tbuckley/cabot-search huggingface dataset:
CBMT-44. COMPREHENSIVE CHARACTERIZATION OF THE INTRINSIC APOPTOTIC MACHINERY REVEALS THE MOLECULAR BLOCKS RESPONSIBLE FOR RESISTANCE TO CELL DEATH IN GLIOBLASTOMA
Authors: Elizabeth Fernandez, Wilson Mai, Nicholas Bayley, Linda Liau, Timothy Cloughesy, Anthony Letai, David Nathanson
Journal: Neuro-Oncology (2019)

Abstract Conventional therapies (e.g., temozolomide (TMZ), Irradiation (IR)) transiently halt tumor growth of glioblastoma (GBM) but fail to induce cell death through apoptosis. Consequently, the inability to kill GBM tumor cells ultimately leads to disease progression and a poor patient survival. The precise molecular mechanisms by which GBM are refractory to apoptosis remain enigmatic. We preformed BH3 profiling to functionally characterize the intrinsic apoptotic machinery and define the molecular ‘blocks’ that obstruct GBM apoptosis under both basal and treatment states. Using a molecularly diverse panel of freshly purified patient tumors, patient-derived neurospheres and patient-derived orthotopic xenografts, we identified that nearly all GBMs have two anti-apoptotic blocks, BCL-xL and MCL-1, which are essential for GBM survival in an untreated state. TMZ or IR (TMZ/IR) disabled the MCL-1 block in a subset of GBMs, leaving tumors exclusively dependent on BCL-xL for survival. Mechanistic studies revealed that TMZ/IR treatment induced p53-dependent expression of the pro-apoptotic protein, PUMA, which subsequently bound to and neutralized MCL-1. Consequently, pharmacological inhibition of BCL-xL in combination with TMZ/IR initiated intrinsic apoptosis and was synergistically lethal in p53 wild-type GBM. These studies identify the existence of two anti-apoptotic proteins that are critical for GBM survival, which can be therapeutically exploited in a molecularly defined subset of GBMs for tumor eradication.
Identification of Gene Expression Signatures in Leukemia Stem Cells and Minimal Residual Disease Following Treatment of Adverse Risk Acute Myeloid Leukemia
Authors: Ghayas C. Issa, Christopher B. Benton, Vakul Mohanty, Yifei Shen, Zoe Alaniz, Feng Wang, P. Andrew Futreal, Wei Wang, Jeffrey L. Jorgensen, Nicholas Navin, Marina Y Konopleva, Ken Chen, Michael Andreeff
Journal: Blood (2019)
Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry
Authors: Hans C. Lee, Sikander Ailawadhi, Cristina Gasparetto, Sundar Jagannath, Robert M. Rifkin, Brian G.M. Durie, Mohit Narang, Howard R. Terebelo, Kathleen Toomey, James W. Hardin, Lynne I. Wagner, James L. Omel, Shankar Srinivasan, Liang Liu, Mazaher Dhalla, Amit Agarwal, Rafat Abonour
Journal: Blood (2019)
Incidence of Bloodstream Infections, Length of Hospital Stay, and Survival in Patients With Recurrent<i>Clostridioides difficile</i>Infection Treated With Fecal Microbiota Transplantation or Antibiotics
Authors: Gianluca Ianiro, Rita Murri, Giusi Desirè Sciumè, Michele Impagnatiello, Luca Masucci, Alexander C. Ford, Graham R. Law, Herbert Tilg, Maurizio Sanguinetti, Roberto Cauda, Antonio Gasbarrini, Massimo Fantoni, Giovanni Cammarota
Journal: Annals of Internal Medicine (2019)

Clostridioides difficile infection (CDI) is a risk factor for bloodstream infection (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain.To assess incidence of primary BSI in patients with recurrent CDI treated with FMT versus antibiotics.Prospective cohort study. Patients treated with FMT and those treated with antibiotics were matched on propensity score.Single academic medical center.290 inpatients with recurrent CDI (57 patients per treatment in matched cohort).FMT or antibiotics.The primary outcome was primary BSI within 90 days. Secondary outcomes were length of hospitalization and overall survival (OS) at 90 days.Of the 290 patients, 109 were treated with FMT and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Because of differences in the patients treated with FMT versus antibiotics in many baseline characteristics, including number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Risk for BSI was 23 percentage points (95% CI, 10 to 35 percentage points) lower in the FMT group; the FMT group also had 14 fewer days of hospitalization (CI, 9 to 20 fewer days) and a 32-percentage point increase in OS (CI, 16 to 47 percentage points) compared with the antibiotic group.Nonrandomized study with potential for unmeasured or residual confounding; limited generalizability of the propensity score-matched cohort.In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.None.
Iron Chelation and Ferritin below 500 Mcg/L in Transfusion Dependent Thalassemia: Beyond the Limits of Clinical Trials
Authors: Natalia Scaramellini, Carola Arighi, Alessia Marcon, Dario Consonni, Elena Cassinerio, Giovanna Graziadei, Maria Domenica Cappellini, Irene Motta
Journal: Blood (2019)
De Morgan's Spots
Authors: L. Wertheim
Journal: BMJ (1947)

BIUTISH I ~~~~~~~~~~~~~~~~~~~~~~~~~~~~ME JOURNALof his blood count elsewhere had given no signs of hyper- eosinophiUa, I had it re-exatnined in October, when a "hyper- coslnophil phase" of 11% was found.t. R. Rugeley publihsed a paper on allergic causes of prutitus ani recently (Annals df Allergy, 1946, 4, 374 and 396) and reported about 14 cases of pruritus ani in which a connexion with allergic causes was revealed and rapid imtprovement achieved by' treatment on these lines, whereas the conven- tional treatment, tried befote, had proved to be unsuccessful.He holds the opinion that excoriationis, oedema of the skin, thickening, or exudation vary in intensity, and that papillitis, fissures, and other changes thought to be causative factors are often secondary and not pritnary changes.He recotnends strongly that allergic causes of prutitus ani should be investi- gated before radical procedures are suggested, such as surgical interference, x-ray treatment, local injections, diisions of nerves, or tattooing of the anal margins with anaesthetics.-I am, etc., London, W.1.E. M. FRAENktL.Congenital Hepatic-duct Malformation Sitt,-Length of survival nmay warrant recording the follow- ing case.A female child 10 months old had been jaundiced since her normial birth.Weight records were: 7 lb.(3.1 kg.) at birth, 9 lb.(4 kg.) at 6 nionths, 12 lb. (5.4 kg.) at 10 months.Absence of breast milk had resulted in cows' milk feedings.Three older children were healthy.The child was lively and profoundly jaundiced.Her spleen
HOUT-07. ASSOCIATION BETWEEN BASELINE BODY MASS INDEX (BMI) AND OUTCOMES FOR PATIENTS WITH GLIOBLASTOMA
Authors: Jessica Chew, Olivier Morin, Steve Braunstein
Journal: Neuro-Oncology (2019)

Abstract OBJECTIVES This single institution retrospective study aims to evaluate the association between body mass index (BMI) and survival in glioblastoma (GBM). METHODS Patients were identified using a single institution cancer registry. Baseline height and weight were obtained at first clinical visit after diagnosis. Inclusion criteria were GBM diagnosis after 1999 with available height and weight data. Follow up was through July 2018. RESULTS 779 patients were included who had available BMI data. Median age was 58 (IQR 48–66). 38% of patients were female and 62% were male. Median overall survival (OS) was 1.34 years (IQR 0.78–2.12) and median BMI was 26.01 (IQR 23.3–29.1). There was no strong linear correlation between OS and BMI using Pearson correlation (r=0.045). Patients with higher BMI had significantly improved OS when comparing the top 50% to bottom 50% (2.20 vs 1.89 years, p=0.03) and top 25% to bottom 25% (2.25 vs 1.84 years, p=0.03). When comparing patients classified as overweight or obese (BMI &gt;/= 25) to those within normal range or below (BMI &lt; 25), there was a trend towards increased OS (2.14 vs 1.90 years, p=0.075). There was no significant trend for BMI when comparing patients with higher OS with lower OS. There was also no significance for BMI on Cox proportional hazard multivariate analysis. CONCLUSIONS There was no significant linear correlation between BMI and survival for GBM patients, although there appears to be statistically significant improved survival benefit for patients with higher BMI compared to patients with lower BMI. Further investigation is warranted to explore this finding and if BMI could be used as a potential prognostic marker for GBM.
Obinutuzumab Alone or Combined with Chemotherapy in Previously Untreated (Fit or Unfit) or Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) Patients: Final Results from the Phase IIIb GREEN Safety Study with a Focus on Efficacy
Authors: Stephan Stilgenbauer, Francesc Bosch, Véronique Leblond, Osman Ilhan, Jens Kisro, Béatrice Mahé, Eva Mikuskova, Dzhelil Osmanov, Gianluigi Reda, Eugen Tausch, Marcin Wójtowicz, Thomas Perretti, Marlies EHM Van Hoef, Robin Foà
Journal: Blood (2019)
Immune Landscapes Predict Chemotherapy Resistance and Anti-Leukemic Activity of Flotetuzumab, an Investigational CD123×CD3 Bispecific Dart® Molecule, in Patients with Relapsed/Refractory Acute Myeloid Leukemia
Authors: Jayakumar Vadakekolathu, Mark D. Minden, Tressa Hood, Sarah E. Church, Stephen Reeder, Heidi Altmann, Amy H Sullivan, Elena J Viboch, Tasleema Patel, Narmin Ibrahimova, Sarah E. Warren, Andrea Arruda, Marc Schmitz, Yan Liang, Alessandra Cesano, A. Graham Pockley, Peter Valk, Bob Löwenberg, Martin Bornhäuser, Sarah K. Tasian, Michael P. Rettig, Jan K Davidson-Moncada, John F. DiPersio, Sergio Rutella
Journal: Blood (2019)
Oral Mucositis Is Associated with Distinctive Patterns of Oral Microbiota Injury in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Roni Shouval, Adi Eshel, Ivetta Danylesko, Bar Dubovski, Joshua A Fein, Shalev Fried, Mika Geva, Elizaveta Kouniavsky, Amir A Kuperman, Yoram Louzoun, Omry Koren, Arnon Nagler
Journal: Blood (2019)
EPID-08. TYPES OF BRAIN CANCER IN THE CENTRAL TEXAS MILITARY POPULATION
Authors: Jennifer Murillo, Ankita Brahmaroutu, Wencong Chen, Jared Benge, Ekokobe Fonkem
Journal: Neuro-Oncology (2019)

Abstract Multiple studies have demonstrated a correlation with military service and brain tumors, both for primary tumors and meningiomas. However, there is little comprehensive research on tumor types in the US military population. We evaluated our local brain tumor bank to identify types and correlates of brain tumors in a military vs. civilian population in central Texas. PURPOSE The purpose of our research was to describe brain cancers in the military population when compared to nonmilitary population in our local database. METHODS Retrospective data was derived from our brain tumor bank at the Baylor Scott &amp; White in central Texas. Tumors were classified based on final histologically confirmed diagnosis when possible. Demographics and correlates. We obtained military background by chart review of notes, occupation, insurance provider and relationship to insured in the electronic medical record. RESULTS Data from 53 veterans and 170 non-veterans were analyzed. The most common tumor type in Veterans was glioblastoma multiforme (20.75%) followed by metastatic lesions (18.87%), meningiomas (16.98%) and adenomas (13.21%). There was no statistically significant difference in distribution of tumor types between civilians and controls. Demographic analysis revealed an older age of diagnosis in Veterans than civilians for the top three most common tumor types with glioblastoma multiforme (67.64 vs 61.65) with a difference of 5.99 years; metastatic lesions (69.4 vs 61.22) with a difference of 8.18 years and meningiomas (63.88 vs 57.57) with a difference of 6.31 years. (military versus civilians average age, respectively). CONCLUSION The age of onset for the three most common types of tumors were older in the Veteran population than civilians by an average of 6.82 years. More research into the older age of diagnosis for the Veterans should be further explored. Our research did not find any correlation between military service and tumor types as previous studies have shown.
Efficacy of Elotuzumab Based Combinations in Patients with Multiple Myeloma - a Systematic Review
Authors: Arafat Ali Farooqui, Ahmad Anjum, Muhammad Saad Farooqi, Talha Bin Farooq, Tanveer Shaukat, Aqsa Ashraf, Humaira Sarfraz, Zunairah Shah, Muhammad Junaid Tariq, Faiz Anwer
Journal: Blood (2019)
A Phase 2 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody (Ab), in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL)
Authors: Max S. Topp, Johannes Duell, Jingjin Li, Vladimir Jankovic, Israel Lowy, David Sternberg, Lieve Adriaens, Mary Peterman, Srikanth R. Ambati, Rajat Bannerji
Journal: Blood (2019)
RARE-12. EARLY FOCAL RADIOTHERAPY AND TEMOZOLOMIDE FOLLOWING COMPLETE RESECTION APPEAR SUPERIOR TO INTENSIVE CHEMOTHERAPY IN CHILDREN WITH EMBRYONAL TUMORS WITH MULTILAYERED ROSETTES (ETMR)
Authors: Irene Slavc, Lisa Mayr, Johannes Gojo, Andreas Peyrl, Amedeo Azizi, Karin Dieckmann, Christine Haberler, Thomas Czech
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Embryonal tumor with multilayered rosettes (ETMR) is an extremely rare entity characterized by LIN28A expression and alterations in the C19MC locus. ETMRs predominantly occur in young children and have a dismal prognosis. We report on our single institution experience in seven consecutive patients. METHODS Between 2006 and 2016, seven patients were diagnosed with ETMR. Diagnosis was established prospectively by characteristic histopathologic features, LIN28A immunostaining and amplification of the C19MC region in five patients and retrospectively confirmed in two additional patients originally diagnosed as central nervous system primitive neuroectodermal tumor. Tumor location was supratentorial in all patients. Median age at diagnosis was 25 months (range 5–38). Male to female ratio was 1:6. RESULTS All patients received gross total tumor resection and four patients were treated with intensive chemotherapy regimens including high-dose chemotherapy in three patients. Four patients recurred after a median of 6 months (range 2–11 months) and all except one patient who died after high-dose chemotherapy, succumbed to their disease after a median of 13 months (range 7–28 months). Consequently, the two most recent patients were treated with gross total tumor resection, primary focal radiotherapy and concomitant temozolomide followed by temozolomide for one year. Due to the high risk of leptomeningeal dissemination intraventricular chemotherapy was administered to all except one patient. Both patients who were treated with primary focal radiotherapy are in continuous complete remission 41 and 36 months after diagnosis. CONCLUSION Gross total resection followed by early focal radiotherapy, temozolomide, and intrathecal chemotherapy seem to be superior to intensive chemotherapy including high-dose chemotherapy.
Stitch-assisted Zenker’s diverticulotomy technique using a flexible diverticuloscope
Authors: Guilherme Francisco Gomes, Rafael William Noda, Andre Marussi Morsoletto, Leandro Kashiwagui, Raul Anselmi Junior, Christiano Claus
Journal: Endoscopy (2019)

A 55-year-old man presented with a 10-year history of progressive dysphagia, mainly for solids. He had previously undergone two unsuccessful attempts at an endoscopic diverticulotomy at another institution. Because of his persistent dysphagia, contrast radiography of the esophagus and upper gastrointestinal endoscopy were performed, and a 5-cm Zenker’s diverticulum was identified. A new flexible endoscopic procedure was proposed for the patient, which consisted of transoral stapling of the diverticular septum using an Echelon Flex stapler (Ethicon, Cincinnati, Ohio, USA) ([Fig. 1 a]) while traction on the septum was maintained with two stitches.
Carbapenemase-Producing Enterobacteriaceae (CPE) Bloodstream Infections (BSI) in Neutropenic Patients (pts) with Acute Leukemia (AL). Comparison of 2 Strategies
Authors: Marcos Lemos, Rebeca Brito, Margarida Fevereiro, Mariana L. Fernandes, Filipa Saraiva, Susana G Pereira, Leonor Sarmento, Alexandra Monteiro, Aida B Sousa
Journal: Blood (2019)
Treatment of Ulcerative Colitis
Authors: F. C. Walker
Journal: BMJ (1965)

no immigrant leaves the port health area un- checked.May I suggest that in addition to the members already recruited for the B.M.A. working party the services of an experienced mass radiography unit director are secured.The planning and organization of a large number of people through a chest x-ray apparatus is a part of the normal work of a mass radiography unit medical director.
TMIC-47. INHIBITION OF GLIOBLASTOMA GROWTH THROUGH TUMOR-MICROENVIRONMENT CROSSTALK USING CLINICALLY SUITABLE NANOBIOCONJUGATE
Authors: Anna Galstyan, Dmytro Klymyshyn, Rameshwar Patil, Hui Ding, Ekaterina Shatalova, Eggehard Holler, Alexander Ljubimov, Keith Black, Tao Sun, Julia Ljubimova
Journal: Neuro-Oncology (2019)

Abstract Tumor environment in glioblastoma (GBM) is a dynamic interactive complex between tumor, immune and stem cells and extracellular matrix (ECM). In 226 patient glioma samples, we found a clinical correlation between expression of tumor vascular laminin-411 (α4β1γ1) and cancer stem cell (CSC) markers: Notch pathway members, CD133, Nestin, and c-Myc, with faster tumor recurrence and shorter survival of patients (Tao S, et al, Cancer Res., 2019). Novel nanotechnology approach to block trimeric ECM laminin-411 was developed for GBM treatment in experimental and preclinical models on human U87MG and LN229, and patient-derived TS543 and TS576 GBM cell lines. Nanobioconjugates (NBC) based on natural polymer, poly(β-L-malic acid), with antisense against laminin-411 α4 and β-chains, endosome escape unit (Ding H, et al, PNAS, USA, 2010), antibodies for blood-brain barrier (BBB) crossing and tumor targeting was characterized for toxicity and biodistribution according to FDA guidelines. Ex vivo depletion of laminin-411 α4 and β1 chains with CRISPR/Cas9 in human GBM cells led to reduced growth of intracranial tumors in mice, and significantly increased survival in hosts compared to mice with untreated cells. A nanobioconjugate potentially suitable for clinical use and capable of crossing BBB was designed to block laminin-411 expression. In biodistribution studies the NBC labeled with 125I on tyrosines of attached antibodies was accumulated in GBM but not in healthy brain tissue. Nanobioconjugate treatment of mice carrying intracranial GBM significantly increased animal survival and inhibited multiple CSC markers, Notch signaling system through the b1 integrin-Dll4 (Notch ligand) pathway. No toxicity revealed in 4 naïve Cynomolgus macaques after administration of three therapeutic 1X and acute 10X dosages of NBC. Conclusion: An efficient strategy of GBM treatment was developed via targeting a critical component of the tumor microenvironment, laminin-411, which is independent of heterogeneous genetic mutations in glioblastomas. Support: NIH grants U01CA151815, R01CA188743, R01CA206220, R01CA209921.
Treatment of Newly Diagnosed Moderate or Severe Chronic Graft-Versus-Host Disease with Prednisone and Everolimus (PredEver first): A Prospective Multicenter Phase IIa Study
Authors: Francis Ayuketang Ayuk, Eva Maria Wagner, Daniel Wolff, Stephanie von Harsdorf, Christian Koenecke, Herbert G. Sayer, Nicolaus Kroeger
Journal: Blood (2019)
NIMG-58. SEX DIFFERENCES IN CONTRAST-ENHANCING GLIOMAS AT PRESENTATION
Authors: Sandra Johnston, Aditya Khurana, Paula Whitmire, Akanksha Sharma, Andrea Hawkins-Daarud, Sara Ranjbar, Leland Hu, Joshua Rubin, Kathleen Egan, Peter D Canoll, Alyx Porter, Maciej Mrugala, Priya Kumthekar, Kristin Swanson
Journal: Neuro-Oncology (2019)

Abstract Sex differences in brain tumor related epilepsy (BTE) as an initial symptom of glioma are rarely investigated. Sex differences are being explored with increased interest more recently. Epidemiological studies have generally indicated overall incidence of epilepsy to be slightly higher in males than females, but a higher incidence of idiopathic generalized epilepsy has been seen in females in some studies. Clinicians regularly face the challenge of anti-epileptic drug prescription determination in patients with newly identified brain mass and would greatly benefit from knowing clinical characteristics in BTE. We analyzed clinical characteristics in patients with pathologically-determined glioma with known seizure status at clinical presentation using non-parametric and Fisher’s Exact tests with the entire cohort and male and female separately. From our clinical data repository, we identified 223 patients (females, n=86 (39%); males, n=137 (61%)) divided by those that presented with seizure (SP, n=96, 43%; F, n= 28; M, n= 68) and those that presented without seizure (nSP, n=127, 57%, F n=58, M n=69). In sex-specific analysis males had a significantly (x2=6.28, p=0.01) higher proportion of SP (49.6%) than females (32.6%). There was a dependence between seizure presentation status and tumor grade in males (x2=5.94, p=0.015). Tumor kinetics in the female cohort showed significantly (p&lt; 0.0001) more diffuse tumors in SP compared to nSP. Right-sided tumors were predominantly nSP, while left-sided tumors were split more evenly between SP and nSP. The predominance of nSP among right-sided tumors seems to be driven by females (74%), male right-sided tumors were split more evenly between SP and nSP. Seizure status is dependent on tumor location for the combined cohort, however not for males (x2=5.23, p=0.16) or females (x2=4.34, p=0.23). Clearly there are sex differences and similarities in clinical characteristics at glioma presentation. Further characterization could lead to improved adherence of national standards for AED prescription.
AML: Negative Prognostic Impact of Early Blast Persistence Can be Overcome By Subsequent Remission Induction
Authors: Jana Ihlow, Sophia Gross, Leonie Busack, Alma Herneth, Igor-Wolfgang Blau, Ioannis Anagnostopoulos, Michaela Schwarz, Anne Floercken, Lars Bullinger, Jörg Westermann
Journal: Blood (2019)
Safety and Preliminary Clinical Activity of REGN5458, an Anti-Bcma x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Dennis Cooper, Deepu Madduri, Suzanne Lentzsch, Sundar Jagannath, Jingjin Li, Anita Boyapati, Lieve Adriaens, Dhruti Chokshi, Min Zhu, Israel Lowy, David M. Weinreich, George D. Yancopoulos, Manish Sharma, Maria Karasarides, David Sternberg
Journal: Blood (2019)
Tyrosine Kinase Inhibitors (TKIs) Targeting Syk and BTK Signaling Differentially Affect PI3K Signalosome Organization and Platelet Function
Authors: Tony Zheng, Elizabeth R Lofurno, Sarah Elgamal, Alexander R Melrose, Jiaqing Pang, Joseph J Shatzel, Owen J T McCarty, Joseph Aslan
Journal: Blood (2019)