tbuckley/cabot-search huggingface dataset:
EXTH-40. SPECIFIC DENDRIMER-MEDIATED DELIVERY OF IMMUNOTHERAPY BLZ945 TO TUMOR-ASSOCIATED MACROPHAGES IMPROVES THERAPEUTIC EFFICACY IN GLIOBLASTOMA
Authors: Kevin Liaw, Rajsekhar Reddy, Rishi Sharma, Sebastian Salazar, Ambar Jinemez, Sujatha Kannan, Rangaramanujam Kannan
Journal: Neuro-Oncology (2019)

Abstract Patients with glioblastoma have failed to see improved outcomes despite the discovery of powerful anti-cancer drugs because such therapies do not adequately cross the blood-brain barrier and penetrate into solid tumors to access pathological cells. In addition to these delivery challenges, tumors polarize host macrophages into tumor-associated macrophages (TAMs), which suppress the tumor-killing response and create a growth-conducive immune environment for cancer cells. As a result, TAMs are promising therapeutic targets but translational efforts targeting them have largely failed due to low response rates and high systemic toxicities. Therefore, a vehicle that carries immunotherapies into the brain, deep into solid tumors, and specifically to TAMs while remaining inactive in the body provides a promising clinical strategy. Here, we present hydroxyl-terminated polyamidoamine (PAMAM) dendrimers as novel targeted drug delivery systems to overcome these delivery challenges in the GL261 mouse model of glioblastoma. Upon systemic administration, these dendrimers, without any targeting ligands, are able to cross the blood-brain barrier, distribute uniformly throughout the solid glioblastoma tumor, and localize specifically within TAMs. Dendrimers display high tumor specificity (&gt;5-fold compared to the contralateral hemisphere) and minimal systemic accumulation (&lt; 5% initial dose remaining in livers or kidneys after 24 hours). We then conjugated BLZ945, a potent immunotherapy that prevents tumors from recruiting TAMs, to the dendrimer via pH-sensitive linkers for triggered intratumoral and intracellular release. We find that a single systemic dose of dendrimer-delivered BLZ945 halfway through disease progression prolongs survival by &gt;30% compared to free BLZ945 and untreated cohorts. These survival benefits were accompanied by amelioration of disease progression and improved motor function. Finally, we demonstrate that repeat dosing of dendrimer-delivery BLZ945 in combination with current standard of care temozolomide provides robust, synergistic improvements to survival and disease severity. These studies validate the potential of dendrimers for localized immune manipulation in glioblastoma.
Complementary Transplantation with Unrelated Cord Blood Following Haploidentical Stem Cells for Juvenile Myelomonocytic Leukemia:Double-Centers Study from China
Authors: Zhiyong Peng, Xiaoqin Feng, Huaying Liu, Jianyun Liao, Chaoke Bu, Yuelin He, Jianmin Zhang, Jingyu Gao, Chunfu Li
Journal: Blood (2019)
SURG-24. A RISK SCORE FOR PREDICTING DEVELOPMENT OF DIABETES INSIPIDUS AFTER PITUITARY ADENOMA RESECTION
Authors: Christina Jackson, Chau Vo, Marcus Daniels, Kaisorn Chaichana
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The development of diabetes insipidus (DI) after pituitary adenoma resection is associated with worse post-surgical morbidity and longer hospital stay. Identification of clinical predictors of development of DI would allow for appropriate stratification of patients to optimize preoperative counseling and postoperative management. METHODS We conducted a retrospective review of 349 patients who underwent pituitary adenoma resection at Johns Hopkins Hospital between 2003 and 2017. We used unadjusted and adjusted logistic regression to identify predictors of developing DI. Factors which were associated with DI development (p&lt; 0.1), were included in our multivariable model. Factors which remained associated with DI development were then used to develop a DI risk score. RESULT: 67 (19.2%) patients developed post-surgical DI. Patients who had symptoms of prolactinoma, surgery through one nare, or were on steroid treatment were more likely to develop DI. Conversely, patients who had unilateral cavernous sinus invasion were less likely to develop DI. We used these predictors to generate the DI risk score. Patients were assigned 1 point for each risk factor (symptoms of prolactinoma, steroids, or surgery through one nare) for developing DI, but 1 point was subtracted if they had a protective factor (unilateral cavernous sinus invasion). Patients with 0 points had a 10.7% probability of developing DI, patients with 1 point had a 18.5% probability of developing DI, patients with 2 points had a 41.2% probability of developing DI, and patients with 3 points had a 44.4% probability of DI. CONCLUSIONS We identified several predictors of DI development after pituitary adenoma resection, and used these to generate a DI risk score. The DI risk score could help stratify patients’ likelihood of postsurgical DI development, although validation through larger prospective multi-center studies are needed.
RARE-06. A CASE OF RECURRENT SUPRATENTORIAL EXTRAVENTRICULAR ANAPLASTIC EPENDYMOMA IN ADULT
Authors: Dong-Gee Kang, Ho-Jun Kang
Journal: Neuro-Oncology (2019)

Abstract Supratentorial extraventricular anaplastic ependymoma (SEAE) in adults is a relatively rare intracranial tumor. Because of very low prevalence, SEAE has been reported only a few cases. According to a recent study, SEAE is associated with a poor prognosis and there is no definite consensus of optimal treatment. We report a case of an adult SEAE patient who had no recurrence until seven years after gross total resection(GTR) followed by conventional radiotherapy. A 42- year- old male had a persistent mild headache, left facial palsy, and dysarthria. Preoperative neuroimaging revealed an anaplastic astrocytoma or supratentorial ependymoma in the right frontal lobe. A GTR was performed, followed by adjuvant radiotherapy. Histologic and immunohistochemical results revealed anaplastic ependymoma, After seven years of initial therapy, a regular follow-up MRI showed a 3-cm –sized partially cystic mass in the same area as the initial tumor. The patient underwent a craniotomy, and a GTR was performed. Histopathologic examination revealed recurrence of the SEAE. External radiotherapy was performed. The patient has been stable without any disease progression or complications for 12 months since the surgery for recurrent SEAE
Clinical Characteristics and Cardioavscular Events in Patients with Esential Thrombocythemia with &lt;10% Vs. ≥10% JAK2 V617F Allele Burden
Authors: Blanca Xicoy, Natalia Estrada, Alberto Alvarez-Larran, Xavier Calvo Gonzalez, Beatriz Bellosillo, Arenillas Leonor, Iván Martín, Juan Carlos Hernandez Boluda, Vicente Vicente, Andrea Espasa, Francisca Ferrer Marin, Gonzalo Caballero, Valle Recanses Flores, María Teresa Gómez-Casares, Marisol Xandri, Beatriz Cuevas, Jose Maria Alonso Alonso, Manuel Pérez, Maribel Mata, Venancio Conesa, Carmen Albo, Victor Marco, Juan-Manuel Alonso, Maria Laura Fox, Raul Perez, M Jesús Rodriguez Domínguez, Valentin Garcia Gutierrez, Marina Gordillo, Maria DOLORES Carrera, Esperanza Such, Carlos Fernández, Lurdes Zamora
Journal: Blood (2019)
Unsupervised Clustering of DNA Copy Number Profiles Identifies a High-Risk Subtype of Hyperdiploid Multiple Myeloma: An Mmrf Commpass Analysis
Authors: Austin Christofferson, Sheri Skerget, Jessica Aldrich, Christophe Legendre, Sara Nasser, Jennifer Yesil, Daniel Auclair, The MMRF CoMMpass Network, Sagar Lonial, Jonathan J Keats
Journal: Blood (2019)
CMET-17. RENAL CELL CARCINOMA BRAIN METASTASES TREATED WITH STEREOTACTIC RADIATION THERAPY AND NIVOLUMAB DOES NOT ALTER LESIONAL OR CLINICAL OUTCOMES
Authors: Homan Mohammadi, Aaron Tolpin, Nicholas Figura, Jeffrey Peacock, Daniel Oliver, Austin Sim, Russel Palm, Kamran Ahmed, James Liu, Nam Tran, Arnold Etame, Michael Vogelbaum, Timothy Robinson, Michael Yu
Journal: Neuro-Oncology (2019)

Abstract Metastases (BM) carries the risk of hemorrhaging lesions and can be effectively treated using stereotactic radiotherapy (SRT). Nivolumab is a recently approved immunotherapy for stage IV RCC. We evaluate whether patients with RCC BM treated with SRT overlapping with nivolumab have altered clinical and BM outcomes. METHODS: 38 consecutive patients were identified in our retrospective database from 1/2011 to 6/2018. Analyses were performed on a per-lesional basis (n=170), per-treatment session basis (n=79), and per-patient basis (n=38). Patients who received nivolumab within 6 months of SRT were considered to have overlapping treatments. ROC curve, chi-squared, Kaplan-Meier, log-rank, and Cox regression model were employed for statistical analyses. RESULTS: A total of 7 (18.4%) patients received overlapping treatments for 64 (37.6%) eligible lesions. Median follow-up was 15.4 months and median overall survival from first BM treatment was 14.8 months (0.5 – 98.4). Median time to subsequent distant brain and non-brain failures were 3.4 and 2.2 months, respectively. Median time to local failure was 20.2 months (two lesions). There were 11 hemorrhagic toxicities (7 in the nivolumab group) and 17 radionecrosis toxicities (4 in the nivolumab group) with no significant difference amongst the groups. Lesions receiving nivolumab within 6 months of SRT did not exhibit a higher rate of toxicity (p=0.521) but had a shortened time to hemorrhage (p&lt; 0.001). Patients who received SRT &gt; 1 month after nivolumab had a prolonged time to subsequent distant brain failure (median 11.1 months) than patients who received SRT &gt; 1 month before (median 3.1 months) or within 1 month (median 1.6 months) of nivolumab, p=0.014. CONCLUSIONS: Overlapping nivolumab with SRT is safe with no increased risk of hemorrhagic lesions. An optimal treatment sequence of nivolumab administration followed by SRT prolongs the time to subsequent BM and warrants further investigation.
Azacytidine Inhibits Megakaryopoiesis Via the Induction of Immunogenic RNA Species and Activation of Type-I Interferon Signaling
Authors: Ujunwa Cynthia Okoye-Okafor, Komal Kumar Javarappa, Dimitrios Tsallos, Joseph J Saad, Lumie Benard, Victor Thiruthuvanathan, Sally Cole, Madhuri Tatiparthy, Stephen Ruiz, Stefanie DeFronzo, Celine Pallaud, Pedro Marques Ramos, Amit Verma, Aditi Shastri, Caroline A Heckman, Britta Will
Journal: Blood (2019)
Penicillin for Infected Hands
Authors: A. G. Dingley
Journal: BMJ (1947)

BMICAsH 88ORThe reduced glutathione level in the blood rises after a single injection of 20,000 i.u. of penicillin and becomes constantly higher during prolonged treatment.This fact may be of im- portance to the mode of action of penicillin, glutathione being composed of glutamic acid, cysteine, and glycocoll (glycine).It is possible, therefore, that this increased amount of glutathione has a similar effect upon the glutamic acid of bacteria, as sul- phonamides have against para-aminobenzoic acid.Detailed communications in connexion with this work appeared or will be published in the Orvosok Lapja and Magyar
The Number of Organ Failures, but Not Graft-Versus-Host Disease, Determines Outcome of Allogeneic Stem Cell Transplantation Recipients Requiring Intensive Care
Authors: Corentin Orvain, Francois Beloncle, Sylvain Thepot, Achille Kouatchet, Sylvie Francois, Philippe Guardiola, Anne Corby, Pierre Asfar, Mathilde Hunault-Berger, Norbert Ifrah, Aline Tanguy-Schmidt
Journal: Blood (2014)
Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Stephen A Harrison, Mustafa R Bashir, Cynthia D Guy, Rong Zhou, Cynthia A Moylan, Juan P Frias, Naim Alkhouri, Meena B Bansal, Seth Baum, Brent A Neuschwander-Tetri, Rebecca Taub, Sam E Moussa
Journal: The Lancet (2019)
TMOD-20. COMBINING TARGETED INHIBITOR AND RADIOTHERAPY IN TREATING ANAPLASTIC MENINGIOMA
Authors: Yufen Wang, Craig Horbinski, Charles James, Vythialingam Sathiaseelan, John Kalapurakal
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Anaplastic meningiomas pose a serious health concern due to their propensity for recurrence and brain invasion. Five-year overall survival of patients with anaplastic meningiomas is less than 10%, similar to that of glioblastoma patients. Standard treatment of recurrent anaplastic meningioma is radiotherapy (RT), but radioresistance is common. New therapeutic strategies, used singularly or in combination with RT, are urgently needed. Since deletion of the gene encoding the p16 cell cycle checkpoint protein is common in anaplastic meningioma, we hypothesized that such tumors would be sensitive to Palbociclib, a cdk4/6 inhibitor, and that Palbociclib could enhance RT efficacy. METHODS CH157 anaplastic meningioma cells were used in vitro for investigating tumor cell proliferation response to RT and Palbociclib, either alone or in combination, and as indicated by MTT assay results. CH157 cells were also used to establish intracranial xenografts in mice treated with RT or Palbociclib. Accuracy of RT dose was verified with calibrated MOSFET\OSLD dosimeters. Mice were monitored for intracranial tumor growth and response to treatment, as indicated by bioluminescence imaging. Length of survival data was collected and analyzed by log-rank test. RESULTS At two days post RT, the in vitro anti-proliferative effect of 2, 6, and 10 Gy radiation was significantly enhanced with concurrent 1mM Palbociclib (p &lt; 0.001). Daily administration of Palbociclib (150 mg/kg) for 1 week significantly extended the survival of mice with intracranial CH157 xenografts (group mean value of 18.4 vs. 13.6 days with vehicle control, p &lt; 0.001). A single dose of 10 Gy RT was superior to 6 Gy administered 1x and 2Gy/day administered on 5 consecutive days (group mean values of 37.4 vs. 24.0 vs. 24.6, respectively: p &lt; 0.001). CONCLUSIONS These data support further investigation of RT + Palbociclib for treating p16-deficient anaplastic meningiomas.
Laevadosin in Muscular Dystorphy
Authors: J. Jacobs
Journal: BMJ (1965)

American surgeon and his family on three months' " holiday."Although he worked as hard as the rest of us, he thoroughly enjoyed the change of surroundings and the stimulus of new problems which he found, and he insisted that it was worth every dollar he had spent.When he worked out the cost, he discovered that it was equivalent to the price of a new Cadillac.I doubt if it can always be done for that price, but if we can persuade some British doctors to do likewise their contribution towards meeting Africa's need would be worth incalculably more than the cost of a new Rolls.Those of us working in Africa are constantly aware of the danger of our medicine becoming rusty.This has to be balanced against what we are actually achieving.It seems precious little at times in the chaos of trying to be all things to all patients.These things cannot be measured in academic terms, but short-term working visits by sympathetic doctors from "overdeveloped " countries would do a great deal to revive our drooping spirits and keep alight the flickering academic light.Just to have someone with whom to talk shop means more than will be appreciated by those plagued with a surfeit of medical meetings.-Iam, etc.,
Randomized Open-Labeled Academic Trial Comparing Standard AZA Therapy with Combination of G-CSF with AZA in High Risk MDS Patients - Interim Analysis
Authors: Anna Jonasova, Lubomir Minarik, Vojtech Kulvait, Michal Pesta, Adel Schaffartzikova, Galina Kislik, Nina Dusilkova, Zuzana Zemanova, Tomas Stopka
Journal: Blood (2019)
Allogeneic Hematopoietic Cell Transplantation May Improve Long-Term Outcomes in Patients with Ph-like Acute Lymphoblastic Leukemia with CRLF2 Overexpression
Authors: Paul Koller, Rima M. Saliba, Celina Ledesma, Gabriela Rondon, Uday Popat, Amin M. Alousi, Rohtesh S. Mehta, Betul Oran, Amanda L. Olson, Chitra Hosing, Muzaffar H. Qazilbash, Issa F. Khouri, Stefan O. Ciurea, Elizabeth J. Shpall, Jeffrey L. Jorgensen, Sa A Wang, Nitin Jain, Elias Jabbour, Hagop M. Kantarjian, Richard E Champlin, Marina Y Konopleva, Partow Kebriaei
Journal: Blood (2019)
Transplanted Vasoactive Intestinal Peptide-Secreting Donor Plasmacytoid Dendritic Cells Migrate to Lymphoid Organs and GvHD Target Organs
Authors: Jingru Zhu, Yitong Wang, Jingxia Li, Yiwen Li, Alina Ulezko Antonova, Cynthia R. Giver, Jianming Li, Shuhua Wang, Edmund K. Waller
Journal: Blood (2019)
Spectrum of Abnormalities and Clonal Transformation in Germline RUNX1 Familial Platelet Disorder and a Comparative Analysis with Somatic RUNX1 Mutations in Myeloid Neoplasms
Authors: Emma Difilippo, Giacomo Coltro, Ryan M. Carr, Abhishek A Mangaonkar, Moritz Binder, Shakila P Khan, Vilmarie Rodriguez, Naseema Gangat, Alexandra Wolanskyj, Rajiv K. Pruthi, Dong Chen, Rong He, David S Viswanatha, Terra Lasho, Christy Finke, Ayalew Tefferi, Animesh Pardanani, Mark Litzow, Mrinal M Patnaik
Journal: Blood (2019)
Need for Multidisciplinary Research and Data-Driven Guidelines for the Cardiovascular Care of Patients With Cancer
Authors: Wouter C. Meijers, Javid J. Moslehi
Journal: JAMA (2019)

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NIMG-54. DIFFUSION MRI PHENOTYPES PREDICT OVERALL SURVIVAL BENEFIT FROM BEVACIZUMAB IN RECURRENT GLIOBLASTOMA WITH A LARGE TUMOR BURDEN: EVIDENCE FROM CLINICAL PRACTICE AND A MULTICENTER PHASE 3 TRIAL
Authors: Kunal Patel, Catalina Raymond, Jingwen Yao, Joseph Tsung, Jodi Goldman, Jacob Schlossman, Caleb Tran, Andrew Brenner, Nicholas Butowski, Patrick Wen, Whitney Pope, Matthew Ji, Albert Lai, P Leia Nghiemphu, Tamar Rachmilewitz Minei, Yael Cohen, Dror Harats, Timothy Cloughesy, Benjamin Ellingson
Journal: Neuro-Oncology (2019)

Abstract We have previously shown that diffusion MR characteristics are a predictive imaging biomarker for survival benefit in recurrent glioblastoma treated with anti-VEGF therapy; however, contemporary clinical use of bevacizumab is often limited to patients with very large tumors and/or after multiple recurrences. We hypothesize that diffusion MR characteristics can be used to predict long-term survival benefit in these patients, which may be beneficial for clinical decision-making. The current study identified 83 recurrent glioblastoma patients from our institution who were treated with bevacizumab over the past 5 years with high quality anatomic and diffusion MRI data. Of these 83 patients, 35 had large contrast enhancing tumors (&gt;20cc or &gt;3.4cm diameter, group average). Additionally, we identified 37 recurrent glioblastoma patients from the bevacizumab treated control arm of a recent multicenter phase III trial (NCT02511405) with high quality data and large enhancing tumors for validation. Pre-treatment tumor volume was quantified using T1 subtraction maps and apparent diffusion coefficient (ADC) histogram analysis was used to phenotype patients as having high (&gt; 1.24 um2/ms) or low (&lt; 1.24 um2/ms) ADCL, the mean value of the lower peak using a double Gaussian mixed model. Median overall survival in patients with large volume recurrent glioblastoma was ~5.7 months. High ADCL was associated with significantly longer overall survival (OS) compared with low ADCL in both single center (P=0.0271, HR=0.486, mOS=5.5 vs. 2.8mo) and multicenter phase III data (P=0.0457, HR=0.507, mOS=7.9 vs. 5.7mo). Accounting for absolute tumor volume and age, both cohorts showed that ADCL was an independent prognostic factor for OS (Cox, P&lt; 0.01). In summary, pre-treatment diffusion MR imaging is an independent predictive biomarker for OS in recurrent glioblastoma with a large tumor burden.
Improvement in Quality of Life Outcomes and Bleeding Rates among Patients Switching from On-demand FVIII to Prophylactic BAY 94-9027 in the PROTECT VIII Study
Authors: Jonathan M. Ducore, Shadan Lalezari, Elena Santagostino, Sanjay P Ahuja, Monika Maas Enriquez, Claudia Tueckmantel, Mark Reding
Journal: Blood (2019)
Impact of Osseous and Non-Osseous Extramedullary Disease in Multiple Myeloma: Clinical Characteristics and Outcomes in a Latin American Population
Authors: Cesar Vargas-Serafin, Aldo A Acosta-Medina, Juan Rangel-Patiño, Daniela Perez-Samano, Deborah M. Martinez-Banos, Christianne Bourlon
Journal: Blood (2019)
A Case of Conjoined Twins
Authors: W. Stiggelbout
Journal: BMJ (1958)

DINITROPHENOL AND DIABETES MELLITUSBDIgANSRNAL 727sugar and glycosuria, though for the same order of increase in oxygen consumption the effect of D.N.P. is slight com- pared with that of aspirin, and would in itself have no prac- tical value in the treatment of the disease.This raises the question, Is it enough to say that the fundamental action of both D.N.P. and salicylate is inhibition of oxida- tive phosphorylation without further specification to account for quantitative differences ?Summary Salicylate and 2: 4-dinitrophenol (D.N.P.) inhibit oxidative phosphorylation.Salicylate also controls moderately severe diabetes mellitus.The effect of D.N.P. in the disease has been investigated.Increased oxygen -consumption from D.N.P. of the same order as is required with aspirin to control moder- ately severe diabetes lowered fasting blood sugar and glycosuria of six elderly diabetics.The reduction was, however, less than that achieved with aspirin, and would have no practical value in treatment.This difference between D.N.P. and salicylate in dia- betes makes it difficult to account for the action of both substances on the basis of inhibition of oxidative phos- phorylation, at least, without further specifications.My thanks are due to Miss M. McCombie, of the dietetic de- partment of the Western Infirmary, for supervision of the diets
Secondary Acute Myeloid Leukemia: Demographic, Physiopathogenic, Clinical and Therapeutic Comparative Study
Authors: Roberto Ovilla, Renee Leonor Crisp, Pamela E Baez-Islas, Jorge A Arbelbide, Sofia Grille, Lilián Díaz, Henry Idrobo, Alicia Enrico, Maria J Mela Osorio, Isolda I. Fernandez, Luciana C Ferrari, Nidia Zapata, Adrian A Ceballos-Lopez, Veronica Mena, Ana L Romero, Juan Carlos Serrano, Gabriela Vidal-Senmache, Fernando Barroso Duarte, Edit N Pintos, Mariana Rosenhain, Laura Kornblihtt, Natalia Tejeira, Breno Gusmao, Maria Elena Del Rocio Buenaño, Marcos Di Stefano, Matilde Boada, Alberto Gimenez Conca, Maria Perusini, Hernan Dick, Santiago Cranco, Maria Lucia Fuente, Alicia Beatriz Navickas, Maria M Moirano, Natalia Oliveira, Jacqueline Gonzalez, Mariana Bandín, Noelia Villaverde, Alejandro Suero, Juan Felipe Lasso, Nora Carrara, Xochitl Cota, Carolina Lazzarino, Maria Leticia Rapan, Marcelo Iastrebner, Latin-American MDS Group (GLAM), MDS and Acute Leukemia Sub-Commission Group Argentinian Society of Hematology
Journal: Blood (2019)
A Strong Correlation of the HIF1a mRNA Expression Level with the Total Expression of JAK2, As Well As a Decrease in Their Level Is Observed in Leukocytes of Patients with MPN and Lymphoproliferative Cancer
Authors: Igor A. Olkhovskiy, Aleksey S. Gorbenko, Marina A. Stolyar, Anna V. Komina, Evgeniy V. Vasiliev, Mikhail A. Mikhalev, Tatiana I. Olkhovik, Varvara I. Bakhtina
Journal: Blood (2019)