tbuckley/cabot-search huggingface dataset:
Effect of Once-Weekly Exenatide in Patients With Type 2 Diabetes Mellitus With and Without Heart Failure and Heart Failure–Related Outcomes
Authors: Marat Fudim, Jennifer White, Neha J. Pagidipati, Yuliya Lokhnygina, Julio Wainstein, Jan Murin, Nayyar Iqbal, Peter Öhman, Renato D. Lopes, Barry Reicher, Rury R. Holman, Adrian F. Hernandez, Robert J. Mentz
Journal: Circulation (2019)

Background: Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW’s effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points in patients with and without baseline HF and test the effects of EQW on recurrent HHF events. Methods: The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event component, first HHF, and repeat HHF, by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. Results: Of 14 752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio [HR], 0.86 [95% CI, 0.77–0.97]) and the composite outcome of all-cause death or HHF (HR, 0.89 [95% CI, 0.80–0.99]). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR, 1.05 [95% CI, 0.85–1.29]), while the risk of mortality was reduced with EQW in the no-HF group (HR, 0.79 [95% CI, 0.68–0.92]) with an interaction P value of 0.031. The reduction in all-cause death or HHF seen with EQW in patients without baseline HF (HR, 0.81 [95% CI, 0.71–0.93]) was not seen in patients with baseline HF (HR, 1.07 [95% CI, 0.89–1.29]; interaction P =0.015). First, plus recurrent, HHF was reduced in the exenatide group versus placebo (HR, 0.82 [95% CI, 0.68–0.99]; P =0.038). Conclusions: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. Clinical Trial Registration: https://www.clinicaltrials.gov . Unique identifier: NCT01144338.
Rapid Infusion with CT-P10 in Patients with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukaemia: Interim Six Month Follow-up from a European Non-Interventional Post-Authorisation Safety Study
Authors: Mark Bishton, Pier Luigi Zinzani, Scott Marshall, Veronica Conteh, Alicia Rodríguez Fernández, SooKyoung Kim, Young Nam Lee
Journal: Blood (2019)
Outcome of Patients with Hodgkin Lymphoma Treated with Brentuximab Vedotin for Relapse after Autologous Stem Cell Transplant: A Retrospective Analysis of the LWP-EBMT
Authors: Nikesh Dhiraj Chavda, Stephen Robinson, Ariane Boumendil, Irma Khvedelidze, Hervé Finel, Saad Akhtar, M S Rauf, Nadira Durakovic, Radovan Vrhovac, Maurizio Musso, Pauline Brice, Mutlu Arat, Didier Blaise, Matthew P. Collin, Joanna Romejko-Jarosinska, Aspasia Stamatoullas, Zubeyde Nur Ozkurt, Tadeusz Robak, Björn E Wahlin, Keith Wilson, Eleonora Alma, Rocco Pastano, Luca Castagna, Ali Bazarbachi, Hervé Ghesquieres, Andrei Colita, Silvia Montoto
Journal: Blood (2019)
The Lazy Eye
Authors: A. H. Briggs
Journal: BMJ (1947)

anxiety " received a bromide mixture, but the man with tonsillitis was more fortunate; he was given " appropriate treatment," apparently because he was accommodating enough to have "a normal ailment," whatever that means.So long as " adequately physical disorder " continues to be regarded as more " actual " and more in need of " appropriate treatment " than f sycho- neurotic illness, " the extent of neurosis " will remain considerably greater than it need be.-I am, etc., Glasgow.
Hydroxyurea Therapy to Prevent Incident Stroke Among Children with Sickle Cell Anaemia in Jamaica: The Extend Trial
Authors: Angela Rankine-Mullings, Marvin Ellsworth Reid, Deanne Soares, Carolyn Taylor-Bryan, Margaret Wisdom-Phipps, Karen Aldred, Teresa Latham, Jennifer Knight-Madden, Lesley King, Asha Badaloo, Adam Lane, Robert J. Adams, Russell E. Ware
Journal: Blood (2019)
Routine use of progesterone does not prevent miscarriage
Authors: Rob Cook, Vaughan Thomas, Rachel Taft
Journal: BMJ (2019)

The study Coomarasamy A, Devall AJ, Cheed V, et al. A randomised trial of progesterone in women with bleeding in early pregnancy N Engl J Med 2019;380:1815-24. This project was funded by the NIHR Health Technology Assessment Programme (project number 12/167/26). To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000792/miscarriage-not-prevented-by-routine-use-of-progesterone
Rituximab for Preventing Delayed Hemolytic Transfusion Reaction (DHTR) in Sickle CELL Adult Patients: Outcome of Transfusion and SIDE Effects in 58 CASES
Authors: Fabian Zanchetta-Balint, France Pirenne, Marc Michel, Armand Mekontso-Dessap, Matthieu Mahevas, Constance Guillaud, Keyvan Razazi, Elena Foïs, Frédéric Galactéros, Pablo Bartolucci, Anoosha Habibi
Journal: Blood (2019)
SURG-15. SURVIVAL OUTCOMES FOLLOWING RE-RESECTION FOR RECURRENT GLIOBLASTOMA MULTIFORME
Authors: Maeve Hennessy, Mohamed Dablouk, William Mullally, Philip O’Halloran, Stephen MacNally, Patrick Morris
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND While the treatment of primary Glioblastoma Multiforme (GBM) is well defined, the role of surgical resection in recurrent GBM is not firmly established.1 Treatment options for recurrent GBM include second-line chemotherapy, re-irradiation and surgical re-resection.2 This review examines current practice in a national neuro-oncology centre. AIMS: To investigate survival outcomes in patients undergoing surgical re-resection for recurrent GBM in our institution and to compare our findings to the relevant published literature. METHODS A retrospective review of our institution’s neuro-oncology database was performed. We evaluated all patients who underwent re-resection for recurrent GBM following standard adjuvant treatment between 2015–2018. Patients who did not have an initial diagnosis of Grade 4 GBM and patients who were re-operated on within one month were excluded. We analysed overall survival using Kaplan Meier curves. Patients not known to have died were censored to the last known alive date. We also examined factors which may affect patient outcome, including age, sex, extent of resection, tumour characteristics and tumour location. RESULTS 34 patients were eligible for inclusion into this study, of these 21 (61%) were male. Median age was 52. A radiologically confirmed initial resection of &gt; 80% was achieved in 52% of patients. Median time from initial surgery to re-resection was 13.5 months. Median survival from initial surgery was 28.6 months and median survival after re-resection was 9.5 months. CONCLUSION Re-operation appears to have a role in the management of recurrent GBM in carefully selected cases. Overall survival in this patient cohort remains poor and further studies into the benefit of re-resection in comparison to second-line chemotherapy and re-irradiation would be of value.
CBMT-45. SEX-SPECIFIC METABOLIC ADAPTIONS IN GLIOBLASTOMA
Authors: Jasmin Sponagel, Shanshan Zhang, Prakash Chinnaiyan, Joshua Rubin, Joseph Ippolito
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. GBM occurs more commonly in males, but female patients survive significantly longer. Understanding the molecular mechanisms that underlie those sex differences could support novel treatment strategies. In this regard, we found that male and female GBM patient samples differ in their metabolite abundance and that male patients exhibit a significantly higher abundance of TCA cycle metabolites. We confirmed those findings in a murine model of GBM, which has previously yielded important insights into sexual dimorphism in GBM. Strikingly, sex differences in TCA cycle flux were entirely driven by glutamine flux, not glucose flux, suggesting a sex-specific role for glutamine in GBM. Metabolic manipulation through glutamine deprivation resulted in a greater growth inhibition in male GBM cells. Glutamine itself can be utilized for anabolic reactions or it can be converted to glutamate by glutaminase. Only male GBM cells were sensitive to pharmacological glutaminase inhibition with BPTES or CB-839, suggesting that male GBM cells are glutamate dependent while female GBM cells are not. Concordantly, we found significantly higher glutaminase levels in male GBM cells. Furthermore, we found that numerous metabolites (including NADH, ATP, and glutathione) involved in cellular processes downstream of glutamate were more abundant in male GBM cells. In contrast, female GBM cells were resistant to low glutamine conditions and glutaminase inhibitors unless glutamine-synthase activity was disrupted, suggesting that glutamine synthesis might play a more prominent role in female GBM. Together, these data indicate that male and female GBM differ in their metabolic adaptions. Male GBM utilize glutamate to fuel the TCA cycle and mitochondrial activity while female GBM synthesize and utilize glutamine itself. This sexual dimorphism in metabolic reprogramming reveals novel sex specific metabolic targets for GBM and underlines the importance of considering sex in metabolic targeting approaches.
NCOG-01. NEUROCOGNITIVE FUNCTION (NCF) AND QUALITY OF LIFE (QOL) RESULTS FROM A PHASE II STUDY OF TEMOZOLOMIDE-BASED CHEMORADIOTHERAPY REGIMEN FOR HIGH RISK LOW-GRADE GLIOMAS
Authors: Jeffrey Wefel, Stephanie Pugh, Ali Choucair, Barbara Fisher, Sherry Fox, Christina Meyers, Lynn Ashby, Tom Mikkelsen, Jon Glass, Michael Yu, Steven Howard, Benjamin Movsas, Minesh Mehta
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND RTOG 0424 reported a 73.5% 3-year overall survival (OS) rate. This secondary analysis describes changes in NCF and QOL after therapy. METHODS Patients with HR-LGG were treated with radiation and concurrent and adjuvant temozolomide. Standardized NCF tests were performed at baseline, 6 and 12 months (mos). Rates of NCF decline were examined using the reliable change index on Hopkins Verbal Learning Test (HVLT), Trail Making Test (TMT), and Controlled Oral Word Association. Relationships between NCF and subjective cognitive concerns (MOS-Cognitive Function [MOS-CF] scale) were evaluated with Wilcoxon Rank Sum Test. QOL was assessed using FACT-Brain. Longitudinal modeling using maximum likelihood estimation evaluated predictors of change in QOL. Cox models assessed the association of baseline NCF with OS after adjusting for age, anticonvulsants, number of high risk factors, EORTC OS risk group, and tumor crossing the midline. RESULTS From 1/2005 to 8/2009, 129 evaluable patients were accrued, and 93 (72%) completed at least one NCF/QOL measurement with completers having better neurologic function than noncompleters (p=0.04). Compliance across measures was 55–59% and 54–57% at 6 and 12mos. Deterioration occurred in 50%/40% at 6mos/12mos, respectively, and was most frequent on HVLT (21%/20%), TMTA (29%/20%), and TMTB (22%/14%). Patients with HVLT deterioration at 12mos, compared to patients without deterioration, had significantly greater decrease in MOS-CF (p=0.01). No NCF test at baseline was independently associated with OS. FACT Emotional (p=0.02) and Functional Well-Being (p=0.004) subscales improved over time. EORTC OS high-risk group was associated with worse QOL on all subscales (p&lt; 0.05 to 0.001) except Emotional Well-Being, tumor crossing the midline was associated with worse Emotional Well-Being (p=0.04), and unmethylated MGMT status was associated with better Physical Well-Being (p=0.05). CONCLUSIONS Approximately half of patients with HR-LGG experience NCF decline in the first year after treatment with temozolomide-based concurrent chemoradiation. QOL remained stable or improved.
Serrated polyp detection rate and advanced adenoma detection rate from a US multicenter cohort
Authors: Jagpal S. Klair, Munish Ashat, Dane Johnson, Sumant Arora, Nirmal Onteddu, Jose G. Machain Palacio, Ronald Samuel, Mohammad Bilal, Avanija Buddam, Ashutosh Gupta, Alan Gunderson, Praveen Guturu, Kaartik Soota, Subhash Chandra, Arvind R. Murali
Journal: Endoscopy (2019)

Abstract Background Interval colorectal cancers may be associated with a low serrated polyp detection rate (SDR) and advanced adenoma detection rate (AADR). We aimed to determine the SDR and AADR for endoscopists in a United States multicenter cohort. Methods We included average-risk screening colonoscopies from five medical centers in the United States. Endoscopists with data on at least 100 average-risk screening colonoscopies were included. We calculated median SDR and AADR for endoscopists with adequate adenoma detection rates (ADRs) &gt; 25 %. We analyzed the relationship between ADR and SDR, and between ADR and AADR using nonparametric Spearman correlation coefficients, scatter plots, and linear regression. Results We included 3513 screening colonoscopies performed by 26 gastroenterologists. The mean age of patients was 56.8 years (SD 7.4) and 1585 (45 %) were male. All but one endoscopist had an ADR above 25 %. There was a significant positive but modest correlation between ADR and SDR (rho = 0.67, P &lt; 0.01), and between ADR and AADR (rho = 0.56, P &lt; 0.01). For endoscopists with an adequate ADR, median (interquartile range) ADR was 43 % (32.0 % – 48.6 %), median SDR was 8.4 % (7.3 % – 11.4 %), and median AADR was 9.3 % (6.4 % – 12.6 %). Conclusion A significant percentage of endoscopists have either a low SDR or low AADR despite an adequate ADR, justifying the need for separate SDR and AADR benchmarks. Based on our multicenter cohort, endoscopists with adequate ADRs had a median SDR and median AADR of about 8 % and 9 %, respectively.
Vertebro-basilar Ischaemia
Authors: T. Lehoczky
Journal: BMJ (1964)

abnormality noted on examination.The haemo- globin value was 12.6 g./ 100 ml., with marked anisocytosis and many nucleated erythrocytes, spherocytes, and aberrant forms in a smear of peripheral blood.Of the erythrocytes approximately 40% were reticulocytes, and approxi- mately 80% contained Heinz bodies.The total serum bilirubin content was 5.3 mg./ 100 ml. and the conjugated serum bilirubin content 0.4 mg./100 ml.The mother's blood group was 0, Rh negative and the infant's blood group 0, Rh positive.The direct Coombs test was negative.The glucose-6-phosphate dehydrogen- ase (G6PD) activity by the method of Zinkham' was 260 units 100 ml. of erythrocytes.After transfusion of 100 ml. of blood the in- fant's condition improved rapidly.On 23 December the child was free of jaundice and purpura, the haemoglobin level was 23 g./100 ml., the erythrocytes were of normal appearance, and thrombocytes were present in normal numbers.The child has progressed well until the present time, with haemoglobin levels and thrombocyte counts within the normal range.Both parents are of Anglo-Saxon racial ex- traction.Over the last three weeks of pregnancy the mother had suffered from urinary symptoms and some oedema.For 15 days before delivery she had received sulphamethizole, 0.5 g. every four hours, and chlorothiazide, 0.5 g. daily.Case 2.-This female infant was first seen on 29 July 1963 at the age of 4 days, with a history of slowly increasing jaundice from the age of 24 hours.The infant was believed to be three weeks premature, but the birth weight was 3.6 kg.Gross jaundice was the only abnormality on physical examination.The total serum bilirubin content was 16.5 mg./100 ml., and the conju- gated serum bilirubin content less than 0.5 mg./ 100 ml.The haemoglobin level was 19.0 g./100 ml., reticulocytes comprised about 3 % of the erythrocytes, and Heinz bodies were present in approximately 20% of the erythrocytes.No
Incidence of High-Grade Hematologic Toxicities and Hypertension in Patients with Hematological Malignancies Treated with Ibrutinib
Authors: Chandler Graf, Anita Sultan, Donald P. Quick, Bradley J. Grant, Sriman Swarup, Thura Win Htut, Pwint Phyu Hlaing, Myat Min Han, Yin Mon Myat, Fred Hardwicke, Sanjay Awasthi, Nicholas D'Cunha, Lukman Tijani, Kyaw Zin Thein
Journal: Blood (2019)
Comprehensive Geriatric Assessment in Consecutive Newly-Diagnosed Elderly Multiple Myeloma Patients in China: A Multicentered, Prospective, Non-Interventional Study
Authors: Yuan Yao, Dehui Zou, Aijun Liao, Xiaoxia Chu, Wei Wang, Xinan Cen, Lijuan Chen, Li Bao, Rong Fu, Hui Liu, Chunyan Sun, Luqun Wang, Fengyan Jin, Hua Yan, Chenglu Yuan, Liangming Ma, Guangxun Gao, Jinqiao Zhang, Da Gao, Jianda Hu, Jianxia He, Ai-lin Zhao, Lu Zhang, Dao-Bin Zhou, Jian Li
Journal: Blood (2019)
Somatic Mutations and Loss of Heterozygosity of HLA Genes Are Frequently Occurred and Tightly Associated with Poor Prognosis in Adult T Cell Leukemia-Lymphoma
Authors: Keita Tamaki, Satoko Morishima, Shingo Suzuki, Atsuko Shigenari, Ikumi Nomura, Yutaro Yokota, Kazuho Morichika, Yukiko Nishi, Sawako Nakachi, Shiki Okamoto, Kennosuke Karube, Takuya Fukushima, Takashi Shiina, Hiroaki Masuzaki
Journal: Blood (2019)
RDNA-12. THE FANCONI ANAEMIA (FA) PATHWAY AND GLIOBLASTOMA: A NEW FOUNDATION FOR DNA DAMAGE RESPONSE TARGETED COMBINATIONS
Authors: Ola Rominiyi, Katie Myers, Natividad Gomez-Roman, Nikita Lad, Dawoud Dar, David Jellinek, Anthony Chalmers, Thomas Carroll, Beining Chen, Yahia Al-Tamimi, Spencer Collis
Journal: Neuro-Oncology (2019)

Abstract Treatment resistance in glioblastoma is underpinned by highly interconnected DNA damage response (DDR) processes. The FA-pathway is a fundamental DDR process required for the resolution of replication fork impeding lesions, and we have previously shown that it is inactive in normal brain, but is re-activated in glioblastoma, providing a cancer-specific target for combination DDR therapies. Here, we find that elevated FA-pathway gene expression in gliomas is associated with poor survival (-17.1% 5-year OS, p&lt; 0.0001, n=329–REMBRANT). Furthermore, patient-derived glioblastoma stem cell (GSC) populations, which drive therapeutic resistance, display high FA-pathway expression relative to paired bulk tumour cell populations (mean 2.3-fold higher across genes, p=0.0073). We further show that inhibition of a single DDR process (FA-pathway, PARP, ATR or ATM) increases the susceptibility of glioblastoma cell lines and patient-derived GSCs to current adjuvant therapy. Importantly, clinically approved PARP inhibitor (PARPi) monotherapy stimulates robust FANCD2 mono-ubiquitination, supporting a role of FA-pathway activation in response to current DDR-targeted therapy. In clinically-relevant 3D GSC models, simultaneous inhibition of the FA-pathway (FAPi) and PARP or ATR enhanced temozolomide sensitisation compared to a single DDR inhibitor (DDRi). Furthermore, combined FAPi+PARPi consistently conferred radiosensitisation whilst combined FAPi+ATRi led to a profoundly radiosensitising effect; e.g. sensitizer enhancement ratio (SER0.37) of 3.23 (3.03–3.49, 95% CI). Furthermore, comparison of α/β ratio enhancement suggests dual-DDRi strategies fundamentally alter the response of GSCs, whilst single cell gel electrophoresis &amp; immunofluorescence studies suggest FA-pathway based DDRi combinations profoundly delay the resolution of IR-induced DNA strand breaks at 6 hours post-treatment, with increased persistent DNA double strand breaks at 24 hours. In conclusion, simultaneously targeting the FA-pathway and interconnected DDR processes represents an appealing therapeutic strategy. Additionally, constitutive lack of FA pathway function in some tumours, could serve as a novel predictive biomarker for patient response to PARPi and ATRi currently in clinical trials.
Genomic Analysis of R2CHOP-Treated DLBCL Reveals a High-Risk Population Driven By Inflammatory Pathways
Authors: Keenan T. Hartert, Kerstin Wenzl, Jordan Krull, Michelle Manske, Vivekananda Sarangi, Yan Asmann, Melissa C Larson, Matthew J Maurer, Susan L. Slager, William R. Macon, Rebecca L. King, Andrew L. Feldman, Anita K Gandhi, Brian K. Link, Thomas M. Habermann, Zhi-Zhang Yang, Stephen M Ansell, James R. Cerhan, Thomas E. Witzig, Grzegorz Nowakowski, Anne J Novak
Journal: Blood (2019)
Allogeneic CD34-Selected HSCT Following CAR T-Cells Is Associated with Low TRM and Favorable OS in Pediatric/Young Adult Patients with Relapsed/Refractory B-ALL
Authors: Vanessa Fabrizio, Farid Boulad, Maria I. Cancio, Meghan A. Higman, Steven P. Margossian, Audrey Mauguen, Susan Prockop, Andromachi Scaradavou, Niketa C. Shah, Barbara Spitzer, Nick Yeager, Nancy A. Kernan, Richard O'Reilly, Jaap Jan Boelens, Kevin J. Curran
Journal: Blood (2019)
Liquid Biopsy Is Useful to Identify the Genetic Profile of NHL-B at Diagnosis in Different Histological Subtypes
Authors: Mariana Bastos-Oreiro, Julia Suárez González, Natalia Carolina Carrión, Cristina Andres, Solsireey Moreno, Diego Carbonell, María Chicano Lavilla, Gillen Oarbeascoa, Francisco Diaz Crespo, Javier Menarguez, José Luis Díez-Martín, Ismael Buño, Carolina Martínez-Laperche
Journal: Blood (2019)
Prevalence of Inherited Cancer Predisposition Mutations in a Cohort of Older AML Patients Enrolled on the Beat AML Master Trial
Authors: Uma Borate, Fei Yang, Richard D. Press, Dean Pavlick, Luke Juckett, Anupriya Agarwal, Amy Burd, Alice S. Mims, Eytan M. Stein, Prapti A. Patel, Maria R. Baer, Wendy Stock, Gary J. Schiller, William Blum, Paul J Shami, Mark Litzow, James M. Foran, Nyla A. Heerema, Leonard Rosenberg, Sonja Marcus, Ashley Owen Yocum, Mona Stefanos, John C. Byrd, Brian J. Druker, Jo-Anne Vergilio, Ross L. Levine
Journal: Blood (2019)
The Clinical Significance of a Novel microRNA Signature in Multiple Myeloma
Authors: Pinelopi I Artemaki, Aristea-Maria Papanota, Paraskevi Karousi, Christine Liacos, Christos K. Kontos, Dimitris Patseas, Maria-Alexandra Papadimitriou, Evangelos Eleutherakis-Papaiakovou, Margaritis Avgeris, Nikolaos Kanellias, Tina Bagratuni, Maria Roussou, Ioanna Dialoupi, Eftathios Kastritis, Maria Gavriatopoulou, Meletios A. Dimopoulos, Andreas Scorilas, Evangelos Terpos
Journal: Blood (2019)