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2018 ATS BEAR Cage Winning Proposal: Cell-Free DNA to Improve Lung Transplant Outcomes

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE (2019)

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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Volume 199, Issue 9, Pages 1058-1060

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AMER THORACIC SOC

DOI: 10.1164/rccm.201902-0458ED

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Telemedicine in lung transplant to improve patient-centered care: A systematic review

Marsa Gholamzadeh, Hamidreza Abtahi, Reza Safdari

Summary: This study investigates the usage of Telemedicine and telehealth in lung transplantation and finds that remote patient care plays a significant role in improving outcomes.

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The Aviary Transect-a practical welfare assessment tool to improve the management of cage-free laying hens

Guro Vasdal, Ruth C. Newberry, Inma Estevez, Kathe Kittelsen, Joanna Marchewka

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Lorry Becot, Nicolas Bedere, Thierry Burlot, Jenna Coton, Pascale Le Roy

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PLOS ONE (2021)

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Article Surgery

Comparison of donor-derived cell-free DNA between single versus double lung transplant recipients

Michael B. Keller, Rohan Meda, Sheng Fu, Kai Yu, Moon Kyoo Jang, Ananth Charya, Gerald J. Berry, Charles C. Marboe, Hyesik Kong, Helen Luikart, Ileana L. Ponor, Pali D. Shah, Kiran K. Khush, Steven D. Nathan, Sean Agbor-Enoh

Summary: This study compared plasma dd-cfDNA levels in single and double lung transplant recipients in stable and acute rejection states, finding lower levels in single lung transplant recipients. Adjusting for differences in lung mass eliminated this difference, emphasizing the importance of considering such differences in interpreting dd-cfDNA testing.

AMERICAN JOURNAL OF TRANSPLANTATION (2022)

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Article Respiratory System

Impact of antigen identification on transplant free survival in interstitial lung disease

Margaret Kypreos, Kiran Batra, Craig S. Glazer, Traci N. Adams

Summary: Antigen identification is important for patients with hypersensitivity pneumonitis, but may not have a significant impact on other interstitial lung diseases. Diagnosis with bronchoalveolar lavage and transbronchial biopsy prior to recommending antigen removal is recommended.

BMC PULMONARY MEDICINE (2023)

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Article Respiratory System

Application of plasma donor-derived cell free DNA for lung allograft rejection diagnosis in lung transplant recipients

Chunrong Ju, Xin Xu, Jianheng Zhang, Ao Chen, Qiaoyan Lian, Feng Liu, Haitao Liu, Yuhang Cai, Yanjun Zou, Yalan Yang, Yang Zhou, Jianxing He

Summary: This study investigated the application of donor-derived cell-free DNA (dd-cfDNA) levels in diagnosing acute rejection (AR) and chronic lung allograft dysfunction (CLAD) in lung transplantation recipients (LTRs). The results showed significant differences in dd-cfDNA levels among the four groups, with the highest level in the AR group, followed by the CLAD group, and the lowest level in the infection group. The AUC-ROC curve analysis determined the thresholds for AR and CLAD diagnosis as 1.17% and 0.89%, respectively.

BMC PULMONARY MEDICINE (2023)

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Article Medicine, General & Internal

Chronic Lung Allograft Dysfunction Is Associated with Increased Levels of Cell-Free Mitochondrial DNA in Bronchoalveolar Lavage Fluid of Lung Transplant Recipients

Emmanuel Schneck, Ingolf Askevold, Ramona Rath, Andreas Hecker, Martin Reichert, Stefan Guth, Christian Koch, Michael Sander, Werner Seeger, Konstantin Mayer, Winfried Padberg, Natascha Sommer, Stefan Kuhnert, Matthias Hecker

Summary: This study found that the concentration of mtDNA in bronchoalveolar lavage can potentially serve as a predictor for the early detection and differentiation of different stages of CLAD, independent of the underlying pathology.

JOURNAL OF CLINICAL MEDICINE (2022)

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Article Cardiac & Cardiovascular Systems

Donor-derived cell-free DNA accurately detects acute rejection in lung transplant patients, a multicenter cohort study

Moon Kyoo Jang, Ilker Tunc, Gerald J. Berry, Charles Marboe, Hyesik Kong, Michael B. Keller, Pali D. Shah, Irina Timofte, Anne W. Brown, Ileana L. Ponor, Cedric Mutebi, Mary C. Philogene, Kai Yu, Aldo Iacono, Jonathan B. Orens, Steven D. Nathan, Sean Agbor-Enoh

Summary: This study demonstrates that %ddcfDNA reliably detects acute rejection and other clinical complications potentially missed by histopathology, lending support to its use as a non-invasive marker of allograft injury.

JOURNAL OF HEART AND LUNG TRANSPLANTATION (2021)

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Article Hematology

Checkpoint inhibitor-based salvage regimens prior to autologous stem cell transplant improve event-free survival in relapsed/refractory classic Hodgkin lymphoma

Sanjal H. Desai, Michael A. Spinner, Kevin David, Veronika Bachanova, Gaurav Goyal, Brad Kahl, Kathleen Dorritie, Jacques Azzi, Vaishalee P. Kenkre, Sally Arai, Cheryl Chang, Brendon Fusco, Nuttavut Sumransub, Haris Hatic, Raya Saba, Uroosa Ibrahim, Elyse Harris, Harsh Shah, Jacob Murphy, Stephen Ansell, Deepa Jagadish, Victor Orellana-noia, Catherine Diefenbach, Siddharth Iyenger, K. C. Rappazzo, Rahul Mishra, Yun Choi, Grzegorz S. Nowakowski, Ranjana H. Advani, Ivana N. Micallef

Summary: This multicenter retrospective study found that salvage therapies with checkpoint inhibitor (CPI)-based regimens had superior event-free survival (EFS) and progression-free survival (PFS) compared to conventional chemotherapy and other salvage regimens, supporting the use of CPI-based regimens in relapsed/refractory transplant-eligible classic Hodgkin lymphoma (R/R cHL) in the pre-autologous stem cell transplant (ASCT) setting.

AMERICAN JOURNAL OF HEMATOLOGY (2023)

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Article Surgery

CTOTC-08: A multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients

Stuart C. Sweet, Brian Armstrong, Joshua Blatter, Hyunsook Chin, Carol Conrad, Samuel Goldfarb, Don Hayes, Peter S. Heeger, Victoria Lyou, Ernestina Melicoff-Portillo, Thalachallour Mohanakumar, Jonah Odim, Ranjithkumar Ravichandran, Marc Schecter, Gregory A. Storch, Gary Visner, Nikki M. Williams, Lara Danziger-Isakov

Summary: The study showed that rituximab induction may prevent early DSA development in pediatric lung transplant recipients without adverse effects, but did not significantly differ from the placebo group in terms of the primary endpoint and incidence of adverse events.

AMERICAN JOURNAL OF TRANSPLANTATION (2022)

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Article Biochemistry & Molecular Biology

Analysis and Fine Specificity of the HCMV-Specific Cell-Free and Cell-Associated Antibody-Dependent Cellular Phagocytosis (ADCP) Responses in Lung Transplant Recipients

Simone Eberhard, Hannes Vietzen, Irene Goerzer, Peter Jaksch, Elisabeth Puchhammer-Stoeckl

Summary: The study found that a strong HCMV-specific ADCP response is elicited in transplant recipients, which may contribute to protection from high-level viremia in primary HCMV infection, especially after receiving a lung transplant from an HCMV-positive donor.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Transplantation

Lung Transplant Candidates With Pretransplant Gastroesophageal Reflux and Antibodies to Lung Self-antigens Have Shorter CLAD-free Survival After Transplant

Deepika Razia, Sumeet K. Mittal, Sandhya Bansal, Ranjithkumar Ravichandran, Michael A. Smith, Rajat Walia, Ross M. Bremner, Thalachallour Mohanakumar, Sofya Tokman

Summary: This study found that pre-lung transplant gastroesophageal reflux (GER) or circulating antibodies against lung self-antigens (SAbs) may increase the risk of chronic lung allograft dysfunction (CLAD) in recipients. The association suggests that GER may cause an immune response to lung-associated self-antigens, leading to ongoing lung injury.

TRANSPLANTATION DIRECT (2022)

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Proceedings Paper Computer Science, Artificial Intelligence

Predicting left/right lung volumes, thoracic cavity volume, and heart volume from subject demographics to improve lung transplant

Lucas Pu, Joseph K. Leader, Alaa Ali, Zihan Geng, David Wilson

Summary: This study used chest CT scans and basic demographics to predict lung, heart, and thoracic cavity volumes. U-Net was used to segment the organs, and eight machine learning models were developed for volume prediction. The results showed that the MLP model performed best for thoracic cavity volume, right lung volume, and left lung volume, while the XGBoost model performed best for total lung volume and heart volume.

MEDICAL IMAGING 2023 (2023)

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Article Medical Laboratory Technology

Biological Variation of Donor-Derived Cell-Free DNA in Stable Lung Transplant Recipients

Michael Keller, Cedric Mutebi, Pali Shah, Deborah Levine, Shambhu Aryal, Aldo Iacono, Irina Timofte, Joby Mathew, Anu Varghese, Cassandra Giner, Sean Agbor-Enoh

Summary: This study establishes the biological variation and reference change values of dd-cfDNA in stable lung transplant recipients. The results show that 96% of dd-cfDNA levels were within the normal biological variation range, indicating no abnormal results.

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Radiomic-signature changes after early treatment improve the prediction of progression-free survival in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung cancer

Donghui Hou, Xiaomin Zheng, Wei Song, Xiaoqing Liu, Sicong Wang, Lina Zhou, Xiuli Tao, Lv Lv, Qi Sun, Yujing Jin, Zewei Zhang, Lieming Ding, Ning Wu, Shijun Zhao

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Article Cardiac & Cardiovascular Systems

Applying rigor and reproducibility standards to assay donor-derived cell-free DNA as a non-invasive method for detection of acute rejection and graft injury after heart transplantation

Sean Agbor-Enoh, Ilker Tunc, Iwijn De Vlaminck, Ulgen Fideli, Andrew Davis, Karen Cuttin, Kenneth Bhatti, Argit Marishta, Michael A. Solomon, Annette Jackson, Grace Graninger, Bonnie Harper, Helen Luikart, Jennifer Wylie, Xujing Wang, Gerald Berry, Charles Marboe, Kiran Khush, Jun Zhu, Hannah Valantine

JOURNAL OF HEART AND LUNG TRANSPLANTATION (2017)

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Article Cardiac & Cardiovascular Systems

Circulating cell-free DNA as a biomarker of tissue injury: Assessment in a cardiac xenotransplantation model

Sean Agbor-Enoh, Joshua L. Chan, Avneesh Singh, Ilker Tunc, Sasha Gorham, Jun Zhu, Mehdi Pirooznia, Philip C. Corcoran, Marvin L. Thomas, Billeta G. T. Lewis, Moon Kyoo Jang, David L. Ayares, Keith A. Horvath, Muhammad M. Mohiuddin, Hannah Valantine

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Single-stranded DNA library preparation uncovers the origin and diversity of ultrashort cell-free DNA in plasma

Philip Burnham, Min Seong Kim, Sean Agbor-Enoh, Helen Luikart, Hannah A. Valantine, Kiran K. Khush, Iwijn De Vlaminck

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Environment, Epigenetics, and Differential Responses to Beryllium Exposure: Are We There Yet?

Samuel Brusca, Sean Agbor-Enoh

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De novo mutations in mitochondrial DNA of iPSCs produce immunogenic neoepitopes in mice and humans

Tobias Deuse, Xiaomeng Hu, Sean Agbor-Enoh, Martina Koch, Matthew H. Spitzer, Alessia Gravina, Malik Alawi, Argit Marishta, Bjoern Peters, Zeynep Kosaloglu-Yalcin, Yanqin Yang, Raja Rajalingam, Dong Wang, Bjoern Nashan, Rainer Kiefmann, Hermann Reichenspurner, Hannah Valantine, Irving L. Weissman, Sonja Schrepfer

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Article Cardiac & Cardiovascular Systems

Cell-Free DNA to Detect Heart Allograft Acute Rejection

Sean Agbor-Enoh, Palak Shah, Ilker Tunc, Steven Hsu, Stuart Russell, Erika Feller, Keyur Shah, Maria E. Rodrigo, Samer S. Najjar, Hyesik Kong, Mehdi Pirooznia, Ulgen Fideli, Alfiya Bikineyeva, Argit Marishta, Kenneth Bhatti, Yanqin Yang, Cedric Mutebi, Kai Yu, Moon Kyoo Jang, Charles Marboe, Gerald J. Berry, Hannah A. Valantine

Summary: This study validated the use of %ddcfDNA as a sensitive blood biomarker for detecting acute rejection in cardiac transplant recipients. It showed excellent performance characteristics in early detection and could potentially reduce the need for invasive endomyocardial biopsies.

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Letter Cardiac & Cardiovascular Systems

Response by Shah et al to Letter Regarding Article, Cell-Free DNA to Detect Heart Allograft Acute Rejection

Palak Shah, Sean Agbor-Enoh, Ilker Tunc, Steven Hsu, Stuart Russell, Erika Feller, Keyur Shah, Maria E. Rodrigo, Samer S. Najjar, Hyesik Kong, Mehdi Pirooznia, Ulgen Fideli, Alfiya Bikineyeva, Argit Marishta, Kenneth Bhatti, Yanqin Yang, Cedric Mutebi, Kai Yu, Moon Kyoo Jang, Charles Marboe, Gerald J. Berry, Hannah A. Valantine

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Molecular Approaches to Transplant Monitoring; Is the Horizon Here?

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The effect of the cystic fibrosis care center on outcomes after lung transplantation for cystic fibrosis

Errol L. Bush, Aravind Krishnan, Alexis P. Chidi, Eric Nolley, Sean Agbor-Enoh, Natalie E. West, Erin Tallarico, Jonathan B. Orens, Jinny Ha, Pali D. Shah, Kathleen J. Ramos, Dorry Segev, Allan Massie, Robert SD. Higgins, Christian A. Merlo

Summary: This study evaluated outcomes in cystic fibrosis patients who underwent lung transplant at a transplant center with an accredited Cystic Fibrosis Care Center. The results showed that patients who underwent lung transplant at a hospital with an accredited CFCC had higher graft survival and a lower need for re-transplantation compared to those at non-accredited CFCC hospitals.

JOURNAL OF HEART AND LUNG TRANSPLANTATION (2022)

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Article Cardiac & Cardiovascular Systems

Circulating microRNAs in cellular and antibody- mediated heart transplant rejection

Palak Shah, Sean Agbor-Enoh, Pramita Bagchi, Christopher R. deFilippi, Angela Mercado, Gouqing Diao, Dave J. P. Morales, Keyur B. Shah, Samer S. Najjar, Erika Feller, Steven Hsu, Maria E. Rodrigo, Sabra C. Lewsey, Moon Kyoo Jang, Charles Marboe, Gerald J. Berry, Kiran K. Khush, Hannah A. Valantine, GRAfT Investigators

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Selection and Interpretation of Molecular Diagnostics in Heart Transplantation

Jason F. Goldberg, Lauren K. Truby, Sean Agbor-Enoh, Annette M. Jackson, Christopher R. deFilippi, Kiran K. Khush, Palak Shah

Summary: The number of heart transplants performed annually in the United States and worldwide continues to increase, but there has been little change in graft longevity and patient survival over the past 2 decades. The use of circulating biomarkers and molecular diagnostics has shown predictive value in rejection monitoring and diagnosing posttransplant complications. The understanding of immunogenetics has enhanced the knowledge of antibody-mediated rejection and the evaluation of donor human leukocyte antigens.

CIRCULATION (2023)

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Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation

Moon Kyoo Jang, Tovah E. Markowitz, Temesgen E. Andargie, Zainab Apalara, Skyler Kuhn, Sean Agbor-Enoh

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LIFE SCIENCE ALLIANCE (2023)

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Article Biochemistry & Molecular Biology

The NIH Lipo-COVID Study: A Pilot NMR Investigation of Lipoprotein Subfractions and Other Metabolites in Patients with Severe COVID-19

Rami A. Ballout, Hyesik Kong, Maureen Sampson, James D. Otvos, Andrea L. Cox, Sean Agbor-Enoh, Alan T. Remaley

Summary: There is a complex relationship between plasma lipoproteins and inflammation, especially in the context of diseases like atherosclerosis and respiratory viral infections. Severe COVID-19 patients exhibit altered plasma lipoprotein levels, including reduced HDL particles and increased triglyceride-rich lipoprotein particles, along with elevated levels of GlycA, branched-chain amino acids, and beta-hydroxybutyrate. Additionally, elevated levels of lipoproteins X and Z, markers of hepatic dysfunction, were detected in most participants, indicating a potential novel finding in this study.

BIOMEDICINES (2021)

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2018 ATS BEAR Cage Winning Proposal: Cell-Free DNA to Improve Lung Transplant Outcomes

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