanisms that exhibit differential cell type utilization and stimulus dependency. mRNAs encoding inflammatory chemokines that recruit neutrophils frequently exhibit short half‐lives that serve to limit their expression under inappropriate conditions but are often prolonged to ensure adequate levels during inflammatory response. Extracellular stimuli that modulate the stability of such mRNAs may be the same as the transcriptional activator, as is the case with TLR ligands, or may cooperate with independent transcriptional stimuli, as with IL‐17, which extends the half‐life of TNF‐induced transcripts. These different stimuli engage independent signaling pathways that target different instability mechanisms distinguished by dependence on different regulatory nucleotide sequence motifs within the 3′UTRs, which involve that action of different mRNA‐binding proteins. The selective use of these pathways by different stimuli and in distinct cell populations provides the potential for tailoring of chemokine expression patterns to meet specific needs in different pathophysiologic circumstances.

Published
2012
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48. Regulation of mRNA Stability in Chemokine Gene Expression

Author

Hartupee, Justin Curtis

Subjects
Immunology, Pathology, TRAF6, IL-17, MRNA, mRNA Stabilization, IRAK1, Act1, TNF
Abstract

Proper expression of pro-inflammatory genes, including ELR+ CXC chemokines, is achieved through regulation of transcription and post-transcriptional processes including mRNA decay. Modulation of transcription is an important means of achieving stimulus-induced expression and the mechanisms of this response have been well-characterized. mRNA stability is becoming increasingly recognized as a critical factor influencing expression of these genes. The mRNAs are constitutively unstable, but are stabilized in response to a variety of stimuli to allow robust expression.IL-17-induced gene expression has emerged as a critical factor driving inflammation in both host defense and autoimmunity. However, the molecular mechanisms by which IL-17 regulates expression are poorly understood. IL-17 alone has little effect on gene expression, but induces a synergistic response in combination with TNFα. We have determined that this observation is explained by the finding that IL-17 has relatively little effect on transcription, but rather works primarily through mRNA stabilization. It thus cooperates with TNFα, which drives transcription but is unable to prolong mRNA half-life, by providing a distinct requirement for gene expression. Although the adaptors Act1 and TRAF6 have both been previously reported to be essential for IL-17-induced responses, we find that only Act1 is involved in mRNA stabilization. Taken together our finds indicate the existence of a novel signaling pathway downstream of Act1 that is responsible for mRNA stabilization and plays a central role in IL-17-induced gene expression. The finding that IL-17-induced stabilization does not require TRAF6 raised questions regarding the role of this adaptor in IL-1α-induced mRNA stabilization. Although all IL-1α driven responses previously examined, including NF-κB and MAP kinase activation, require TRAF6, surprisingly we have found that TRAF6 is not required for IL-1α-induced mRNA stabilization. The signals leading to these earlier examined endpoints and mRNA stabilization diverge at IRAK1, the molecule immediately upstream of TRAF6 in the pathway. Collectively, these findings further highlight the importance of the regulation of mRNA stability in pro-inflammatory gene expression and provide understanding of the receptor proximal signaling events that allow IL-17 and IL-1α to link to this endpoint.

Published
2008

49. IL-17 regulates CXCL1 mRNA stability via an AUUUA/tristetraprolin-independent sequence.

Author

Datta S, Novotny M, Pavicic PG Jr, Zhao C, Herjan T, Hartupee J, and Hamilton T

Subjects
Animals, Base Sequence, Cell Line, Cells, Cultured, Chemokine CXCL1 physiology, HeLa Cells, Humans, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, RNA, Messenger genetics, RNA-Binding Proteins biosynthesis, RNA-Binding Proteins genetics, RNA-Binding Proteins physiology, Transgenes immunology, Tristetraprolin deficiency, Tristetraprolin physiology, Zinc Fingers genetics, Zinc Fingers immunology, 3' Untranslated Regions immunology, Chemokine CXCL1 genetics, Chemokine CXCL1 metabolism, Interleukin-17 physiology, RNA Stability immunology, RNA, Messenger metabolism, Tristetraprolin genetics, Tristetraprolin metabolism
Abstract

IL-17 contributes to inflammatory response in part by promoting enhanced expression of chemokines, such as CXCL1, by prolonging the t(1/2) of this constitutively unstable mRNA. Although IL-17 is a weak stimulus for transcription of the CXCL1 gene, it strongly potentiates message accumulation via stabilization when the mRNA is transcribed in cells stimulated with TNF. In myeloid cells, LPS-induced CXCL1 mRNA stabilization is dependent on AUUUA-containing sequence motifs that are recognized by the RNA binding protein tristetraprolin (TTP). Using deletion and site-specific mutagenesis, we report that IL-17-mediated stabilization of CXCL1 mRNA in nonmyeloid cells depends on a sequence that does not contain the AUUUA motif. Furthermore, a specific two-nucleotide mutation within this region markedly abrogates sensitivity for IL-17-mediated stabilization. Consistent with this finding, the IL-17-sensitive sequence does not exhibit increased instability in the presence of TTP, and CXCL1 mRNA remains unstable and can be stabilized in response to treatment with IL-17 in embryo fibroblasts from mice in which the TTP gene has been deleted. Whereas the RNA binding protein KSRP has been shown to participate in regulating the instability of human CXCL8 mRNA, inhibitory RNA-based reduction in KSRP does not effect the instability mediated by the IL-17-sensitive sequence motif. These findings suggest that IL-17-mediated chemokine mRNA stabilization in nonmyeloid cells uses a mechanism that is distinct from that operating to control AU-rich mRNA stability in myeloid cells.

Published
2010
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