tbuckley/cabot-search huggingface dataset:
The impact of randomized trial results and altered regulatory policies on ESA use, transfusions, and thrombosis: A longitudinal analysis over a 3-year period of resource utilization data from a large comprehensive oncology program
Authors: I. Shapira, H. Raftopoulos, R. J. Gralla, K. Pelc, K. Gleason
Journal: Journal of Clinical Oncology (2009)

6611 Background: Recent randomized trials and meta-analyses demonstrated unexpected findings with ESA use with chemotherapy. Results revealed an overall increase in thrombosis rates with the use of ESAs as well as decrements in survival in some malignancies, particularly with breast and head and neck cancers (Bohlius, JNCI, 2006; Raftopoulos, Proc ASCO, 2008; Bennett, JAMA 2008). Benefits with ESA use have resulted in an average 1–1.5g/dl rise in hemoglobin. The impact on quality of life and fatigue remains controversial. Toxicity issues have led to restricted labeling by the FDA and reimbursement decisions by the Centers for Medicare and Medicaid Services (CMS). Despite these risks associated with the use of ESAs, concerns regarding increased use of transfusions remain prominent. A longitudinal study to assess the impact of these ESA policies was conducted to assess the demand on transfusion services and ESA use over time. Methods: Our center comprises a large comprehensive combined hematology and oncology program and has a non- restrictive transfusion policy, allowing physician discretion and the capacity to accommodate all out-patient transfusions. We analyzed ESA use over the 3 year period, 2006–2008. 2006 functioned as our baseline; 2007 was the year of initial FDA and CMS changes; 2008 allowed us to see if practice changes would persist. Results: We present in the table below, our data on ESA use and transfusion resource utilization. Conclusions: With over 60,000 patient visits during 3 years, longitudinal assessment reveals a continued, marked decrease in ESA use. Despite liberal transfusion policies, there has been little effect on transfusion rates. Increases in transfusions are commensurate with a rise in patient visit volume. We are now evaluating whether this marked decrease in ESA use translates into decreased thrombosis rates over this 3-year period at our cancer center. [Table: see text] No significant financial relationships to disclose.
Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study
Authors: Sandra Cohen, Jean Roy, Silvy Lachance, Jean-Sébastien Delisle, Anne Marinier, Lambert Busque, Denis-Claude Roy, Frédéric Barabé, Imran Ahmad, Nadia Bambace, Léa Bernard, Thomas Kiss, Philippe Bouchard, Pierre Caudrelier, Sévérine Landais, Fannie Larochelle, Jalila Chagraoui, Bernhard Lehnertz, Sophie Corneau, Elisa Tomellini, Jeroen J A van Kampen, Jan J Cornelissen, Maude Dumont-Lagacé, Mégane Tanguay, Qi Li, Sébastien Lemieux, Peter W Zandstra, Guy Sauvageau
Journal: The Lancet Haematology (2019)
VWF and FVIII Levels after Desmopressin Are Associated with the Bleeding Phenotype in Type 1 VWD
Authors: Ferdows Atiq, Lisette M. Schütte, Agnes E.M. Looijen, Johan Boender, Moniek P.M. de Maat, Marieke J.H.A. Kruip, Frank W.G. Leebeek
Journal: Blood (2019)
Cell lineage context and type of genomic alteration predict for the therapeutic relevance of tyrosine kinase inhibitors in human cancers
Authors: H. Vanacker, P.A. Cassier, M. Pérol, P. Saintigny, L. Eberst, M. Carbonnaux, M. Brahmi, L. Verlingue, I.L. Ray-Coquard, D. Pérol, J-Y Blay
Journal: Annals of Oncology (2019)
Poor Prognosis in Children with ABL-Class Fusion Positive B-Cell Acute Lymphoblastic Leukemia Treated According to AIEOP-BFM Protocols
Authors: Gunnar Cario, Veronica Leoni, Valentino Conter, Andishe Attarbaschi, Marketa Zaliova, Lucie Sramkova, Giovanni Cazzaniga, Grazia Fazio, Rosemary Sutton, Sarah Elitzur, Shai Izraeli, Melchior Lauten, Franco Locatelli, Giuseppe Basso, Barbara Buldini, Anke K Bergmann, Jana Lentes, Doris Steinemann, Gudrun Gohring, Brigitte Schlegelberger, Oskar A Haas, Denis Martin Schewe, Swantje Buchmann, Anja Moericke, Deborah L. White, Tamas Revesz, Martin Stanulla, Georg Mann, Nicole Bodmer, Nira Arad-Cohen, Jan Zuna, Maria Grazia Valsecchi, Martin Zimmermann, Martin Schrappe, Andrea Biondi
Journal: Blood (2019)
Association of Physician Characteristics With Perceptions and Experiences of Gender Equity in an Academic Internal Medicine Department
Authors: Shannon M. Ruzycki, Georgina Freeman, Aleem Bharwani, Allison Brown
Journal: JAMA Network Open (2019)

The persistence of inequities that disadvantage women physicians remains empirically underexplained. Understanding the cultural factors that are associated with disparities in harassment, discrimination, remuneration, and career trajectory are critical to addressing inequities.To explore how physicians perceive the climate for women physicians and compare perceptions and experiences of gender inequity among physicians based on characteristics including gender, faculty status, parental status, and years in practice.This sequential, explanatory, mixed-methods qualitative study used the Culture Conducive to Women's Academic Success (CCWAS; range 45-225, with higher scores indicating better perceived culture toward women), followed by individual semistructured interviews with physicians at the Department of Medicine of the University of Calgary. All 389 physician members of the Department of Medicine, including academic and clinical physicians and those of any gender, were invited to participate in the survey and interview phases.The culture within the department for women physicians was assessed using the CCWAS score. Scores were compared between respondents' gender and years in practice. Interviews with physicians were used to further explore findings from the CCWAS and to understand experiences and perceptions of gender disparities.A total of 169 of 389 physicians completed the survey (response rate, 43.4%; 102 [59.9%] women; 65 [38.9%] men; and 2 [1.2%] who did not disclose gender); 28 participants (7.2%) elected to participate in an interview (22 [78.6%] women; 6 [21.4%] men). Women physicians perceived the culture of the department toward women as significantly worse than men physicians (median [interquartile range] CCWAS score, 137.0 [118.0-155.0] vs 164.5 [154.0-183.4]; P < .001). Physicians with more than 15 years in practice perceived the culture toward women as significantly more favorable than physicians with 15 years or less in practice (median [interquartile range] CCWAS score, 157.0 [138.8-181.3] vs 147.0 [127.5-164.3]; P = .02). Qualitative data demonstrated that experiences of junior women (ie, physicians who graduated medical school after 1996, when an equal number of men and women in medical school was achieved in Canada) and perceptions of senior men (ie, those who graduated before 1996) were most different; junior women reported high rates of discrimination and harassment, while senior men perceived that the Department of Medicine had achieved gender equity.In this study, senior men physicians' perceptions of gender equity were different from lived experiences of gender inequity reported by junior women physicians. This demographic mismatch between perceptions and experiences of gender equity in medicine may explain the lack of action by leaders and decision-makers in medicine to mitigate disparities.
NCMP-11. THE CANCER AND COGNITION CLINIC AT WAKE FOREST BAPTIST HOSPITAL: SATISFYING AN UNMET NEED
Authors: Tiffany Cummings, Abigail Giles, Mary Liberatore, Adrian Laxton, Annette Carter, Stephen Tatter, Michael Chan, Glenn Lesser, Roy Strowd, Christina Cramer
Journal: Neuro-Oncology (2019)

Abstract Preservation of cognitive functioning is a top priority for brain tumor patients but is often not addressed in a systematic manner. To address this unmet need, we established a virtual neurocognitive clinic within our brain tumor center. The aim was to incorporate standardized neuropsychological examinations into routine care. To make neuropsychological testing achievable for patients with primary brain tumors, we developed a one-hour battery to measure core cognitive functions. We established a process where patients are offered cognitive testing at initial consult by neuro-oncology or radiation oncology. To reduce the burden of an extra appointment, patients are seen by neuropsychology in the Cancer Center (as opposed to the main hospital). Appointments are coordinated on the same day as other essential visits. Results are reviewed in multidisciplinary tumor boards. When possible, patients are seen for serial cognitive assessments at 3, 6 and 12 months after RT treatment. Providers in neuro-oncology, neurosurgery, and radiation oncology were encouraged to refer survivors to neuropsychology. After the clinic launch in 2017, 143 brain tumor patients were referred to neuropsychology. Prior to the clinic launch, 22 referrals were made over a comparable timeframe. Cognitive deficits were identified in most patients. After testing, patients received education on the brain-function relationship pertaining to their deficits. The patients’ referring provider received a full report containing recommendations for interventions based on testing outcomes 11 of the 38 patients who underwent pre-treatment assessments underwent testing 6 months post-RT. With the recent addition of a dedicated clinical coordinator, the rate of successful post-treatment cognitive evaluation is increasing. The cognitive, emotional, behavioral, and psychosocial impact of a brain tumor can be difficult to categorize and treat without formal evaluation. Integrating neuropsychological examination into routine care has resulted in a massive increase in the number of brain tumor patients getting a neuropsychologic assessment.
IMMU-47. RNA-NANOPARTICLE VACCINES ARE SAFE AND IMMUNOLOGICALLY ACTIVE IN CLIENT-OWNED CANINES WITH TERMINAL GLIOMAS
Authors: Sheila Carrera-Justiz, Brian Stover, Rowan Milner, Frances Weidert, Jianping Huang, Duane Mitchell, Hector Mendez-Gomez, Elias Sayour
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND The lack of appropriate preclinical murine glioblastoma models limits comprehensive toxicity/efficacy evaluation of investigational agents. To overcome this challenge, we evaluated the safety and activity of a new immunotherapeutic technology that we have pioneered (composed of tumor mRNA complexed into a custom lipid-nanoparticle formulation) in client-owned canines (pet dogs) diagnosed with malignant gliomas. OBJECTIVE/ METHODS Canine malignant gliomas were biopsied for generation of personalized tumor mRNA loaded into our custom lipid-nanoparticle (NP) vector. The patients received RNA-NPs intravenously beginning two weeks after their biopsy once weekly (x3) and no other anti-tumor therapeutic interventions. RESULTS Within a few hours after administration, tumor specific RNA-NPs elicited margination of peripheral blood mononuclear cells, which increased in the subsequent days/weeks post-treatment; suggesting that RNA-NPs mediate lymphoid honing of immune cell populations before egress. RNA-NPs also elicited increased: 1) serum interferon-α that spiked at 2 hours; 2) CD80 and MHCII on CD11c+ cells (demonstrating activation of peripheral DCs); and 3) interferon-γ + T-cells (i.e. activated T-cells). After receiving weekly RNA-NPs (×3), the canines had a steady course. Aside from low-grade fevers on the vaccination days, personalized tumor RNA-NPs (1x) were well tolerated with stable blood counts, chemistries, and renal/liver function tests. All patients assessed developed immunologic response with pseudoprogression or stable/smaller tumors by MRI. Although we have treated a small cohort, we have observed improvement in median/overall survival in all canine patients with terminal gliomas receiving RNA-NPs (compared with historical controls). CONCLUSION RNA-NPs were feasible, safe and immunologically active in client-owned canines with terminal gliomas. We have not appreciated significant toxicities in canines that would preclude investigation in humans at 1x dosing. Although these results need to be validated in larger canine data sets, these results suggest safety and activity of tumor specific RNA-NPs in canines with terminal gliomas.
Psychiatry and the Law
Authors: H. M. Holden
Journal: BMJ (1963)

the hope of severing a partly cut off tissue or by cutting the tube and allowing the trapped specimen to slough off so that eventually the capsule may be recovered in the faeces.With the tubes designed by Brandborg et al. and our- selves the knife movements are controlled at all times by the pull-wire, and thus any nipped mucosa can be released without trouble.To summarize, we believe that a smaller biopsy aperture, carefully con- trolled use of negative pressure, and indirect control of the movements of the knife make for safe biopsies.With our own child's-size biopsy tube no complications were encountered in 104 successful child biopsies.The investigator has therefore to choose between safety on the one hand, and simplicity of method and perhaps technical superiority on the other hand.Small intestinal biopsy in children must be regarded as a specialized procedure and requires skill and knowledge of tech- nique, whatever method is used.We believe that the pull-wire tubes should not be discarded in favour of the Crosby- Kugler tube, especially in paediatric work.They could certainly be improved technically.Would any paediatrician be interested in trying ?-I am, etc.,
Cell/molecular biology posters 336-351
Authors: S Parry, J Barton, M Welfare, I Mohammed, L Cherkas, S Riley, T Spector, N Trudgill, S Lal, J Mclaughlin, G Giampaolo, G Dockray, A Varro, D Thompson, J Jones, D Kendall, P Millns, C Hawkey, S Dunlop, D Jenkins, R Spiller, L Gregory, L Yaguez, S Coen, E Amaro, S Smale, A Hobson, S Williams, Q Aziz, V Chudleigh, E Brennan, S Tarry, S Myers, S Lewis, G Smith, K Palmer
Journal: Gut (2002)

Introduction: Previous studies, many uncontrolled, suggest 4 to 32% of people develop irritable bowel syndrome (IBS) after ID.Little information is available on the development of other FGIDs after ID.Aim: To determine if patients with stool culture confirmed bacterial diarrhoea were more likely to develop gut symptoms consistent with a diagnosis of IBS, functional dyspepsia or functional diarrhoea at 3 and 6 month follow up compared with community controls.Methods: A prospective community-based case-control study over one year.Subjects with stool positive bacterial infectious diarrhoea and control subjects from the same primary care practice were invited to participate.The presence or not of IBS, functional dyspepsia or functional diarrhoea was diagnosed at the start and at follow up using self-complete Rome II modular questionnaires.The diagnosis of a baseline FGID excluded subjects from continuing.There were 128 cases and 219 community controls eligible and who consented to participate.Results: At follow up there was a higher incidence of FGIDs in the cases compared with controls, mainly due to a higher incidence of IBS (see table ).There was no difference in the incidence of functional dyspepsia between cases and controls.Conclusions: IBS and functional diarrhoea is diagnosed more frequently in people at three and six-month follow up after an episode of stool positive bacterial diarrhoea compared with community controls despite careful exclusion of people with pre-existing FGIDS and adds further support for the concept of post-infectious IBS.
CC-92480, a Novel Cereblon E3 Ligase Modulator, Is Synergistic with Dexamethasone, Bortezomib, and Daratumumab in Multiple Myeloma
Authors: Lilly Wong, Rama Krishna Narla, Jim Leisten, Daniel Bauer, Matthew Groza, Bonny Gaffney, Courtney G. Havens, Justin Choi, Jack Houston, Antonia Lopez-Girona, Joshua Hansen, Brian E. Cathers, James Carmichael, Daniel W. Pierce
Journal: Blood (2019)
Post-operative Position
Authors: H. K. Ashworth
Journal: BMJ (1958)

<h3>ABSTRACT</h3> Gausemycins A and B are the first members of the novel lipoglycopeptides family produced by <i>Streptomyces roseoflavus</i> INA-Ac-5812, which showed the ability to fight clinically important Gram-positive bacteria, including methicillin-resistant <i>Staphylococcus aureus</i>. However, new antibiotics need to be studied in depth to determine their full potential. In this study, we concentrated our efforts to investigate resistance emerging within <i>S. aureus</i> upon gausemycin A application. Using serial passaging of <i>S. aureus</i> FDA209P in increasing concentrations of gausemycin A, we obtained the resistant variant <i>S. aureus</i> 5812R which are 80-times more resistant comparing to the origin strain. Moreover, obtained resistance is stable, since 15 passages in a drug-free medium did not restore bacterial susceptibility to gausemycin A. Elucidating of the differences between resistant and parent strains was concerned antibiotic cross-resistance, structure of bacterial membrane, and response at genetic level. Susceptibility testing of <i>S. aureus</i> 5812R revealed the acquisition of cross-resistance to daptomycin, cefazolin, and tetracycline, while resistance to vancomycin, nisin and ramoplanin absence. The composition of fatty acids constituting the cytoplasmic membrane of <i>S. aureus</i> 5812R, was represented by increased content of <i>anteiso</i>- branched chain fatty acids, while <i>iso</i>-branched chain fatty acids was decreased comparing the origin <i>S. aureus</i> FDA209P strain. The relative expression of the <i>cls</i> gene catalyzing the synthesis of cardiolipin in the resistant cells was higher compared to the <i>S. aureus</i> FDA209P.
NRF2 Is Targeted By the Polyphenol Quercetin and Induces Apoptosis, in Part, through up Regulation of Pro Apoptotic Mirs
Authors: Marisa Claudia Alvarez De Prax, Karla P.V Ferro, Irene Santos, Cristiane Okuda Torello, Myriam Salazar-Terreros, Sara T Olalla Saad
Journal: Blood (2019)
Phase 1 Study of on Site Manufactured Anti-CD19 CAR-T Cells: Responses in Subjects with Rapidly Progressive Refractory Lymphomas
Authors: Paolo F Caimi, Jane Reese, Folashade Otegbeye, Dina Schneider, Kristen Bakalarz, Kirsten M Boughan, Brenda Cooper, Molly M Gallogly, Erin Galloway, Winfried Kruger, Andrew Worden, Michael Kadan, Filipa Blasco Lopes, Ashish Sharma, Ehsan Malek, Leland Metheny, Seema Patel, Benjamin K. Tomlinson, David Wald, Rafick-Pierre Sekaly, Rimas Orentas, Boro Dropulic, Marcos de Lima
Journal: Blood (2019)
Study records improved blood flow within a month of replacing cigarettes with vaping
Authors: Nigel Hawkes
Journal: BMJ (2019)

Switching from cigarettes to an electronic equivalent has prompt and significant benefits on vascular function, a randomised trial has shown.1

A month after switching, participants in the trial had gone a long way towards restoring the ability of their arteries to dilate, a key measure of blood vessel health. Women showed greater benefits than men.

The trial was carried out in Dundee in Scotland and is believed to be the largest so far conducted. Many previous studies of e-cigarettes have been based on a handful of participants, but the Dundee trialists managed to recruit 114 long term smokers who had smoked at least 15 cigarettes a day for at least two years.

They were divided into three groups. Those who did not wish to quit continued smoking, while those who wanted to quit were randomised to either e-cigarettes containing …
Fibg390-396A Limits Metastatic Potential Via a Mechanism Independent of Fibrin-Myeloid Cell Interactions, but Prospectively through the Disruption of FXIII-Mediated Fibrin Crosslinking
Authors: Brenton J Francisco, Balkrishan Sharma, Leah A. Rosenfeldt, Duaa Mureb, Joseph S. Palumbo
Journal: Blood (2019)
An Update of Australasian Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in the Molecular Era
Authors: Yadanar Lwin, Simon Zhao-Xiong He, Andrew Spencer, Duncan Purtill, Ashley Mcewan, Peter Browett, Andrew Butler, John Carter, Peter G Bardy, Glen A Kennedy, Jeffrey Szer, David Ritchie, Matthew Greenwood, Stephen R Larsen, Sam Milliken, Hock Choong Lai, David Gottlieb, John Kwan, Donna Aarons, Steven Tran, Nada Hamad
Journal: Blood (2019)
DNMT3Awt NPM1-Mutation Defines a Subgroup of MDS with Special Favorable Outcomes Towards Decitabine Therapy
Authors: Lingyun Wu, Xiao Li, Feng Xu, He Qi, Zheng Zhang, Dong Wu, Luxi Song, Liyu Zhou, Chao Xiao, Jiying Su, Juan Guo, Chunkang Chang
Journal: Blood (2019)
Glycosylationof Immunoglobulins Determine Bone Loss in Multiple Myeloma
Authors: Marita Westhrin, Vlado Kovcic, Albert Bondt, Stephanie Holst, Zejian Zhang, Anders Sundan, Tobias S. Slørdahl, Anders Waage, Manfred Wuhrer, Therese Standal
Journal: Blood (2019)
Targeting the FMS-like Tyrosin Kinase 3 with the Unicar System: Preclinical Comparison of Murine and Humanized Single-Chain Variable Fragment-Based Targeting Modules
Authors: Frederick Fasslrinner, Claudia Arndt, Anja Feldmann, Stefanie Koristka, Liliana Raquel Loureiro, Marc Schmitz, Gundram Jung, Martin Bornhaeuser, Michael Bachmann
Journal: Blood (2019)
Phase I trial of metronomic oral topotecan in combination with pazopanib utilizing a daily dosing schedule to treat recurrent or persistent gynecologic tumors.
Authors: Todd D. Tillmanns, Mark E. Reed, Melissa C. Privett, Amanda L. Johns, Mark S. Walker, Arthur C. Houts
Journal: Journal of Clinical Oncology (2012)

5014 Background: Metronomic oral topotecan has antiangiogenic properties. Oral pazopanib is also a potent inhibitor of VEGF angiogenesis with clinical benefit. This study investigated the safety and efficacy of daily topotecan and pazopanib. Methods: This phase I, single-center, open-label, dose ranging study comprised 28-day cycles of daily oral topotecan/pazopanib at dose levels of 0.50/400, 0.25/800, 0.25/600, and 0.25/400 mg. A standard 3+3 dose escalation design was used. Dose limiting toxicity (DLT) was defined as ≥ grade 3 adverse event (AE) occurring in cycle 1, noncompletion of cycle 1 at prescribed dose, or inability to start cycle 2 as scheduled due to toxicities. Imaging was conducted after every 2 cycles for response assessment. Confirmed responses were evaluated per RECIST 1.0. Results: 25 extensively pretreated patients (pts) with gynecologic tumors (6 cervical, 7 endometrial, 8 ovarian, 4 other) were enrolled. Mean age was 61 years; 19 Caucasian, 6 African American. Median number of cycles received was 4 (range 1-19). DLTs occurred ≥ 2 pts for A (2/6), B (2/7), C (3/7). For level D, 1/5 had a DLT, but one dose level C pt with a DLT received level D dosing due to unavailability of pazopanib. 9/25 pts had any serious adverse event (SAE), and respiratory SAEs were most common (4/16 SAEs). Nausea, fatigue, dysgeusia, diarrhea, and vomiting were the most common conditions reported as non-serious AEs. The Table shows best overall response (28%) by dose level. Conclusions: DLTs in dose levels C and D were effectively managed with minor dose and schedule adjustments. 4 pts with DLTs at these doses remained on treatment for 4, 5, and 6 months, with one pt still on treatment at 9 months. Given the initial biologically favorable signal in this heavily pretreated group and low toxicity, we recommend a randomized phase II trial to define efficacy using the 0.25/600 regimen allowing for dose reduction if needed. [Table: see text]
P1.12 Real World Characterization and Treatment Patterns of Patients with Thymic Carcinoma: Lessons from a Latin American Collaborative Study (CLICaP-LATimus)
Authors: L. Mas, A.K. Patane, O. Arrieta, T. Soria, A.F. Cardona, C. Martín, A. Ruiz-Patiño, R. Ruiz, P. Rioja, S. Lozano, L. Zatarain Barron, F. Barrón, M. Corassa, H. Freitas, V.C. Cordeiro De Lima, L. Corrales-Rodriguez, C. Sotelo, J. Rodríguez, L. Ricaurte, J. Ávila, D. Mayorga, M. Bravo, P. Archila, J. Otero, H. Carranza, C. Vargas, R. Rosell, J. Remon
Journal: Journal of Thoracic Oncology (2019)