tbuckley/cabot-search huggingface dataset:
Stable FIX Expression and Durable Reductions in Bleeding and Factor IX Consumption for up to 4 Years Following AMT-060 Gene Therapy in Adults with Severe or Moderate-Severe Hemophilia B
Authors: Wolfgang Miesbach, Karina Meijer, Michiel Coppens, Peter Kampmann, Dr. Klamroth, Roger Schutgens, Giancarlo Castaman, Erhard Seifried, Joachim Schwaeble, Halvard Bönig, Eileen K Sawyer, Frank W.G. Leebeek
Journal: Blood (2019)
Predictive Values of Early ST2 for Acute Graft-Versus-Host Disease and Transplant-Related Complications after Allogeneic Stem Cell Transplantation
Authors: Takuya Miyazaki, Ayako Matsumura, Takayoshi Tachibana, Taiki Ando, Megumi Koyama, Satoshi Koyama, Yoshimi Ishii, Hiroyuki Takahashi, Yuki Nakajima, Ayumi Numata, Wataru Yamamoto, Kenji Motohashi, Maki Hagihara, Kenji Matsumoto, Shin Fujisawa, Hideaki Nakajima
Journal: Blood (2019)
HOUT-02. TREATMENT PATTERNS AND OUTCOMES FOR PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA MULTIFORME IN A US COMMUNITY ONCOLOGY SETTING
Authors: Alex Fu, Nicholas Robert, Trang Pham, Alexander Marshall, Srinivas Annavarapu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND This study aims to describe real world characteristics and outcomes of newly-diagnosed glioblastoma multiforme (GBM) patients in relationship to O6-methylguanine DNA methyltransferase promoter (MGMT) testing and methylation status, in the US. METHODS Patients receiving care for GBM were identified in the US Oncology Network database from 1/1/2013 to 6/30/2018 and followed up to 9/30/2018. Structured data and chart reviews were used to assess demographic and clinical characteristics, treatment patterns, type of surgery, MGMT methylation, and clinical outcomes. RESULTS Of 600 patient charts planned for review, 195 have been randomly selected and reviewed thus far. Of these, 165 (84.6%) had surgical resection and 30 (15.4%) had biopsy only. Eighty-eight (45.1%) patients were tested for MGMT status and 107 (54.9%) were not. Of those tested, 33 (37.5%) were methylated, and 45 (51.1%) unmethylated. Median ages in the overall (including tested and untested), methylated and unmethylated cohorts were 63.7, 58.8, and 66.7 years, respectively. Most common first-line (1L) treatment in overall, methylated, and unmethylated cohorts was radiation concurrent with temozolomide received by 86.2%, 93.9%, and 91.1%, respectively. Median duration of 1L treatment in the overall cohort was 15.1 weeks (95% confidence interval [CI]: 11.9, 21.6) and higher in the methylated vs. unmethylated cohort (25.9 [18.1, 34.6] vs. 15.1 [9.3, 23.4] weeks, p=0.0375). Unadjusted median overall survival and progression-free survival in the overall cohort were 11.4 [9.4, 14.0] months and 5.2 [3.9, 5.8] months, and higher in the methylated vs. unmethylated cohort (20.5 [14.9, not realized] vs. 12.2 [7.1, 17.0] months, p=0.0052, and 9.4 [5.6, 14.0] vs. 5.5 [3.3, 6.8], p=0.0092, respectively). CONCLUSIONS Fewer than half of GBM patients were tested for MGMT methylation in the US community. Clinical outcomes, while better among patients with methylated MGMT, remain poor and current treatment options are limited.
Predicted Leukocyte Telomere Length and Risk of Myeloid Neoplasms
Authors: Jenny Poynter, Spencer Kelley, Marina Marcato, Erica Langer, Anthony J Hooten, Mary Rachel Stimson, Michelle A. Roesler, Phuong L. Nguyen, Adina Cioc, Erica D. Warlick, Nathan Pankratz
Journal: Blood (2019)
Virus‐like particles displaying major house dust mite allergen Der p 2 for prophylactic allergen immunotherapy
Authors: Tewarit Soongrung, Karntichar Mongkorntanyatip, Termsri Peepim, Sirikarn Jitthamstaporn, Patrawadee Pitakpolrat, Theerayuth Kaewamatawong, Christoph M. Janitzek, Susan Thrane, Adam F. Sander, Alain Jacquet
Journal: Allergy (2019)

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The quality of antimicrobial prescribing in acute care hospitals: results derived from a national point prevalence survey, Germany, 2016
Authors: Seven Johannes Sam Aghdassi, Frank Schwab, Sonja Hansen, Luis Alberto Peña Diaz, Michael Behnke, Petra Gastmeier, Tobias Siegfried Kramer
Journal: Eurosurveillance (2019)

BackgroundRobust data on the quality of antimicrobial prescriptions in German acute care hospitals are scarce. To establish and implement antimicrobial stewardship (AMS) measures and to increase prudent antimicrobial use (AMU), the identification of appropriate process and quality indicators is pertinent.AimOur main objective was to identify parameters associated with adequate AMU and inadequate AMU by analysing point prevalence data. Our secondary goal was to describe the current state of AMS implementation in Germany.MethodsA national point prevalence survey for healthcare-associated infections and AMU was conducted in German hospitals in 2016. Data on structure and process parameters were also collected. Recorded antimicrobial prescriptions were divided into adequate, inadequate and undefinable AMU. A multivariable linear regression analysis was performed to examine the correlation of selected structure and process parameters with the adequacy of recorded antimicrobials.ResultsData from 218 acute care hospitals, 64,412 patients and 22,086 administered antimicrobials were included. Multivariable linear regression analysis revealed that documentation of a reason for AMU in the patient notes increased the likelihood of adequate AMU and decreased the likelihood of inadequate AMU significantly (p < 0.001), while tertiary care hospital type had the opposite effect (p < 0.001).ConclusionThrough associating structural and process parameters with adequacy of AMU, we identified parameters that increased the odds of prudent AMU. Documentation was a key element for improving AMU. Revealed deficits regarding the implementation of AMS in German hospitals concerning dedicated staff for AMS activities and establishment of regular AMU training and AMU audits should be tackled.
Primary Pulmonary Hypertension
Authors: Lewis J. Rubin
Journal: New England Journal of Medicine (1997)

Primary pulmonary hypertension is a condition characterized by sustained elevations of pulmonary-artery pressure without a demonstrable cause. The diagnostic criteria used in the National Institutes of Health (NIH) registry1 include a mean pulmonary-artery pressure of more than 25 mm Hg at rest, or more than 30 mm Hg with exercise, and the exclusion of left-sided cardiac valvular disease, myocardial disease, congenital heart disease, and any clinically important respiratory, connective-tissue, or chronic thromboembolic diseases. Pulmonary vascular disease with clinical and pathological features similar to those of primary pulmonary hypertension can occur in patients with portal hypertension,2 infection with the human immunodeficiency . . .
2019 American Heart Association Focused Update on Systems of Care: Dispatcher-Assisted Cardiopulmonary Resuscitation and Cardiac Arrest Centers: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
Authors: Ashish R. Panchal, Katherine M. Berg, José G. Cabañas, Michael C. Kurz, Mark S. Link, Marina Del Rios, Karen G. Hirsch, Paul S. Chan, Mary Fran Hazinski, Peter T. Morley, Michael W. Donnino, Peter J. Kudenchuk
Journal: Circulation (2019)

Survival after out-of-hospital cardiac arrest requires an integrated system of care (chain of survival) between the community elements responding to an event and the healthcare professionals who continue to care for and transport the patient for appropriate interventions. As a result of the dynamic nature of the prehospital setting, coordination and communication can be challenging, and identification of methods to optimize care is essential. This 2019 focused update to the American Heart Association systems of care guidelines summarizes the most recent published evidence for and recommendations on the use of dispatcher-assisted cardiopulmonary resuscitation and cardiac arrest centers. This article includes the revised recommendations that emergency dispatch centers should offer and instruct bystanders in cardiopulmonary resuscitation during out-of-hospital cardiac arrest and that a regionalized approach to post-cardiac arrest care may be reasonable when comprehensive postarrest care is not available at local facilities.
Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis: Multi-site study
Authors: Tetsuo Shoda, Ting Wen, Julie M. Caldwell, Margaret H. Collins, John A. Besse, Garrett A. Osswald, J. Pablo Abonia, Nicoleta C. Arva, Dan Atkins, Kelley E. Capocelli, Evan S. Dellon, Gary W. Falk, Nirmala Gonsalves, Sandeep K. Gupta, Ikuo Hirano, Vincent A. Mukkada, Philip E. Putnam, Rachel M. Sheridan, Amanda K. Rudman Spergel, Jonathan M. Spergel, Joshua B. Wechsler, Guang-Yu Yang, Seema S. Aceves, Glenn T. Furuta, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2019)
Identification of Dual Positive CD19+/CD3+ T Cells in an Apheresis Product Undergoing Chimeric Antigen Receptor (CAR) Transduction
Authors: Liora M Schultz, Shabnum Patel, Sneha Ramakrishna, Alice Bertaina, Neehar Bhatia, Jean Oak, Robbie G. Majzner, Christina Baggott, Kara L. Davis, Crystal L. Mackall, Steven A Feldman
Journal: Blood (2019)
GENE-56. MENINGIOMA GENOMIC SUBGROUP AS A PREDICTOR OF POST-OPERATIVE PATIENT OUTCOMES: IMPLICATIONS FOR TREATMENT AND FOLLOW-UP
Authors: Mark Youngblood, Amar Sheth, Amy Zhao, Julio Montejo, Daniel Duran, Chang Li, Evgeniya Tyrtova, Koray Özduman, Matthieu Peyre, Julien Boetto, Sacit Omay, Michel Kalamarides, E Zeynep Erson-Omay, Murat Günel, Jennifer Moliterno
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Meningiomas can be classified into six genomic subgroups based on mutations in NF2, SMARCB1, KLF4, POLR2A, or activating variants in the PI3K or Hedgehog signaling pathways. Previous work has identified specific associations of driver events with clinical and molecular features, such as tumor location. However, their utility in predicting post-operative patient outcomes is not well-explored. Similar to recently described epigenetic signatures, underlying genomic subgroup may provide prognostic value in meningioma management. METHODS Targeted sequencing data was used to classify over 500 meningiomas into established genomic subgroups, and available patient outcome data was assembled based on retrospective chart reviews. Collected data included recurrence (based on imaging), extent of resection (EOR), use of post-operative radiation, and radiologic follow-up period. Statistical associations between genomic subgroup and recurrence were assessed using Fisher’s exact, Kaplan-Meier, and Cox proportional hazards modeling, including stratification based on use of radiation, EOR, grade, and location. RESULTS Meningiomas in the PI3K subgroup exhibited higher rates of early recurrence during the first five post-operative years. This subgroup affiliation was found to be an independent predictor of recurrence free survival from Ki-67, grade, and other clinical features. By contrast, recurrence was rare in the POLR2A, SMARCB1, and KLF4 subgroups, and was typically associated with use of post-operative radiation in these cases. The longest average recurrence free survival was observed in POLR2A mutant meningiomas. CONCLUSIONS Our analysis identifies divergence in meningioma patient outcomes based on genomic subgroup and suggests patients with PI3K activating events may require closer surveillance. These tumors, which often occur near and encase critical neurovascular structures along the sphenoid wing, may further benefit from consideration of radiation and emerging precision therapies. Conversely, other subgroups rarely recur, suggesting caution be invoked with use of potentially morbid adjuvant treatment.
CBMT-25. THE KLF4K409Q MUTATION IN MENINGIOMA IMPAIRS HIF-1Α DEGRADATION AND CAN BE HARNESSED FOR TARGETED THERAPY
Authors: Niklas von Spreckelsen, Natalie Waldt, Rebecca Poetschke, Christoph Kesseler, Hildegard Dohmen, Hui-Ke Jiao, Attila Nemeth, Martina Deckert, Frank Angenstein, Boris Krischek, Pantelis Stavrinou, Marco Timmer, Marc Remke, Elmar Kirches, Roland Goldbrunner, Ennio Chiocca, Stefan Huettelmaier, Till Acker, Christian Mawrin
Journal: Neuro-Oncology (2019)

Abstract Recently, several Non-NF2 driver mutations (KLF4, TRAF7, SMO, AKT1E17K) in meningioma have been identified. While they have been shown to correlate with certain pathological subtypes and locations, the clinical impact and repercussions on cellular pathways have largely remained elusive. Through analysis of clinical, pathological and preoperative imaging data of 96 patients and sequencing of the corresponding 96 tumor samples for the Krueppel like factor 4-K409Q mutation (KLF4K409Q) we present evidence that the KLF4K409Q tumors harbour an increased risk for peritumoral brain edema (PTBE) and can be predicted with the edema-index, a simple tool based on preoperative imaging. Further analysis involving RNA-sequencing of a matched subset of 7 KLF4K409Q and 10 KLF4-wildtype (wt) tumors revealed a significant shift of gene expression and the upregulation of hypoxia driven pathways, including VEGF levels, in KLF4K409Q tumors. On the cellular level, we go on to show that the KLF4K409Q mutation results in an increased KLF-4 stability as well as the inhibition of hydroxylation dependent degradation of HIF1-α and a significant increase of VEGF expression under hypoxic conditions. Finally, we demonstrate that this upregulation of VEGF in KLF4K409Q cells can be inhibited by targeting the mammalian target of rapamycin (mTor) with Temsirolimus. In summary we show that the KLF4K409Q mutation in meningioma has highly relevant repercussions in both, the biological and clinical context and can be harnessed for targeted therapy.
Structural OCT Signs Suggestive of Subclinical Nonexudative Macular Neovascularization in Eyes with Large Drusen
Authors: Callum Narita, Zhichao Wu, Philip J. Rosenfeld, Jin Yang, Cancan Lyu, Emily Caruso, Myra McGuinness, Robyn H. Guymer
Journal: Ophthalmology (2019)
The First Functional HLA-a*01:01-Restricted EBV-LMP2-Specific T-Cell Receptors for TCR Gene Therapy of Patients with EBV-Associated Type II/III Malignancies
Authors: Wesley Huisman, Ilse Gille, Lieve E. van der Maarel, Lois Hageman, Rob C.M. de Jong, Derk Amsen, Fred Falkenburg, Inge Jedema
Journal: Blood (2019)
A Phase II Trial to Compare Allogeneic Transplant Vs. Standard of Care for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Protocol 1503
Authors: Mary Eapen, Donna S Neuberg, Adam M. Mendizabal, Kristen E. Stevenson, Joseph H. Antin, Nancy DiFronzo, Fuad A El Rassi, Premal Lulla, Edmund K. Waller, Jamie Garrison, Shannon Smith, Keith Sullivan, Mark C. Walters, Lakshmanan Krishnamurti
Journal: Blood (2019)
STEM-23. METASTATIC BRAIN TUMOR IMAGING THROUGH TARGETED PEPTIDES ISOLATED VIA PHAGE DISPLAY BIOPANNING AGAINST BRAIN METASTASIS-INITIATING CELLS
Authors: JongMyung Kim, James Liu
Journal: Neuro-Oncology (2019)

Abstract To effectively target metastatic brain tumors (MBTs), the paradigm of initiating treatment against MBTs following detection on clinical imaging needs to be shifted to an understanding of the mechanisms that drive the formation and maintenance of brain metastasis-initiating cells (BMICs). Targeting this tumor sub-population, which may form as a result of activation of the epithelial-mesenchymal transition, may allow for more effective means of understanding and targeting brain metastases. In order to isolate BMICs, we have harvested cells from patient derived MBTs originating from lung cancer and cultured the cells using stem cell media conditions. We then performed in vitro and in vivo phage display biopanning to isolate 12-amino acid length peptides that specifically target BMICs. Several peptides were isolated from both in vitro and in vivo biopanning strategies. Of the peptides recovered, one peptide, LBM4, demonstrated specific binding to MBT cells over primary lung cancer cells in vitro through flow cytometry analysis and immunocytochemistry. Fluorescent tagged LBM4 intravenously injected into mice harboring intracranial brain metastases demonstrated peptide localization to the tumor within the intracranial cavity visualized with live animal imaging. Peptide imaging of tumor corresponded to MRI imaging confirming that the peptides could serve as an alternative to tumor imaging, with the potential for greater sensitivity resulting from the cellular targeting of MBTs. Our results demonstrate that we can use a combination of in vitro and in vivo phage display biopanning to isolate cell specific targeting peptides. MBT targeting peptides can potentially result in a shifting of the clinical treatment paradigm of brain metastases, through the development of more effective targeted therapeutics aimed at BMICs, as well as improving detection of MBT cells which may result in earlier tumor visualization, as well as delineation of tumor recurrence versus radiation effects.
Intracranial Hemorrhage in Egyptian Children with Primary Immune Thrombocytopenia (ITP): Report of 24 Cases in 20 Years
Authors: Mohsen Saleh Elalfy, Mohamed Ahmed Badr, Ahmed Mansour, Tamer Hassan, Mohamed Meabed, Hoda Hassab, Mahmoud Elhawy, Ilham Youssry, Marwa AbdelHady, Mohamed Elshanshory, Omar Elalfy, Marwa Wahid, Khalid Elsayh
Journal: Blood (2019)
Stroke Risk in Blood or Marrow Transplant (BMT) Survivors - a Report from the BMT Survivor Study (BMTSS)
Authors: Radhika Gangaraju, Yanjun Chen, Lindsey Hageman, Jessica Wu, Wendy Landier, Liton F. Francisco, Andrew McDonald, Donna Murdaugh, Michelle Kung, Emily Ness, Daniel J. Weisdorf, Stephen J Forman, Lennie Wong, Mukta Arora, Saro H. Armenian, Smita Bhatia
Journal: Blood (2019)
EXTH-09. FIRST-IN-HUMAN DOSING CONSIDERATIONS OF A BISPECIFIC ANTIBODY FOR TREATING GLIOBLASTOMA
Authors: Teilo Schaller, Matthew Foster, Ivan Spasojevic, Patrick Gedeon, Luis Sanchez-Perez, John Sampson
Journal: Neuro-Oncology (2019)

Abstract Current therapy for glioblastoma (GBM) is incapacitating and limited by non-specific toxicity to the surrounding brain. We have developed an immunotherapeutic approach that selectively targets GBM by redirecting the patients’ own T cells towards the tumor in an antigen-specific manner using a bispecific antibody. Our novel bispecific antibody (“BRITE”) binds GBM-specific surface marker EGFRvIII and the CD3 receptor on T cells, resulting in crosslinking and tumor-specific cell lysis. We previously showed in patient-derived and syngeneic murine glioma models, that treatment with BRITE leads to long-term survival in mice with glioblastoma. A pharmacokinetic analysis in a CD3 humanized mouse revealed that BRITE in plasma and whole blood has an initial half-life of ~8 minutes and a terminal half-life of ~2.5 hours. Given our preclinical success, we have initiated clinical trial-enabling studies, including studies of BRITE toxicology and GMP manufacturing of drug product. A crucial consideration for our proposed Phase 1 dose escalation trial is the starting dose in humans. To this end, we utilized the FDA-recommended minimum anticipated biological effect level (MABEL) of BRITE – a holistic approach that considers all available in vitro and in vivo data – to calculate the first-in-human starting dose of BRITE.
Small Molecule-Induced, Selective STAT3 Degradation Leads to Anti-Tumor Activity in STAT3-Dependent Heme Malignancies
Authors: Fred Csibi, Nan Ji, Bin Yang, Karen Yuan, Michele Mayo, Haojing Rong, Scott Rusin, Kirti Sharma, Christine Loh, Henry Li, Sharon Townson, Jesse Chen, Hari Kamadurai, Duncan Walker, Jared Gollob, Nello Mainolfi
Journal: Blood (2019)
CBMT-43. INTEGRATED LIPIDOMIC AND MOLECULAR ANALYSIS REVEALS A SUBSET OF GLIOBLASTOMA VULNERABLE TO FERROPTOSIS
Authors: Danielle Morrow, Nicholas Bayley, Kevin Williams, Hayato Muranaka, Robert Prins, Linda Liau, Timothy Cloughesy, Steven Bensinger, David Nathanson
Journal: Neuro-Oncology (2019)

Abstract Cancers, including the universally lethal glioblastoma (GBM), have reprogrammed lipid metabolism to fuel tumor growth. However, the molecular alterations responsible for aberrant lipid metabolism, and the potential for identifying new therapeutic opportunities are not fully understood. To systematically investigate the GBM lipidome, we performed integrated transcriptomic, genomic and shotgun lipidomic analysis of a library of molecularly diverse patient-derived GBM cells (n=30). Using this comprehensive approach, we discovered two GBM sub-groups defined by their combined molecular and lipidomic profile. Polyunsaturated fatty acids (PUFAs) were among the most significant lipids that distinguished these two groups of GBM tumors. Intriguingly, this lipid metabolic phenotype was associated with heightened sensitivity to ferroptosis – a newly discovered form of regulated cell death. As PUFA oxidation is a critical feature of ferroptosis, our findings suggest a novel association between specific molecular signatures of GBM, lipid metabolism and ferroptosis. This relationship may present a new therapeutic opportunity to target ferroptosis in a molecularly-defined subset of GBMs.
Assessment of Response to Neoadjuvant Chemoradiotherapy by 18F-FDG PET/CT in Patients With Locally Advanced Esophagogastric Junction Adenocarcinoma
Authors: Nuria Sánchez-Izquierdo, Pilar Perlaza, Mario Pagès, Elvira Buxó, José Rios, Domenico Rubello, Patrick M. Colletti, Maria Mayoral, Sebastian Casanueva, Gloria Fernández-Esparrach, Angels Ginés, David Fuster
Journal: Clinical Nuclear Medicine (2019)

Purpose The outcome of locally advanced adenocarcinoma of the esophagogastric junction (AEG) treated with preoperative chemoradiotherapy is heterogeneous, and favorable response to this treatment is a key factor in the patient's prognosis. The aim of this study was to evaluate 18 F-FDG PET/CT in assessing metabolic response in patients with AEG. Materials and Methods This prospective study evaluated all consecutive patients with potentially operable locally advanced AEG who were candidates for neoadjuvant chemoradiotherapy. PET/CT and contrast-enhanced thoracoabdominal CT were performed at baseline and 2 weeks after completion of chemoradiotherapy for response evaluation. The response rate was assessed using Response Evaluation Criteria in Solid Tumors criteria for contrast-enhanced thoracoabdominal CT and Positron Emission Tomography Response Criteria in Solid Tumors criteria for PET/CT. The regression rate was assessed using a 5-grade histopathology scoring system of the surgically resected tumor. Metastatic lesions were confirmed by histopathology examination or imaging and clinical follow-up at 6 months. Results A total of 40 cases were finally included in the study. Distant metastases were found in the baseline PET/CT in 6 of 40 cases (retroperitoneal [2] or mediastinal/hiliar [1] lymph nodes and liver [2] or bone [1] metastases) and were therefore excluded from surgery. Pathologic response correlated with the ΛSUV max threshold of ≤45% ( P = 0.033). CT response correlated well with both the baseline SUV max ( P = 0.039) and the ΛSUV max ( P = 0.001). Five-year survival curves for AEG correlated with the ΛSUV max using a threshold of ≤45% for both progression-free and overall survival. Conclusions 18 F-FDG PET/CT is useful for diagnosing nonsuspected metastasis before neoadjuvancy in potentially operable AEG. The ΛSUV correlates with pathologic response and is a long-term independent prognostic factor of survival.