tbuckley/cabot-search huggingface dataset:
SURG-02. NEUROSURGICAL RESECTION FOR LOCALLY RECURRENT BRAIN METASTASIS
Authors: Alexander Hulsbergen, Abdullah Abunimer, Fidelia Ida, Vasileios Kavouridis, Logan Cho, Ishaan Tewarie, Rania Mekary, Philippe Schucht, John Phillips, Joost Verhoeff, Marike Broekman, Timothy Smith
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In patients with locally recurrent brain metastases (LRBMs), the role of (repeat) craniotomy is controversial. This study aimed to analyze long-term oncological outcomes in this heterogeneous population. METHODS Craniotomies for LRBM were identified from a tertiary neuro-oncological institution. First, we assessed overall survival (OS) and intracranial control (ICC) stratified by molecular profile, prognostic indices, and multimodality treatment. Second, we compared LRBMs to propensity score-matched patients who underwent craniotomy for newly diagnosed brain metastases (NDBM). RESULTS Across 180 patients, median survival after LRBM resection was 13.8 months and varied by molecular profile, with &amp;gt;24 months survival in ALK/EGFR+ lung adenocarcinoma and HER2+ breast cancer. Furthermore, 102 patients (56.7%) experienced intracranial recurrence; median time to recurrence was 5.6 months. Compared to NDBMs (n = 898), LRBM patients were younger, more likely to harbor a targetable mutation and less likely to receive adjuvant radiation (p &amp;lt; 0.05). After 1:3 propensity matching stratified by molecular profile, LRBM patients generally experienced shorter OS (hazard ratio 1.67 and 1.36 for patients with or without a mutation, p &amp;lt; 0.05) but similar ICC (hazard ratio 1.11 in both groups, p &amp;gt; 0.20) compared to NDBM patients with similar baseline. Results across specific molecular subgroups suggested comparable effect directions of varying sizes. CONCLUSIONS In our data, patients with LRBMs undergoing craniotomy comprised a subgroup of brain metastasis patients with relatively favorable clinical characteristics and good survival outcomes. Recurrent status predicted shorter OS but did not impact ICC. Craniotomy could be considered in selected, prognostically favorable patients.
Human Placental CD34 +-Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 (CYNK-101) in Combination with Daratumumab for Immunotherapy Against CD38 Expressing Hematological Malignancies
Authors: Irene Raitman, Joseph Gleason, Salvatore Rotondo, Shuyang He, Valentina Rousseva, Xuan Guo, Hemlata Rana, William van der Touw, Qian Ye, Lin Kang, Robert Hariri, Xiaokui Zhang
Journal: Blood (2021)
Abstract 9840: National Trends in Statin Use for Secondary Prevention in the Adult Cardio-Oncology Population from 2006 to 2017
Authors: Evaline Cheng, Eric H Yang, Boback Ziaeian
Journal: Circulation (2021)

Introduction: Adults with a history of cancer may have increased risk of atherosclerotic cardiovascular disease (ASCVD) from cancer therapies and shared modifiable risk factors. While cancer history is associated with disparities in other areas of cardiology care, recent trends of secondary cardiovascular prevention in the cardio-oncology population is understudied. We examined trends in statin use for secondary prevention of ASCVD in the U.S. adult population. Hypothesis: We hypothesized that cancer history is associated with decreased statin use, and this trend persists over time. Methods: This retrospective longitudinal study included adults over age 21 with ASCVD, defined as a history of coronary artery disease (CAD) or stroke. Demographics, medical conditions, and prescribed medications between January 2006 and December 2017 were obtained from the Medical Expenditure Panel Survey database. Multivariable logistic regressions examined associations between cancer history and statin use, adjusting for age, sex, calendar year, socioeconomic variables, and comorbidities. Results: Among 26,813 adults with ASCVD, 4040 participants (15.1%) also had a history of cancer, defined as the cardio-oncology group. The cardio-oncology group was older on average compared to adults with only ASCVD (mean [SE], 70.9 [0.4] years vs. 65.1 [0.2] years; P &lt; 0.001). More adults in the cardio-oncology group also had a history of diabetes (33.9% vs. 30.6%, P = 0.01) or dyslipidemia (78.2% vs. 73.0%, P &lt; 0.001) compared to those with only ASCVD. Between 2006-2007 and 2016-2017, age-adjusted rates of statin use decreased from 35.7% to 32.6% in the ASCVD only group. Across the cardio-oncology group, age-adjusted rates of statin use also decreased from 43.4% to 35.8% during this period. In multivariable adjusted analysis, cancer history was associated with decreased odds of statin use across the 12-year period (OR 0.86; 95% CI 0.76-0.98). Conclusions: Adults with a history of ASCVD and cancer were significantly less likely to use statins for secondary prevention despite higher prevalences of diabetes and dyslipidemia. This treatment gap persisted across the 12-year period, identifying a need for more cardiovascular preventive care in the cardio-oncology population.
Abstract 9054: Cell-Specific Regulation of the GATA-4/6 Transcription Factors by the Metabolic Enzyme PKM2 Provides Insight into a Biologic Function Essential for Cardiac Health and Survival
Authors: Maria Areli Lorenzana Carrillo, Keshav Gopal, Nikole J Byrne, Bruno Saleme, Subhash K Das, Saymon Tejay, Yongneng Zhang, Alois S Haromy, Farah Eaton, Jason R Dyck, Evangelos D Michelakis, Gopinath Sutendra
Journal: Circulation (2021)

Background: Pyruvate Kinase M2 (PKM2) is a glycolytic enzyme that can translocate to the nucleus and regulate different transcription factors (TF). Although its function has been studied extensively in cancer, its biologic role in the heart, and specifically terminally differentiated adult cardiomyocytes (CM), remains elusive. Hypothesis: Because PKM1 is the more abundant isoform in CM, we speculated that PKM2 would not have a genetically redundant role to PKM1 and may instead be critical in regulating CM-specific TF. Methods: Transverse aortic constriction (TAC) banding model was used to assess the levels and modifications of PKM2 during heart failure (HF). CM-specific PKM2-deficient mice were generated to evaluate the biological role of PKM2 in adult CM. Unbiased RNA sequencing was utilized to assess novel PKM2-induced signaling pathways in adult CM. Induced pluripotent stem cells (iPSCs) were used to translate mechanistic findings to mature human CM. Results: PKM2 levels were lower, but serine-37 phosphorylated PKM2 ( S37 P-PKM2) was higher in terminally differentiated tissues. Cell-specific analysis showed S37 P-PKM2 was preferentially localized in the nucleus of CM, compared to cardiac fibroblasts (CF) (where PKM2 was mainly cytoplasmic). During TAC-induced HF, PKM2 levels increased in CF but correspondingly decreased in CM, in comparison to sham controls. CM-specific PKM2-deficient mice developed age-dependent cardiac dysfunction with decreased survival, compared to their control littermates. Unbiased RNA sequencing revealed a decrease in cardiac energetic, stress response, angiogenesis, repair and regeneration, and survival pathways from PKM2-deficient CM. In keeping, PKM2-deficient hearts had decreased levels of the cardiomyocyte-specific TF GATA4 and GATA6, compared to control hearts. Finally, the E3 ubiquitin-ligase TRIM35, which was induced during TAC-induced heart failure, ubiquitinated and degraded PKM2, along with GATA4 and GATA6 in primary adult mouse or human iPSC-derived CM. Conclusions: This study shows a new and previously unrecognized role for PKM2 in the regulation of cardiomyocyte-specific transcription factors and identifies a novel therapeutic target (TRIM35) in heart failure.
Author Correction: Experimental and real-world evidence supporting the computational repurposing of bumetanide for APOE4-related Alzheimer’s disease
Authors: Alice Taubes, Phil Nova, Kelly A. Zalocusky, Idit Kosti, Mesude Bicak, Misha Y. Zilberter, Yanxia Hao, Seo Yeon Yoon, Tomiko Oskotsky, Silvia Pineda, Bin Chen, Emily A. Aery Jones, Krishna Choudhary, Brian Grone, Maureen E. Balestra, Fayzan Chaudhry, Ishan Paranjpe, Jessica De Freitas, Nicole Koutsodendris, Nuo Chen, Celine Wang, William Chang, Alice An, Benjamin S. Glicksberg, Marina Sirota, Yadong Huang
Journal: Nature Aging (2021)
Efficacy and Safety of Sequential Different B Cell Antigen-Targeted CAR T-Cell Therapy for Pediatric Refractory/Relapsed Burkitt Lymphoma with Secondary Central Nervous System Involvement
Authors: Ying Liu, Biping Deng, Bo Hu, Wenqun Zhang, Qing Zhu, Yang Liu, Shan Wang, Pei Zhang, Junhan Yang, Qinlong Zheng, Xinjian Yu, Zifen Gao, Chunju Zhou, Wei Han, Alex Hong Chang, Yonghong Zhang
Journal: Blood (2021)
PK and PD Assessment of BET Inhibitor Pelabresib (CPI-0610) in Patients with Relapsed or Refractory Lymphoma: Findings from a Phase 1 Study
Authors: Kristie A. Blum, Jeffrey G. Supko, Michael Maris, Ian W. Flinn, Andre H. Goy, Anas Younes, Suresh Bobba, Adrian Senderowicz, Sergey Efuni, Ronda Rippley, Jeremy S. Abramson
Journal: Blood (2021)
A Pilot Phase I Trial of IL-21 Expanded Ideal-Donor Natural Killer (NK) Cells in Combination with Mogamulizumab in Patients with Cutaneous T-Cell Lymphomas (CTCL) or Adult T-Cell Leukemia/Lymphomas (ATLL)
Authors: Basem M. William, John C. Reneau, Amanda Campbell, Anna Vilgelm, Michelle Watts, Lynn O'Donnell, Ying Huang, Catherine Chung, Marcos J.G. de Lima, Steven Devine, Sumithira Vasu, Dean Anthony Lee
Journal: Blood (2021)
Relationship between Endogenous, Transgene FVIII Expression and Bleeding Events Following Valoctocogene Roxaparvovec Gene Transfer for Severe Hemophilia A: A Post-Hoc Analysis of the GENEr8-1 Phase 3 Trial
Authors: Steven W Pipe, Margareth C Ozelo, Gili Kenet, Mark T Reding, Jane Mason, Andrew D Leavitt, Bella Madan, Michael Laffan, Doris V. Quon, Annette von Drygalski, Sheng-Chieh Chou, Susan Shapiro, Amy L Dunn, Michael Wang, Nigel S Key, Radoslaw Kaczmarek, Emily Symington, Adebayo Lawal, Reena Mahajan, Konstantia-Maria Chavele, Divya B Reddy, Hua Yu, Wing Yen Wong, Tara M Robinson, Benjamin Kim
Journal: Blood (2021)
Gilteritinib for Relapsed Acute Myeloid Leukaemia with FLT3 Mutation during the COVID-19 Pandemic: Real World Experience from the UK National Health Service
Authors: Jad Othman, Usman Afzal, Ruebina Amofa, Michael J Austin, Alex Bashford, Edward Belsham, Jennifer Byrne, Thomas Coats, Raymond Dang, Mike Dennis, Saniya Dhawan, Johnathon Elliot, Sebastian Francis, Paolo Gallipoli, Katherine Hodgson, Charlotte Kallmeyer, Manish Jain, Vana Katsomitrou, Anjum Khan, Asim Khwaja, Seye Kolade, Pramila Krishnamurthy, Annie Latif, John Laurie, Michael Lim, (Justin) Ching Ting Loke, Cara Manson, Scott R. Marshall, Behnaz Mobashwera, Sreetharan Munisamy, Duncan Murray, Vidhya Murthy, Renuka Palanicawandar, Jamie Saunders, Matthew Smith, Katherine Smith, Alex Sternberg, David Taussig, Tom Taylor, Sylvie D Freeman, Charles Craddock, Richard Dillon
Journal: Blood (2021)
281 Measuring immune checkpoint inhibitor efficacy using primary patient-derived 3D spheroids
Authors: Kathryn Appleton, Katy Lassahn, Ashley Elrod, Tessa DesRochers
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Cancerous cells can utilize immune checkpoints to escape T-cell-mediated cytotoxicity. Agents that target PD-1, PD-L1 and CTLA4 are collectively deemed immune checkpoint inhibitors (ICIs), and many have been approved for treatment of non-small cell lung cancer (NSCLC) and melanoma. Unfortunately, many patients do not respond to these therapies and often experience disease progression. Immunohistochemistry assays to predict response to ICIs have been inconsistent in their readouts and often patients with low expression levels respond to ICIs. Understanding the determinants of ICI response in individual patients is critical for improving the clinical success of this drug class. Using patient-derived spheroids from NSCLC and melanoma primary tissue, we developed a multi-plexed assay for detecting ICI efficacy. Methods Nine NSCLC and 11 melanoma primary tumor samples were dissociated to single cells, classified for immune checkpoint expression and cell content by flow cytometry, and seeded for spheroid formation. Spheroids were treated with pembrolizumab, nivolumab, atezolizumab, ipilimumab or durvalumab across a range of concentrations and monitored for cytotoxicity at 24-hours and viability at 72-hours by multiplexing CellTox™ Green Cytotoxicity Assay and CellTiter-Glo® 3D Cell Viability Assay. IFNγ and granzyme B secretion was assessed using Luminex technology. ICI response was evaluated by determining the concentration-response relationship for all three read-outs. Results Increased IFNγ and granzyme B were detected for every ICI in one or more patient samples. ICI-induced IFNγ secretion inversely correlated with PD-1+ immune cells. Durvalumab was significantly more cytotoxic for both NSCLC and melanoma spheroids compared to the other ICIs and significantly reduced spheroid viability with mean spheroid survival decreasing to 19.5% for NSCLC and 58.2% for melanoma. We evaluated if there was an association between durvalumab response and cell composition and found that percent spheroid survival significantly correlated with CD8+ T-cells for both NSCLC (r=-0.7920, p=0.0191) and melanoma (r=-0.6918, p=0.0390). Furthermore, CD8+ T-cells correlated with durvalumab-induced granzyme B secretion for NSCLC (r=-0.7645, p=0.0271) and melanoma (r=-0.7419, p=0.0221). Conclusions In this study we show ICI-specific increases in immune-related analytes in a concentration-dependent manner for NSCLC and melanoma patient-derived spheroids. We detected spheroid cytotoxicity following short term ICI treatment which closely mirrored decreased spheroid viability at a later timepoint. Finally, we can decipher response mechanisms as exemplified by durvalumab-induced granzyme B secretion correlating with the presence of CD8+ T-cells which results in reduced spheroid viability for both tested cancer indications.
Antitumor Activity of Dual BCL-2/BCL-Xl Inhibitor Pelcitoclax (APG-1252) in Natural Killer/T-Cell Lymphoma (NK/TCL)
Authors: Guangfeng Wang, Eric Liang, Ping Ming, Li Rui, Chunyang Tang, Jing LV, Yangfeng Ge, Fei Zhang, Lvcheng Wang, Jingjin Shang, Dajun Yang, Yifan Zhai
Journal: Blood (2021)
Elotuzumab in Combination with Lenalidomide, Bortezomib, Dexamethasone and Autologous Transplantation for Newly-Diagnosed Multiple Myeloma: Results from the Randomized Phase III GMMG-HD6 Trial
Authors: Hartmut Goldschmidt, Elias K Mai, Uta Bertsch, Britta Besemer, Mathias Haenel, Kaya Miah, Roland Fenk, Jana Schlenzka, Markus Munder, Jan Dürig, Igor Wolfgang Blau, Stefanie Huhn, Dirk Hose, Anna Jauch, Christina Kunz, Andreas Neubauer, Christof Scheid, Roland Schroers, Ivana v. Metzler, Aneta Schieferdecker, Joerg Thomalla, Peter Reimer, Rolf Mahlberg, Ullrich Graeven, Stephan Kremers, Uwe M. Martens, Christian Kunz, Manfred Hensel, Andrea Seidel-Glaetzer, Katja Weisel, Marc-Steffen Raab, Hans Salwender
Journal: Blood (2021)
SARS-CoV-2 Spike-Specific T-Cell Responses in Patients With B-Cell Depletion Who Received Chimeric Antigen Receptor T-Cell Treatments
Authors: Kalpana Parvathaneni, Kyabeth Torres-Rodriguez, Wenzhao Meng, Wei-Ting Hwang, Noelle Frey, Ali Naji, Vijay G. Bhoj
Journal: JAMA Oncology (2021)

This cohort study examines the ability of patients receiving chimeric antigen receptor T-cell treatments to mount T-cell immunity in response to messenger RNA vaccines for severe acute respiratory syndrome coronavirus 2 despite substantial B-cell depletion.
Abstract 10046: Racial Disparity in Patients Undergoing Thoracic Endovascular Aortic Repair for Thoracic Aortic Aneurysms and Dissections
Authors: Derek R Serna-Gallegos, Edgar Aranda-Michel, James Brown, Sarah Yousef, Yisi Wang, forozan navid
Journal: Circulation (2021)

Introduction: Thoracic Endovascular Aortic Repair (TEVAR) has become the standard of care for treating complicated type B aortic dissection and descending thoracic aortic aneurysms. There are no large datasets evaluating racial disparities in patients undergoing TEVAR. Hypothesis: There is no difference in outcomes between patients of different ethnicities and race undergoing TEVAR. Methods: We analyzed adult patients who underwent TEVAR for complicated type B aortic dissection or descending thoracic aortic aneurysm. International Classification of Diseases, Ninth Revision, were used to identify patients. We utilized the National Inpatient Sample database, from January 1, 2010 to December 31, 2017. Appropriate trend weights were used to generate national estimates. Primary outcome measure was in hospital mortality. Predictors of mortality were determined using hierarchical logistic regression and a mixed logistic model was used to account for hospital variations. Excluded patients were less than 18 years old. Results: The study population consisted of 25260 patients. There were 17197 (68.07%) white patients, 4959 (19.66%) black patients, 1462 (5.74%) Hispanic patients and 1642 (6.51%) patients of various other ethnicities and races. Although the Elixhauser comorbidity index was not significantly different between groups, white patients were older, underwent more elective repairs, had lower baseline rates of diabetes mellitus, hypertension and chronic kidney disease. There was no significant difference when comparing in hospital mortality between white (reference group), black (OR 0.86, p=0.46), Hispanic (OR 1.54, p=0.13) or other groups (OR 0.78, p=0.45). Non elective TEVAR (OR 2.23, p&lt;0.001), presence of other cardiac conditions (OR 2.68, p&lt;0.001), and preoperative diagnosis of cerebral vascular disease (OR 2.39, p&lt;0.001), peripheral vascular disease (OR 1.62, p=0.00) and chronic kidney disease (OR 1.45, p=0.04) were significant predictors of in hospital mortality. Conclusions: While patients of color were older and had more peripheral vascular disease and chronic obstructive pulmonary disease racial differences did not predict in hospital mortality.
Axicabtagene Ciloleucel in Relapsed or Refractory Large B-Cell Lymphoma Patients in Complete Metabolic Response at Time of Infusion
Authors: Sushanth Gouni, Jason R. Westin, Haleigh Mistry, Raphael Eric Steiner, Jinsu James, Simrit Parmar, Mansoor Noorani, Nathan H. Fowler, Sandra B. Horowitz, Lei Feng, Luis E. Fayad, Swaminathan P Iyer, Michael R Green, Misha Hawkins, Christopher R. Flowers, Sairah Ahmed, Loretta Nastoupil, Sattva S. Neelapu, Yago Nieto, Paolo Strati
Journal: Blood (2021)
Ridd Is Required for the Prevention of Chronic Gvhd By Targeting IRE-1a/Xbp-1s Signaling
Authors: Hee-Jin Choi, Chih-Hang Anthony Tang, Linlu Tian, Yongxia Wu, Mohammed Hanief Sofi, Steven Douglas Schutt, Chih-Chi Andrew Hu, Xue-Zhong Yu
Journal: Blood (2021)
Itolizumab, a Novel Targeted Anti-CD6 Therapy, in Combination with Corticosteroids, Is Well-Tolerated, with Rapid Pharmacodynamic and Clinical Response in Newly Diagnosed Acute Graft-Versus-Host Disease
Authors: John Koreth, Jerome Ritz, Leslie Chinn, Cherie Ng, Lisette M Acevedo, Dalena Chu, Maple Fung, Joel Rothman, Stephen Connelly, Dolca Thomas, Corey Cutler
Journal: Blood (2021)
Abstract PO-003: Predictors for 30-day readmission in patients with pancreatic cancer who had DNR code status
Authors: Jasmeet Kaur, Tanveer Mir, Paramveer Singh, Judie Goodman
Journal: Cancer Research (2021)

Abstract Background: Pancreatic cancer is a lethal malignancy, and most patients present with advanced disease. There is little known about the 30-day readmission rate in patients with Do-not resuscitate (DNR) code status in pancreatic cancer. The study aims to look for predictors for 30-day readmission in pancreatic cancer patients with DNR code status. Methods: This is a retrospective study of a nationally representative cohort of hospitalized admissions admitted from January 1, 2016, to December 31, 2018; 240,107 index pancreatic cancer hospitalizations were recorded. The database was obtained from the Agency for Healthcare Research and Quality’s (AHRQ) Healthcare Cost and Utilization Project (HCUP) national readmission (NRD) dataset files between 2016 – 2018. We examined predictors of death and 30-day readmission among patients with pancreatic cancer who had DNR code status. We evaluated readmission in pancreatic cancer with DNR code status in multivariable Cox hazard regression models. Results: There were 240,107 index hospitalizations with pancreatic cancer (PAC) for the years 2016-2018. There were 51,451 (21.4%) PAC patients who had DNR code status during the index hospitalization. Patients with DNR status had a mean age of 68. The PAC patients with DNR status had significantly higher numbers of inpatient mortality (22% (DNR status) vs 3% (full code) (OR 4.24 (95% CI 3.9-4.6; P &amp;lt;0.001), higher rate of cardiac arrhythmia (26% vs. 19%; p&amp;lt;0.001). The adjusted odd’s ratio (Table 1.) to look for significant readmission predictors for DNR status in PAC included chronic heart failure (OR 1.24, p &amp;lt;0.001), renal failure (OR 1.27, p&amp;lt;.001), and liver disease (OR 2.13, p &amp;lt;0.001). However, patients with diabetes and obesity were found to have a negative association with readmission. Most patients were treated in urban teaching hospitals, and Medicare was the primary payor in 70.4%. Conclusion: In this large nationwide study, we observed higher inpatient mortality and readmission rates in pancreatic cancer who have DNR code status utilizing hospital resources and healthcare costs. This suggests that patients with advanced pancreas cancer who adopt DNR status be offered early hospice care to avoid inpatient mortality. There is a need to look for data based on racial and ethnic differences. Citation Format: Jasmeet Kaur, Tanveer Mir, Paramveer Singh, Judie Goodman. Predictors for 30-day readmission in patients with pancreatic cancer who had DNR code status [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-003.
Equal Access to Hematopoietic Stem Cell Transplant in a Minority-Rich, Ethnically Diverse, Socioeconomically Disadvantaged Population with Peripheral T-Cell Lymphomas at the Montefiore Medical Center/Albert Einstein College of Medicine
Authors: Daniel K. Reef, Alyssa De Castro, Jennat Mustafa, Fariha Khatun, Amanda Lombardo, Latoya Townsend Nugent, Kira Gritsman, Mendel Goldfinger, Noah Kornblum, Aditi Shastri, Ioannis Mantzaris, Lizamarie Bachier-Rodriguez, Amit Verma, Ira Braunschweig, R. Alejandro Sica
Journal: Blood (2021)
Efficient Nanoparticle-Mediated Delivery of Gene Editing Reagents into Human Hematopoietic Stem and Progenitor Cells
Authors: Rkia El Kharrag, Kurt Berckmueller, Margaret Cui, Ravishankar Madhu, Anai M Perez, Olivier Humbert, Hans-Peter Kiem, Stefan Radtke
Journal: Blood (2021)