tbuckley/cabot-search huggingface dataset:
The Relationship between Molecular Response of BCR-ABL1 Transcripts within 6 Months and Deep Molecular Response at 18 Months to Dasatinib Treatment for Newly Diagnosed Patients with CML-CP
Authors: Daigo Michimata, Kazunori Murai, Yasuro Miyairi, Yoshiaki Okano, Yuuzou Suzuki, Hiroyuki Hamada, Akiyoshi Sato, Tatsuo Oyake, Shugo Kowata, Yasuhiko Tsukushi, Norifumi Sugawara, Akihiro Otsu, Kenji Shimosegawa, Shigeki Ito, Yoji Ishida
Journal: Blood (2019)
Prosthetic Heart Valves
Authors: Wanpen Vongpatanasin, L. David Hillis, Richard A. Lange
Journal: New England Journal of Medicine (1996)

Since the 1950s more than 80 models of prosthetic heart valves have been developed and used. More than 60,000 valve replacements are performed annually in the United States. Prosthetic heart valves may be mechanical or bioprosthetic. Mechanical valves, which are composed primarily of metal or carbon alloys, are classified according to their structure as caged-ball, single-tilting-disk, or bileaflet-tilting-disk valves. Bioprostheses may be heterografts, which are composed of porcine or bovine tissue (pericardial or valvular) mounted on a metal support, or homografts, which are preserved human aortic valves. The most commonly used prosthetic valves are listed in Table 1 and illustrated in Figure 1. . . .
Isavuconazole Prophylaxis during Early Phases of Allogeneic HSC Transplantation Is Not Associated to an Increase Need of Cyclosporin-a Dose Modification
Authors: Alessandra Cupri, Salvatore Leotta, Uros Markovic, Maria Grazia Camuglia, Giulio Antonio Milone, Angelo Curto Pelle, Valerio Leotta, Mary Ann Di Giorgio, Anna Bulla, Di Marco Anna Lia, Gaetano Moschetti, Giuseppe Milone
Journal: Blood (2019)
NIMG-64. IMPACT OF TUMOR LOCATION ON IMAGE-DERIVED VOLUME, PROLIFERATION RATE AND GROWTH VELOCITY IN GLIOBLASTOMA PATIENTS
Authors: Julia Lorence, Kristin Swanson, Cassandra Rickertsen, Sara Ranjbar, Sandra Johnston, Kyle Singleton, Alyx Porter, Bernard Bendok, Ross Mitchell, Joshua Rubin, Leland Hu, Haylye White, Paula Whitmire, Maciej Mrugala
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant primary brain tumor in adults with a median overall survival (OS) of 15months. Despite advancements in treatments, prognosis is dismal and the prognostic significance of tumor location is not entirely understood. METHODOLOGY: In our study, we investigated sex-specific volumetric, tumor growth kinetics, and outcome differences among GBMs in various brain locations. Primary GBM patients with pretreatment magnetic resonance imaging (MRI) data (N=289, 173 males, 116 females) were selected from our brain tumor repository. Tumor abnormality was segmented on T1-weighted post-gadolinium contrast agent (T1Gd) MRIs. We utilized the Harvard-Oxford brain atlases to determine the location of GBMs. RESULTS Overall, our study found smaller tumors in the left hemisphere. This may be expected as left-hemispheric GBM symptoms could present earlier, leading to earlier diagnosis and treatment. However, when the cohort was split by sex, we found this observation significant for females only in the parietal lobe (p &lt; 0.0001). Further, female GBMs demonstrated smaller necrotic volume in the left hemisphere (p = 0.030). Sex-specific differences in incidence were noted in the temporal and occipital lobes (2M:1F). Comparing tumor growth kinetics in different brain locations and hemispheres, females had significantly lower tumor proliferation rates in the left hemisphere (p = 0.009) and lower tumor proliferation rates in the left frontal lobe (p = 0.031). Controlling for treatment, patients with frontal lobe tumors had significantly longer OS compared to those with GBMs in the temporal lobe (p = 0.046, 312 days). Differences in growth velocities were noted between frontal and parietal lobe with frontal GBMs having lower velocities in comparison to parietal lobe GBMs. CONCLUSION Together, our results demonstrate that tumor growth and proliferation rates may vary based on location and sex. Additional research is needed to further explore the clinical significance of tumor location.
RTHP-01. PENTOXIFYLLINE AND VITAMIN E FOR THE TREATMENT OF RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY
Authors: Lisa Sudmeier, Jeffrey Switchenko, Bree Eaton, Hui-Kuo Shu
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The combination of oral pentoxifylline (Ptx) and vitamin E (VitE) has been used to treat radiation-induced fibrosis and soft tissue injury. A 2008 study showed an average decrease in edema with the use of Ptx + VitE in 11 patients with suspected radiation necrosis after stereotactic radiosurgery (SRS). Here we review outcomes in patients prescribed Ptx + VitE at our institution for the treatment of radiation necrosis. METHODS 48 patients were included in this analysis. All patients were treated with SRS, had evidence of radiation necrosis, and had MR imaging before and after starting Ptx + VitE. The radiation oncologist’s impression of the imaging in the electronic medical record was used to score response to treatment. Official radiology reports were also reviewed. RESULTS 43.8% of patients showed evidence of improvement, 18.8% showed no change, and 25% showed worsening radiation necrosis on imaging after starting Ptx + VitE. One patient had a mixed response; 5 patients (10.4%) had disease progression. The median time to response assessment after starting Ptx + Vit E was 3.17 months. 9 patients progressed significantly on Ptx + VitE and required Bevacizumab, hyperbaric oxygen therapy or surgery. Patients who had multiple lesions treated with SRS were less likely to show improvement on imaging after Ptx + VitE (p=0.037). 34 patients were also prescribed dexamethasone, either before (7), with (16), or after starting (11) Ptx + VitE. Use of dexamethasone was not associated with improved response to Ptx + VitE (p=0.471). 3 patients stopped Ptx + VitE due to reported side effects. CONCLUSION Ptx + VitE appears safe for the treatment of radiation necrosis, but randomized data are needed to assess efficacy.
STEM-11. CD146/MCAM REGULATES MESENCHYMAL PROPERTIES, STEMNESS, RADIO-RESISTANCE AND YAP ACTIVITY IN GLIOBLASTOMA
Authors: Yuan-Ke Liang, Daniëlle Voshart, Wilfred den Dunnen, Lara Barazzuol, Frank Kruyt
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM), a highly malignant and lethal brain tumor, is characterized by diffuse invasion into the brain and chemoradiotherapy resistance resulting in recurrences and poor prognosis. In this study we examined if the cell adhesion molecule CD146/ MCAM is contributing to the malignant properties of GBM, as it is known to have multiple protumorigenic functions in other tumor types. TCGA GBM database analyses revealed enhanced levels of CD146 in GBM compared to normal brain. A panel of patient-derived GBM spheroids, enriched for GBM stem cells (GSC), displayed variable and modest expression of CD146 that was strongly enhanced by cell adherence mediated by serum differentiation or ECM-coating. TGF-β-induced mesenchymal transition in U87 cells was accompanied by induction of CD146 expression, whereas ectopic overexpression of CD146/GFP in GG16 spheroids increased mesenchymal marker expression and cell invasion. Conversely, CRISPR/Cas9-generated CD146 knockouts in GSC23 spheroids led to reduced mesenchymal marker expression and invasion. These results were confirmed by applying embryonic stem cell-derived brain organoids as models to study invasion. Hence, GBM spheroid - brain organoid fusions demonstrated a stimulatory function of CD146 on invasion. Moreover, stem cell marker expression and clonogenic assays showed that CD146 increases the stem cell potential of GBM cells. The CD146 ectopic overexpression and knockout models also demonstrated involvement of CD146 in resistance to radiation that could be mechanistically linked with CD146-dependent suppression of p53 accumulation and activation of NF-kB. Interestingly, exploration of additional mechanisms potentially involved in CD146 functioning, led to the discovery that the oncogenic protein Yes-associated protein (YAP) is also regulated by CD146. Together, our findings demonstrate the importance of CD146 in controlling tumor aggressiveness and radioresistance in GBM cells.
SP0049 CASE 1 DISCUSSANT: DISCUSSION OF HOW ANALGESIC USE RARELY PROVIDES COMPLETE PAIN RELIEF, IS NOT SUFFICIENT TO ENABLE ACTIVITY, MAY BE A BARRIER TO ACTIVITY, AND CAN DETRACT FROM OTHER EFFECTIVE INTERVENTIONS
Authors: Silje Halvorsen Sveaas
Journal: Annals of the Rheumatic Diseases (2019)

<h3>All these painkillers and still not going anywhere:</h3> Pain is the cardinal symptom of rheumatic diseases, and is reported as the most important health aspect for this patient group.<sup>1</sup> Hence, analgesics is a part of the management for many patients with rheumatic diseases. Pain may be a barrier for physical activity, <sup>2</sup> and patients with rheumatic diseases is reported to have a lower physical activity level than the general population.<sup>3</sup> At the same time, it is well known that physical activity has many benefits for this patient group. Physical activity may lower the burden of the disease<sup>4</sup>, may prevent co-morbidities such as cardiovascular diseases, diabetes and osteoporosis, and has beneficial effects on psychological health.<sup>2,3</sup> The aim of this lesson will be to present a case history of a patient with extensive pain problems and discuss the treatment options based on relationship between analgesics, pain and physical activity. <h3>Objectives:</h3> · To discuss the effect of analgesics on activity · To discuss the use of painkillers in connection with exercise · To discuss pain tolerance during exercise · To discuss the effect of physical activity on pain <h3>References:</h3> [1] Heiberg T, Lie E, van der Heijde D, Kvien TK. Sleep problems are of higher priority for improvement for patients with ankylosing spondylitis than for patients with other inflammatory arthropathies. Ann Rheum Dis. 2011;70(5):872-873. [2] Rausch Osthoff AK, Niedermann K, Braun J, et al. 2018 EULAR recommendations for physical activity in people with inflammatory arthritis and osteoarthritis. Ann Rheum Dis. 2018;77(9):1251-1260. [3] Cook MJ, Bellou E, Bowes J, et al. The prevalence of co-morbidities and their impact on physical activity in people with inflammatory rheumatic diseases compared with the general population: results from the UK Biobank. Rheumatology (Oxford, England). 2018;57(12):2172-2182. [4] Sveaas SH, Smedslund G, Hagen KB, Dagfinrud H. Effect of cardiorespiratory and strength exercises on disease activity in patients with inflammatory rheumatic diseases: a systematic review and meta-analysis. Br. J. Sports Med. 2017;51(14):1065-1072. <h3>Disclosure of Interests:</h3> None declared
Association of Donor-Recipient HLA Matching with Outcome of Unrelated Donor Hematopoietic Stem Cell Transplantation: A Study from the Cellular Therapy and Immunobiology Working Party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Annalisa Ruggeri, Carlheinz Mueller, Liesbeth C. de Wreede, Junfeng Wang, Lotte Wieten, Luca Vago, Jorinde Hoogenboom, Gerard Socie, Riitta Niittyvuopio, Ibrahim Yakoub-Agha, Charles R Crawley, Eleni Tholouli, Claude-Eric Bulabois, Goda Choi, Edouard Forcade, Anne Huynh, Stig Lenhoff, Virginie Gandemer, Fabio Ciceri, Nicolaus Kröger, Xavier Leleu, Maija Itälä-Remes, Vanderson Rocha, Chiara Bonini, Christian Chabannon, Katharina Fleischhauer
Journal: Blood (2019)
A Multicenter Study of Ibrutinib Resistance Development and Intervention with Venetoclax in Patients with Chronic Lymphocytic Leukemia
Authors: Kerry A Rogers, Lai Wei, Seema A. Bhat, Dan Jones, Erlene K. Seymour, Deborah M. Stephens, J Christine Ye, John C. Byrd, Jennifer Woyach
Journal: Blood (2019)
Manipulation of Induced Foxp3+ Regulatory T Cells for Prevention of Mouse Acute Graft-Versus-Host Disease
Authors: Tzeon-Jye Chiou, Yi-Chun Ke, Chun-Tse Kuo, Hsiu-Yuan Huang, Shao-Chun Lu, Sin-Tak Chu, Woan-Fang Tzeng
Journal: Blood (2019)
Betacellulin drives therapy resistance in glioblastoma
Authors: Qiwen Fan, Zhenyi An, Robyn A Wong, Xujun Luo, Edbert D Lu, Albert Baldwin, Manasi K Mayekar, Franziska Haderk, Kevan M Shokat, Trever G Bivona, William A Weiss
Journal: Neuro-Oncology (2019)

The transcription factor signal transducer and activator of transcription 3 (STAT3) drives progression in glioblastoma (GBM), suggesting STAT3 as a therapeutic target. Surprisingly however, GBM cells generally show primary resistance to STAT3 blockade.Human glioblastoma cell lines LN229, U87, SF767, and U373, and patient-derived xenografts (PDXs) GBM8 and GBM43 were used to evaluate epidermal growth factor receptor (EGFR) activation during STAT3 inhibition. Protein and gene expression experiments, protein stability assays, cytokine arrays, phospho-tyrosine arrays and EGFR-ligand protein arrays were performed on STAT3 inhibitor-treated cells. To evaluate antitumor activity, we administered a betacellulin (BTC)-neutralizing antibody alone and in combination with STAT3 inhibition. BTC is an EGFR ligand. We therefore treated mice with orthotopic xenografts using the third-generation EGFR inhibitor osimertinib, with or without STAT3 knockdown.We demonstrate that both small-molecule inhibitors and knockdown of STAT3 led to expression and secretion of the EGFR ligand BTC, resulting in activation of EGFR and subsequent downstream phosphorylation of nuclear factor-kappaB (NF-κB). Neutralizing antibody against BTC abrogated activation of both EGFR and NF-κB in response to inhibition of STAT3; with combinatorial blockade of STAT3 and BTC inducing apoptosis in GBM cells. Blocking EGFR and STAT3 together inhibited tumor growth, improving survival in mice bearing orthotopic GBM PDXs in vivo.These data reveal a feedback loop among STAT3, EGFR, and NF-κB that mediates primary resistance to STAT3 blockade and suggest strategies for therapeutic intervention.
A Network Meta-Analysis (NMA) to Evaluate Comparative Effectiveness of Frontline Treatments for Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Who Are Transplant-Ineligible (TIE)
Authors: Thierry Facon, Jesús San-Miguel, Saad Z. Usmani, Meletios A. Dimopoulos, Shaji K. Kumar, Maria-Victoria Mateos, Michele Cavo, Bart Heeg, Sophie Van Beekhuizen, Marta Pisini, Sandhya Nair, Annette Lam, Mary Slavcev, Jianming He
Journal: Blood (2019)
ATIM-32. PREDICTORS OF IMPROVED SURVIVAL FOLLOWING ONCOLYTIC VIRUS TREATMENT IN PATIENTS WITH RECURRENT GLIOBLASTOMA: GENE EXPRESSION ANALYSIS FROM THE PHASE IB G207 CLINICAL TRIAL
Authors: Kevin Cassady, Katherine Miller, Nripesh Prasad, Dragan Maric, Josh Bernstock, Justin Roth, Naomi Barker, Jennifer Coleman, Kathleen Schieffer, Kristen Leraas, Anthony Miller, Jianmei Leavenworth, Gary Cutter, Richard Whitley, Bernard Roizman, G Yancey Gillespie, Elaine Mardis, James Markert
Journal: Neuro-Oncology (2019)

Abstract Our Phase I trials of experimental virotherapy for recurrent glioblastoma (GBM) have shown that inoculation with a conditionally replication-competent early generation oncolytic herpes simplex virus (oHSV), G207, is safe. However, while 17 of 37 subjects experienced objective clinical responses, the highly attenuated oHSV did not uniformly improve survival. We sought to identify predictors that would identify mechanisms contributing to survival and improve future trial design, by studying accrued samples. We analyzed pre-treatment biopsy and post-G207-treatment tumor samples (collected D2-5 post injection) banked from the patients enrolled in the phase IB G207 trial. The key findings from these patients suggest that productive G207 infection and G207-induced changes in gene expression were predictive of oHSV therapeutic success. RNAseq-based transcriptome analysis of these samples revealed that both the intrinsic IFN mediated antiviral response and adaptive immune functional response in patients correlated significantly with improved survival following G207 inoculation. Further, GBM tissue stained using multiplex fluorescent immunohistochemistry supported differences in the tumor microenvironments that were identified from RNAseq data analysis. Our data indicate that both viral gene expression and the resulting intrinsic anti-viral and recruited adaptive response were critical for survival after G207 inoculation and predict survival with this early generation oHSV in patients with recurrent malignant glioma.
Donor Clonal Hematopoiesis Increases Risk of Acute Graft Versus Host Disease after Matched Related Transplantation in AML and MDS Patients
Authors: Betul Oran, Richard E. Champlin, Feng Wang, Nikeshan Jeyakumar, Guillermo Garcia-Manero, Hagop M. Kantarjian, Rima M. Saliba, Kai Cao, Elizabeth J. Shpall, Amin M. Alousi, Rohtesh S. Mehta, Uday Popat, Andy Futreal, Koichi Takahashi
Journal: Blood (2019)
ACTR-45. FATTY ACID SYNTHASE INHIBITOR TVB-2640 INCREASES PROGRESSION FREE SURVIVAL IN RECURRENT GBM
Authors: Brandon Konkel, Joel Michalek, Enrique Diaz Duque, Qiangia Liu, Laura Caflisch, Vinu Madhu, Andrew Brenner
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Standard of care for glioblastoma (GBM) is surgical resection followed by temozolamide, with bevacizumab (bev) given at relapse. Responses to bev remain brief; resistance may involve overexpression of Fatty Acid Synthase (FASN). METHODS This is a prospective phase 2 study of bev with TVB-2640 in patients with rGBM at first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age ≥ 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. An exploratory phase randomization into 2 separate arms of single agent bev or in combination with TVB-2640 with MR-Spectroscopy (MRS) and serum sampling for exosome analysis obtained on all patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converged to a single arm and continue to receive bev in combination with TVB-2640. A total sample size of 24 patients will provide 90% power to detect a 4 month difference in PFS (3–4 months for Bev alone (historic controls) (i.e., a hazard ratio of 0.43) using a one-sided log-rank test with alpha=0.1. RESULTS Enrollment is complete with 28 patients to date. 3 failed screening. 21 came off study and 4 are active. No grade 4 or higher treatment-related AEs have occurred, with Grade 3 events included 3 cases of palmar-plantar erythrodysesthesia; 1 each of hypertension, stomatitis, optic neuritis, DVT, and wound infection. 95.2% of patients have achieved at least stable disease by RANO Criteria, with a 66.7% overall response rate (ORR). Median time to progression was 5.9, which is statistically superior to historical controls. Overall survival as well as biomarker analysis (exosome, MRS), is pending. CONCLUSIONS The combination of TVB2640 with bev appears well tolerated and with PFS6 significantly improved over historical controls. Final data analysis as well as exploratory biomarker analysis will be presented.
Suctioning versus traditional minimally invasive percutaneous nephrolithotomy to treat renal staghorn calculi: A case-matched comparative study
Authors: Zewu Zhu, Yu Cui, Huimin Zeng, Yongchao Li, Cheng He, Jinbo Chen, Feng Zeng, Yang Li, Zhiyong Chen, Hequn Chen
Journal: International Journal of Surgery (2019)
A Listeria monocytogenes Bacteriocin Can Target the Commensal Prevotella copri and Modulate Intestinal Infection
Authors: Nathalie Rolhion, Benoit Chassaing, Marie-Anne Nahori, Jana de Bodt, Alexandra Moura, Marc Lecuit, Olivier Dussurget, Marion Bérard, Massimo Marzorati, Hannah Fehlner-Peach, Dan R. Littman, Andrew T. Gewirtz, Tom Van de Wiele, Pascale Cossart
Journal: Cell Host & Microbe (2019)

Understanding the role of the microbiota components in either preventing or favoring enteric infections is critical. Here, we report the discovery of a Listeria bacteriocin, Lmo2776, which limits Listeria intestinal colonization. Oral infection of conventional mice with a Δlmo2776 mutant leads to a thinner intestinal mucus layer and higher Listeria loads both in the intestinal content and deeper tissues compared to WT Listeria. This latter difference is microbiota dependent, as it is not observed in germ-free mice. Strikingly, it is phenocopied by pre-colonization of germ-free mice before Listeria infection with Prevotella copri, an abundant gut-commensal bacteria, but not with the other commensals tested. We further show that Lmo2776 targets P. copri and reduces its abundance. Together, these data unveil a role for P.copri in exacerbating intestinal infection, highlighting that pathogens such as Listeria may selectively deplete microbiota bacterial species to avoid excessive inflammation.
MPO as a Novel Susceptibility Gene in Myeloid Malignancies
Authors: Samuel Li, Ruipeng Wei, Janet Wang, Vera Adema, Teodora Kuzmanovic, Bartlomiej P. Przychodzen, Yasunobu Nagata, Cassandra M Kerr, Babal K. Jha, Francesc Sole, Torsten Haferlach, Jaroslaw P. Maciejewski, Thomas Laframboise
Journal: Blood (2019)
Comparative Effectiveness of Triplets Containing Bortezomib (V), Carfilzomib (K), or Ixazomib (I) Combined with a Lenalidomide and Dexamethasone Backbone (Rd) in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Routine Care in the United States (US)
Authors: Ajai Chari, Dorothy Romanus, Aditya Raju, Lauren Cain, Marlo Blazer, Eileen Farrelly, Dawn Marie Stull, Sikander Ailawadhi
Journal: Blood (2019)
A Rise in Plasma Coagulability during the First 3 Months Following Provoked Venous Thromboembolism Is Associated with the Development of Post-Thrombotic Syndrome in Children and Young Adults: Analysis of the Kids-DOTT Multicenter Trial-Derived Biobank
Authors: Marisol Betensky, Ernest Amankwah, Stephanie Brandal, Allen Everett, Neil A Goldenberg
Journal: Blood (2019)
Patient-Tailored Deep Sequencing of Peripheral Blood Enables Early Detection of Relapse in Childhood Acute Myeloid Leukemia
Authors: Kristian Løvvik Juul-Dam, Erik Delsing Malmberg, Anna Rehammar, Erik Kristiansson, Jonas Abrahamsson, Anni Aggerholm, Marta Maria Dirdal, Kirsi Jahnukainen, Birgitte Lausen, Hans Beier Ommen, Henrik Hasle, Linda Fogelstrand
Journal: Blood (2019)
A Phase 1b Dose Escalation Trial of Carfilzomib in Combination with Bendamustine and Rituximab in Patients with Relapsed or Refractory Non-Hodgkin Lymphoma
Authors: Swetha Kambhampati, Bita Fakhri, Weiyun Ai, Lawrence D Kaplan, Joseph Tuscano, Matthew J. Wieduwilt, Akshay Sudhindra, Jimmy Hwang, Jesika Reiner, Michelle Martinelli, Charlie Aoun, Teresa Ta, Diem Le, Michelle Padilla, Erika Crawford, Charalambos Andreadis
Journal: Blood (2019)
A Phase II Trial of Nivolumab and Ibrutinib for Patients with Relapsed or Refractory Central Nervous System Lymphoma
Authors: Jason R. Westin, Nathan H. Fowler, Loretta J. Nastoupil, Sattva S Neelapu, Hun Ju Lee, Fredrick B. Hagemeister, Maria Alma Rodriguez, Raphael E Steiner, Sairah Ahmed, Simrit Parmar, Ranjit Nair, Rebecca Harrison, Luis Fayad
Journal: Blood (2019)
Identifying Primary Immune Deficiencies in Patients with Autoimmune Cytopenias
Authors: Emma Westermann-Clark, Krisztian Csomos, Rachel Cruz Nieves, Cristina Meehan, Boglarka Ujhazi, Maryssa Ellison, Jennifer Lynne Root Mayer, Jonathan Metts, Marisol Betensky, Panida Sriaroon, Irmel Ayala, Jolan Walter
Journal: Blood (2019)