tbuckley/cabot-search huggingface dataset:
RARE-40. OUTCOMES AFTER PROTON THERAPY FOR SKULL-BASE CHORDOMA: A PROSPECTIVE STUDY
Authors: Adam Holtzman, Ronny Rotondo, Michael Rutenberg, Daniel Indelicato, Dinesh Rao, Debbie Louis, Christopher Morris, William Mendenhall
Journal: Neuro-Oncology (2019)

Abstract We evaluated treatment outcomes following definitive or adjuvant high-dose, image-guided proton therapy in 91 patients with skull-base chordoma enrolled on a prospective outcomes tracking protocol and treated between February 2007 and February 2018. The median age was 53 years (range, 22–78 years). Patients received passively scattered 3-dimensional conformal proton therapy to a median dose of 73.8 GyRBE (range, 69.6–75.6 GyRBE). Two patients received a component of intensity-modulated radiotherapy. Seventy percent (n=64) were men and 30% (n=27) were woman. Eighty-two percent (n=75) of patients had macroscopic disease at the time of radiotherapy; 18% (n=16) had undergone a macroscopic gross total resection. Overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were calculated. Proton therapy-related toxicities were scored using CTCAE v4.0. With a median follow-up of 3.7 years (range, 0.2–10 years), 26 patients experienced disease recurrence, including 26 local, 0 regional, and 1 distant recurrence. The median time to local progression was 2.2 years (range, 0.4–7.0 years). At the time of last follow-up, 66 patients were alive (56 with no evidence of disease progression) and 25 were deceased (18 with disease progression). There were no acute grade 3 toxicities related to the radiation therapy. The 4-year actuarial rates of overall survival, cause-specific survival, local control, and radiation therapy-related grade 3 toxicity-free survival were 83%, 87%, 76% and 83%, respectively. Definitive or adjuvant high-dose passively scattered 3-dimensional conformal proton therapy for skull-base chordoma provides acceptable local control, comparing favorably to historic photon data, with no acute grade ≥3 radiation-related toxicity and an acceptable rate of grade ≥3 late toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.
Response by Jia et al to Letter Regarding Article, “High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study”
Authors: Xiaoming Jia, Wensheng Sun, Ron C. Hoogeveen, Vijay Nambi, Kunihiro Matsushita, Aaron R. Folsom, Gerardo Heiss, David J. Couper, Scott D. Solomon, Eric Boerwinkle, Amil Shah, Elizabeth Selvin, James A. de Lemos, Christie M. Ballantyne
Journal: Circulation (2019)
Immune Checkpoint Inhibitor Therapy for Acute Myeloid Leukemia and Higher-Risk Myelodysplastic Syndromes: A Single-Center Experience
Authors: Rory M Shallis, Jan Philipp Bewersdorf, Lohith Gowda, Nikolai A. Podoltsev, Thomas Prebet, Steven D. Gore, Stephanie Halene, Iris Isufi, Francine M. Foss, Scott F. Huntington, Tae Kon Kim, Manoj M Pillai, Terri L Parker, Natalia Neparidze, Noffar Bar, Stuart Seropian, Amer M. Zeidan
Journal: Blood (2019)
Clonal Hematopoiesis in the Molecular Landscape of Therapy-Related Myeloid Neoplasms in Patients Previously Treated for Gynecologic and Breast Cancers
Authors: Sabine Khalife-Hachem, Khalil Saleh, Florence Pasquier, Anthony Tarabay, Cyril Quivoron, Sophie Cotteret, Christophe Willekens, Veronique Saada, Ines-Maria Vaz-Luis, Suzette Delaloge, Alexandra Leary, Hana Raslova, Filippo Rosselli, Olivier Caron, Iléana Antony-Debre, Eric Solary, Stephane de Botton, Christophe Marzac, Jean-Baptiste Micol
Journal: Blood (2019)
Megakaryocyte Colony-Forming Units (CFU-Meg) Growth Is Enhanced by Alemtuzumab Mediated Lymphocyte Depletion: In Vitro Experiments and a Case Report of Acquired Amegakaryocytic Thrombocytopenic Purpura.
Authors: Michael Doubek, Zdenek Koristek, Lenka Smardova, Jiri Mayer
Journal: Blood (2005)
IMMU-31. DRIVER GENE MUTATIONS DICTATE THE COMPOSITION OF THE IMMUNE LANDSCAPE OF GLIOBLASTOMA AND CONFER SELECTIVE RESPONSE TO IMMUNOTHERAPY
Authors: Alan Yeo, Bethany Delcuze, Laura Strauss, Vassiliki Boussiotis, Al Charest
Journal: Neuro-Oncology (2019)

Abstract The characterization of the immune landscape of glioblastoma multiforme (GBM) is rapidly emerging. Current immunotherapeutic efforts for GBM would benefit from a comprehensive and mechanistic understanding of the relationship between distinct driver gene mutations and the composition and function of the immune tumor microenvironment. The majority of GBM tumors overexpress EGFR and EGFRvIII and ~40% are mutated for PTEN. Using genetically engineered and accurate preclinical mouse models of GBM built on combinations of these driver genes, we demonstrate that the compositions of the immune landscape and the response to checkpoint blockade immunotherapy vary according to the genotype of the GBM. Mechanistically, we show that signaling networks downstream of EGFR and PTEN establish chemokine and cytokine profiles that parallel the levels of intra-tumoral polymorphonuclear myeloid-derived suppressor cells and regulatory T cells. Additionally, tumor-associated microglia/macrophages number, function and polarization are heavily influenced by specific driver-gene mutation combinations. Furthermore, we demonstrate that efficacy of checkpoint blockade therapy using anti PD-1 as a single agent or in combination with anti CTLA-4 is dependent on EGFR and PTEN status. Taken together, our findings demonstrate that important components of the tumor immune microenvironment are influenced by specific driver gene mutations. Our results suggest that stratifying patients based on tumor genotype or signaling events may be informative for selection of appropriate candidates for checkpoint blockade therapy and present an opportunity to pharmacologically modulate GBM signaling with targeted therapeutics to sensitize patients to immunotherapy.
Life or Death by EEG
Authors: E. Charles Kunkle
Journal: JAMA (1965)

To the Editor:—  A communication by Dr. Hannibal Hamlin in the Oct 12, 1964, issue ofThe Journal( 190 :112) succinctly describes the value of the EEG as an index of the point of  return in the moribund patient. He suggests that in most patients an isoelectric record justifies giving up further efforts at artificial maintenance of respiratory and heart action.  Of the accessory criteria which he offers, one seems unreasonable, at least in its stated form; he urges that, in addition to the recording of the EEG, the physician should demonstrate that the patient has no spontaneous respiration for a minimum of 60 minutes. Since spontaneous breathing may sometimes alter in rhythm to occur in synchrony with a respirator and thereby be masked by it, conclusive proof that the patient cannot breathe at all on his own presumably requires withholding mechanical aids for the prolonged period mentioned. This
Can Peri-Transplant Radiation Therapy Improve Outcomes of Autologous Stem Cell Transplant in Hodgkin Lymphoma?
Authors: Harsh Shah, Paramveer Singh, Jorgena Kosti, Hyejeong Jang, Seongho Kim, Andrew Kin, Asif Alavi, Lois Ayash, Voravit Ratanatharathorn, Joseph P. Uberti, Abhinav Deol
Journal: Blood (2019)
Yeast-based immunotherapy and the threshold of EGFR expression for immune recognition against glioma overexpressing self-antigen
Authors: Yingnian Lu, Don Bellgrau, Timothy C. Rodell, Alex Franzusoff
Journal: Cancer Research (2006)

1405  The administration of Tarmogens™, which are whole, heat-inactivated Saccharomyces cerevisiae yeast containing defined quantities of target antigens, elicit T cell-mediated immune responses that recognize and ablate antigen-bearing tumors. Yeast are avidly taken up via pattern recognition receptors, such as glucan, mannan and Toll-like receptors (TLRs) on antigen-presenting dendritic cells (DCs), initiating an innate immune response. This innate immune response drives DC maturation and secretion of pro-inflammatory cytokines, followed by the MHC-mediated presentation of yeast-expressed tumor antigens to initiate antigen-associated adaptive responses. Yeast may be administered repeatedly without the generation of neutralizing host anti-yeast antibodies, thus boosting tumor antigen-specific immune responses against over-expressed self or mutated tumor antigens. We previously described that Tarmogens delivering mutated Ras proteins elicited therapeutic protection against carcinogen-induced mutant Ras-expressing lung tumors in mice (Cancer Res 64: 5084). A Phase 1 trial treating colorectal and pancreas cancer patients with the mutant Ras-expressing Tarmogens demonstrated the safety and immunogenicity of this approach. In the present studies, yeast delivering human or rat EGFR as the tumor antigen (GI-3000 Tarmogens) were tested as immunotherapeutics against intracranial rat glioma challenge. Intranasal administration of GI-3000 expressing either rat or human EGFR proteins resulted in antigen-specific protection against intracranial challenge with 9L glioma transfected with non-mutated rat or human EGFR in Fischer rats. The immune-mediated tumor ablation was dependent on EGFR overexpression, as demonstrated by flow cytometry of tumor cells isolated and analyzed from responding and non-responding animals. The profile of cell surface EGFR density revealed an antigen threshold below which tumor cells were not recognized by cell-mediated immune responses. The apparent requirement for EGFR overexpression in immune-mediated protection may explain the absence of grossly observable off-target effects in tissues with normal levels of EGFR expression. These preclinical data indicate that Tarmogen administration is capable of breaking tolerance to overexpressed self antigens, supporting clinical evaluation in relevant cancer indications such as EGFR-overexpressing glioblastomas.
Disease Risk Comorbidity Index for Patients Receiving Haploidentical Allogeneic Hematopoietic Transplantation
Authors: Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Sining Liu, Kaiyan Liu, Xiaojun Huang
Journal: Blood (2019)
Electrostatic complementarity of B-cell receptor CDR3s and TP53-mutant amino acids in breast cancer is associated with increased disease-free survival rates
Authors: Juan F. Arturo, Boris I. Chobrutskiy, Michelle Yeagley, Dhruv N. Patel, Shayan Falasiri, Jay S. Patel, George Blanck
Journal: Cellular and Molecular Immunology (2019)
Outcomes in Adolescent and Young Adult (AYA) Acute Lymphoblastic Leukemia (ALL): A Report from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC)
Authors: Prasanth Ganesan, Hasmukh Jain, Bhausaheb Bagal, Papagudi Ganesan Subramanian, Biju George, Anu Korula, Nikita Mehra, Kiran Kumar Satti, Dinesh Bhurani, Rayaz Ahmed, Maitreyee Bhattacharyya, Smita Kayal, Jina Bhattacharyya, Uday Yanamandra, Suman Kumar, Chepsy C Philip, Ambily Nadaraj, Om Prakash, Jeyaseelan Lakshmanan, Vikram Mathews, Manju Sengar
Journal: Blood (2019)
Vaso-Occlusive Crises and Costs of Sickle Cell Disease from a Commercial Payer's Perspective
Authors: George J Joseph, Dominick Latremouille-Viau, Vikash Kumar Sharma, Patrick Gagnon-Sanschagrin, Menaka Bhor, Ankur Khare, Mukesh Kumar Singh, Elizabeth Serra, Mikhail Davidson, Annie Guerin, Nirmish Shah
Journal: Blood (2019)
Interval Exercise Training (IET) Is Feasible and May Improve Cardiorespiratory Performance Prior to Hematopoietic Cell Transplantation
Authors: Mathew Meeneghan, Anna Snavely, Abbie Smith-Ryan, Claudio L Battaglini, Bryce B Reeve, Ethan Basch, Antonia Bennett, Charlotte Shatten, Brett Phillips, Jonathan Serody, Don A. Gabriel, Katarzyna Joanna Jamieson, James Coghill, Paul M. Armistead, Thomas C. Shea, William A. Wood
Journal: Blood (2014)
Antibiotic consumption in Belgian acute care hospitals: analysis of the surveillance methodology, consumption evolution 2003 to 2016 and future perspectives
Authors: Eline Vandael, Koen Magerman, Samuel Coenen, Herman Goossens, Boudewijn Catry
Journal: Eurosurveillance (2019)

BackgroundStudies have demonstrated the link between antimicrobial consumption and the development of antimicrobial resistance. Surveillance of antimicrobial consumption is an action point of the European Commission's 'One Health Action Plan Against Antimicrobial Resistance'.AimThis study aims to compare two methodologies for antibiotic consumption surveillance, investigate the 14-year evolution of antibiotic consumption in Belgian acute care hospitals and discuss future perspectives.MethodsWe compared self-reported data (old methodology) and reimbursement data (new methodology) of national antibiotic consumption surveillance in hospitals. Descriptive analyses were performed on the reimbursement data collected per year and per trimester (2003-2016), per hospital and per unit. Antibiotic consumption was compared with European Surveillance of Antimicrobial Consumption Network (ESAC-Net) results.ResultsThe median differences for defined daily doses (DDDs)/1,000 patient days and DDDs/1,000 admissions were 3.09% and 3.94% when comparing the old vs new methodology. Based on reimbursement data, the median antibiotic consumption in 2016 in 102 Belgian acute care hospitals was 577.1 DDDs/1,000 patient days and 3,890.3 DDDs/1,000 admissions with high variation between hospitals (interquartile ranges (IQR): 511.3-655.0 and 3,450.0-4,400.5, respectively), and similar to 2015. Based on DDDs/1,000 patient days, the magnitude of consumption is comparable with the Netherlands, Denmark and Sweden, but is higher when based on DDDs/1,000 admissions.ConclusionAntibiotic consumption in Belgian acute care hospitals has remained overall stable over time. However, the high variation across hospitals should be further investigated. This surveillance data could be used for benchmarking and assessing interventions to improve antibiotic consumption in these hospitals.
Hypertension in Pregnancy
Authors: Benjamin Tenney
Journal: New England Journal of Medicine (1953)

IN discussions of hypertension in pregnancy the term "toxemias of pregnancy" has been discarded. Pre-eclamptic toxemia is the only potentially toxic syndrome, and even that has not been established. Hypertensive disease in pregnancy is classified in three groups, as follows: essential hypertension (patients with pre-existing vascular disease); renal disease (patients with pre-existing renal disease, with or without hypertension); and pre-eclamptic toxemia and eclampsia. It is believed that a superimposed pre-eclamptic toxemia is likely to occur in the first two groups. It is difficult to prove the development of a superimposed lesion on a pre-existing one, but because the early effects . . .
Efficacy of Targeted Therapy in Novel Pre-Clinical in Vitro and In Vivo Models of Richter Transformation-Diffuse Large B-Cell Lymphoma (RT-DLBCL)
Authors: Vrajesh Karkhanis, Warren Fiskus, Christopher Peter Mill, Abhishek Maiti, Bernardo H Lara, James V Maher, Isean Bhalla, Nancy Shao, Michael R Green, Joseph D. Khoury, Kapil N. Bhalla
Journal: Blood (2019)
Results of the Phase 3 VITAL Study of NEOD001 (Birtamimab) Plus Standard of Care in Patients with Light Chain (AL) Amyloidosis Suggest Survival Benefit for Mayo Stage IV Patients
Authors: Morie A Gertz, Adam D. Cohen, Raymond L Comenzo, Charles Du Mond, Eftathios Kastritis, Heather J Landau, Edward N. Libby, Michaela Liedtke, Giampaolo Merlini, Vaishali Sanchorawala, Stefan O. Schönland, Ashutosh D Wechalekar, Jeffrey A. Zonder, Gene Kinney
Journal: Blood (2019)
Successful Bone Marrow Transplantation Using an Immunomyelosuppressive Conditioning in Patients with Severe Congenital Neutropenia: The Results of a Single-Institute
Authors: Risa Matsumura, Shiho Nishimura, Yoko Mizoguchi, Mizuka Miki, Maki Taniguchi, Maiko Shimomura, Shuhei Karakawa, Shinji Mochizuki, Takehiko Doi, Hiroshi Kawaguchi, Masao Kobayashi
Journal: Blood (2019)
Is the Achievement of Pre-Autologous Transplant CR Necessary Indeed in Refractory/ Relapsed DLBCL Patients? a Retrospective Multicenter Study
Authors: Liat Shargian-Alon, Hanna Bernstine, Galit Perets, Ronit Gurion, Anat Gafter-Gvili, Oren Pasvolsky, Michal Navon Sela, Chava Perry, Irit Avivi, Odelia Amit, Pia Raanani, Ron Ram, Moshe Yeshurun
Journal: Blood (2019)
Molecular MRD Monitoring Is Feasible in the Majority of Children with AML and Is Highly Predictive of Outcome: Results from the International MyeChild01 Study
Authors: Jelena Jovanovic, Nicola Potter, Anju Kanda, Claire Schwab, Aimee E Jackson, Richard Dillon, Anna Lawson, Manohursingh Runglall, Paresh Vyas, Paul Virgo, Geoff Shenton, Nicholas Heaney, Beki James, Katharine Patrick, Persis J Amrolia, Jean-Hugues Dalle, Gerard Michel, Andrew S. Moore, Hélène Lapillonne, Claude Preudhomme, Guy Leverger, Owen P Smith, Andre Baruchel, Yves Bertrand, Arnaud Petit, Keith Wheatley, Pamela R. Kearns, Christine J. Harrison, Brenda Gibson
Journal: Blood (2019)
Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People
Authors: Samyah Shadid, Kessewa Abosi-Appeadu, Anne-Sophie De Maertelaere, Justine Defreyne, Laurens Veldeman, Jens J. Holst, Bruno Lapauw, Tina Vilsbøll, Guy T’Sjoen
Journal: Diabetes Care (2019)

OBJECTIVE The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study. RESEARCH DESIGN AND METHODS Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated. RESULTS In TM, body weight (2.8 ± 1.0 kg; P &amp;lt; 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P &amp;lt; 0.01), and waist-to-hip ratio (−0.03 ± 0.01; P &amp;lt; 0.01) increased. Fasting insulin (−1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (−1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (−1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (−0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] × min; P &amp;lt; 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] × min; P &amp;lt; 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (−2.3 ± 0.4 kg; P &amp;lt; 0.01) and waist-to-hip ratio (−0.03 ± 0.01; P &amp;lt; 0.01). Insulin (3.4 ± 0.8 mU/L; P &amp;lt; 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P &amp;lt; 0.01) rose, fasting GIP (−1.4 ± 0.8 pmol/L; P &amp;lt; 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] × min; P &amp;lt; 0.01), but fasting glucose (−0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] × min) remained unchanged. CONCLUSIONS In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.
RTHP-31. EMERGENCY RADIOTHERAPY IN INTRACRANIAL GERM CELL TUMORS (GCTS) PATIENTS WITH KPS≤ 40: ARETROSPECTIVE ANALYSIS OF 27 CASES
Authors: Linbo Cai, Mingyao Lai, Juan Li, Cheng Zhou, Qingjun Hu, Zhaoming Zhou
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES To evaluate the potential role of emergency radiotherapy in intracranial germ cell tumors GCTs) patients with KPS ≤ 40. METHODS A total of 27 primary intracranial germ cell tumors (GCTs) patients with KPS ≤ 40 between Jan 2007 and Dec 2018 were retrospectively evaluated. The median age at initial diagnosis was 15 years (range, 528 years). Among those, 11 patients were germinoma and 16 patients were nonseminomatous germ-cell tumors (NGGCTs). There were 9 solitary pineal, 5 suprasellar, 3 basal ganglia and 10 multifocal and disseminated tumors. All patients received emergency radiotherapy (2 Gy/fx/d). Prior to radiotherapy, 11 patients were manifested with hydrocephalus, 10 with hypopituitarism and 5 with intracranial tumo apoplexy. RESULTS The average follow up time was 44.4 months. The 5 year progression free survival rate and overall survival rate were 29.6% and 33.3%. The median overall survival time was 38 months. In particular, the median intracranial hypertension symptoms relief time was 2 days. The median KPS following radiotherapy was 80 comparing to 30 prior to radiotherapy (P &lt; 0.05). A significant improvement on KPS of 46.7±27.3 was observed in this study. CONCLUSION Emergency radiotherapy is implicated as a promising intervention for GCTs patients with elevated intracranial pressure (ICP). These advantages can be interpreted as direct cell killing effect and fast tumor shrinkage by ionizing radiation. However, to substantiate our findings, further investigations were highly warranted.
QOLP-30. CLINICAL PREDICTIVE MODEL FOR THE DEVELOPMENT OF VENOUS THROMBOEMBOLISM IN GLIOBLASTOMA
Authors: Shlomit Yust-Katz, Vijaya Donthireddy, Jacob Mandel, Hussna Abunafeesa, Neha Patil, Dhiraj Yadav, Hiba Jabbour-Aida, Jimin Wu, Ying Yuan, Spiridon Tsavachidis, Tobias Walbert, Melissa Bondy, Terri Armstrong
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The risk of venous thromboembolism (VTE) remains high for patients with glioblastoma (GBM) throughout the disease trajectory. Our previous work demonstrated the Khorana scale lacks specificity in this population. We therefore constructed, and attempted to validate a predictive model specific for the development of VTE during adjuvant chemotherapy in glioblastoma patients. METHODS A prior study of GBM patients treated at MD Anderson (MDACC) during the years 2005–2011 found from a multivariate analysis that male sex, BMI ≥ 35, KPS ≤ 80, and steroid therapy were significantly associated with the development of VTE. A predictive model from the MDACC cohort was created using these risk factors, and we attempted to validate the model in an independent cohort of GBM patients treated at Henry Ford from 2010–2015. RESULTS To develop the model 315 patients from the MDACC cohort were randomly divided into two parts: training (75% of data) used for model building, and validation (25% of data) used for model validation. Using the predictive model, the MDACC validation cohort found 80% sensitivity and 80% specificity. We then validated the model in the Henry Ford cohort of 190 GBM patients of which 50 developed a VTE. In the external validation set, the predictive model was found to have a sensitivity = 78% and specificity = 49.3% (Fisher test p-value = 0.0008). CONCLUSIONS Our predictive model for the development of VTE during adjuvant chemotherapy in GBM patients retained high sensitivity in an external data set, however high specificity was lost. While the specificity in our model was higher than in previous studies examining the Khorona scale in GBM patients, further refinement to improve the models reliability to correctly identify people who will not later develop a VTE may be helpful.