tbuckley/cabot-search huggingface dataset:
A Phase I Study Combining CDK2/9 Inhibitor CYC065 with Venetoclax, a BCL2 Inhibitor, to Treat Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: William G. Wierda, Seung Tae Lee, Rong Chen, Daniella Zheleva, David Blake, Judy H Chiao, William Plunkett
Journal: Blood (2019)
NHS becomes political football as electioneering kicks off
Authors: Abi Rimmer, Gareth Iacobucci
Journal: BMJ (2019)

The UK election season kicked off last weekend amid what is already shaping up to be a hard fought match between the country’s two bitterest rivals. Almost immediately, NHS leaders called on politicians not to use the NHS as a “political football”—a familiar call during UK general elections.

But when the whistle blew, Labour immediately went on the attack against the Conservatives by revealing the results of a freedom of information request that they said showed a big increase in the number of cancelled operations. Between April 2018 and March 2019 a total of 78 981 elective and urgent operations in England were cancelled, the data showed—less than in 2017-18 (81 565) but more than in 2016-17 (74 170). Staffing problems and equipment failures were responsible for more than 15 000 cancelled operations last year, Labour said.

Perhaps sensing an …
Association of Sex With Postoperative Mortality Among Patients With Heart Failure Who Underwent Elective Noncardiac Operations
Authors: Aviva S. Mattingly, Benjamin J. Lerman, Rita Popat, Sherry M. Wren
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Sex differences in postoperative outcomes in patients with heart failure (HF) have not been well characterized. Women generally experience a lower postoperative mortality risk after noncardiac operations. It is unclear if this pattern holds among patients with HF. <h3>Objectives</h3> To determine if the risk of postoperative mortality is associated with sex among patients with HF who underwent noncardiac operations and to determine if sex is associated with the relationship between HF and postoperative mortality. <h3>Design, Setting, and Participants</h3> This multisite cohort study used data from the US Department of Veterans Affairs Surgical Quality Improvement Project database for all patients who underwent elective noncardiac operations from October 1, 2009, to September 30, 2016, with a minimum of 1 year follow-up. The data analysis was conducted from May 1, 2018, to August 31, 2018. <h3>Exposures</h3> Heart failure, left ventricular ejection fraction, and sex. <h3>Main Outcomes and Measures</h3> Postoperative mortality at 90 days. <h3>Results</h3> Among 609 735 patients who underwent elective noncardiac operations from 2009 to 2016, 47 997 patients had HF (7.9%; mean [SD] age, 68.6 [10.1] years; 1391 [2.9%] women) and 561 738 patients did not have HF (92.1%; mean [SD] age, 59.4 [13.4] years; 50 862 [9.1%] women). Among patients with HF, female sex was not independently associated with 90-day postoperative mortality (adjusted odds ratio [aOR], 0.97; 95% CI, 0.71-1.32). Although HF was associated with increased odds of postoperative mortality in both sexes compared with their peers without HF, the odds of postoperative mortality were higher among women with HF (aOR, 2.44; 95% CI, 1.73-3.45) than men with HF (aOR, 1.64; 95% CI, 1.54-1.74), suggesting that HF may negate the general protective association of female sex with postoperative mortality (<i>P</i>for interaction of HF × sex = .03). This pattern was consistent across all levels of left ventricular ejection fraction. <h3>Conclusions and Relevance</h3> Although HF was associated with increased odds of postoperative mortality in both sexes compared with their peers without HF, the odds of postoperative mortality were higher among women with HF than men with HF, suggesting that HF may negate the general protective association of female sex with postoperative mortality risk in noncardiac operations.
Appropriateness of Surgical Antimicrobial Prophylaxis Practices in Australia
Authors: Courtney Ierano, Karin Thursky, Caroline Marshall, Sonia Koning, Rod James, Sandra Johnson, Nabeel Imam, Leon J. Worth, Trisha Peel
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Surgical antimicrobial prophylaxis (SAP) is a common indication for antibiotic use in hospitals and is associated with high rates of inappropriateness. <h3>Objective</h3> To describe the SAP prescribing practices and assess hospital, surgical, and patient factors associated with appropriate SAP prescribing. <h3>Design, Setting, and Participants</h3> Multicenter, national, quality improvement study with retrospective analysis of data collected from Australian hospitals via Surgical National Antimicrobial Prescribing Survey audits from January 1, 2016, to June 30, 2018. Data were analyzed using multivariable logistic regression. Crude estimates of appropriateness were adjusted for factors included in the model by calculating estimated marginal means and presented as adjusted-appropriateness with 95% confidence intervals. <h3>Main Outcomes and Measures</h3> Adjusted appropriateness and factors associated with inappropriate prescriptions. <h3>Results</h3> A total of 9351 surgical episodes and 15 395 prescriptions (10 740 procedural and 4655 postprocedural) were analyzed. Crude appropriateness of total prescriptions was 48.7% (7492 prescriptions). The adjusted appropriateness of each surgical procedure group was low for procedural SAP, ranging from 33.7% (95% CI, 26.3%-41.2%) for dentoalveolar surgery to 68.9% (95% CI, 63.2%-74.5%) for neurosurgery. The adjusted appropriateness of postprocedural prescriptions was also low, ranging from 21.5% (95% CI, 13.4%-29.7%) for breast surgery to 58.7% (95% CI, 47.9%-69.4%) for ophthalmological procedures. The most common reason for inappropriate procedural SAP was incorrect timing (44.9%), while duration greater than 24 hours was the most common reason for inappropriate postprocedural SAP (54.3%). <h3>Conclusions and Relevance</h3> High rates of inappropriate procedural and postprocedural antimicrobial use were demonstrated across all surgical specialties. Reasons for inappropriateness, such as timing and duration, varied according to the type of SAP and surgical specialty. These findings highlight the need for improvement in SAP prescribing and suggest potential targeted areas for action.
Streamline - Study of Relapse or Refractory (R/R) FLT3-Mutated Acute Myeloid Leukemia (AML) Using Electronic Medical Records (EMR): First Analysis from a Multicenter, Retrospective Cohort Study
Authors: Amer M. Zeidan, Adrienne Gilligan, Santosh Gautam, Nan Hu, David L. Grinblatt, Bhavik J. Pandya
Journal: Blood (2019)
Analysis of 129 Myeloablative Double-Unit Cord Blood Transplantation Recipients Demonstrates an Independent Association Between Non-Dominant Unit TNC Dose and Engraftment Suggesting a Facilitation Effect
Authors: Duncan Purtill, Marissa N Lubin, Doris M. Ponce, Sergio Giralt, Miguel-Angel Perales, Richard J O'Reilly, Marcel Van Den Brink, James W. Young, Andromachi Scaradavou, Cladd Stevens, Juliet N. Barker
Journal: Blood (2014)
The 2017 European Leukemianet Genetic Risk Classification Performs Poorly in Older Patients with Acute Myeloid Leukemia (AML) and Should be Refined to Identify Patients Requiring Additional or Alternative Treatment
Authors: Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Deedra Nicolet, Alice S. Mims, Dimitrios Papaioannou, Christopher J. Walker, James S. Blachly, Sophia E. Maharry, Andrew J. Carroll, Richard M. Stone, Bayard L Powell, Albert de la Chapelle, Eunice S. Wang, Jonathan E. Kolitz, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2019)
Peak Lymphocyte Count after CAR T Infusion Is a Clinically Accessible Test That Correlates with Clinical Response in Axicabtagene Ciloleucel Therapy for Lymphoma
Authors: Mattia Novo, M Hasib Sidiqi, Jonas Paludo, Sangeetha Gandhi, Jilan Kubusek, Tuan Truong, Justin Hayne, Stephen M Ansell, N. Nora Bennani, Jose C Villasboas, Adrienne Nedved, Gina Lange, Eva Brandes, Hassan B. Alkhateeb, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Saad S. Kenderian, Taxiarchis Kourelis, Shaji K. Kumar, Mithun Vinod Shah, Mustaqeem Siddiqui, Rahma M Warsame, Patrick Johnston, Yi Lin
Journal: Blood (2019)
TMIC-60. COMPREHENSIVE SPATIAL CHARACTERIZATION OF IMMUNE CELLS IN THE CNS BRAIN TUMOR MICROENVIRONMENT
Authors: Cynthia Kassab, Daniel Zamler, Pravesh Gupta, Visish Srinivasan, Ganesh Rao, Sujit Prabhu, Jason Huse, Greg Fuller, Janet Bruner, Lauren Langford, Ian McCutcheon, Sherise Ferguson, Jeffrey Weinberg, Ignacio Wistuba, Frederick Lang, Krishna Bhat, Amy Heimberger
Journal: Neuro-Oncology (2019)

Abstract Previous immune profiling in brain tumors has mostly focused on the high-density tumor areas, and as such, little is known about the nature and types of immunological responses that occur across the tumor landscape, including at the tumor-central nervous system (CNS) interface. En bloc resections of glioblastomas (n=10) and CNS lung metastases (n=10) were oriented on slides as whole mount wedges spanning three anatomical areas including the invasive edge, tumor region, and necrotic core. Tumor segmentation was performed and regional differences were immunologically analyzed for 770 immune genes using the NanoString nCounter System with CIBERSORT analysis to delineate immune gene signatures. The analysis was validated using multiplex immunohistochemistry (IHC). The top upregulated immune genes in the GBM necrotic core were associated with macrophages, including the CD163 lineage marker, chemotactic factors (such as CCL18 and SAA1), and the phagocytosis stimulatory factors (such as IL-8 and MARCO). The necrotic core downregulates GBM antigens (such as IL13RA2 and MAGEB2), markers of dendritic cells (such as LILRA4), and immune stimulatory processes including MHC, IFN, IL-12, TNF, and ICOS expression. In direct contrast, the infiltrating edge of the GBM relative to the tumor is enriched with stimulators for NK cytotoxicity (i.e., CD244, the fractalkine receptor for immune cells), chemokines for thymocytes and dendritic cells, and immune stimulatory IL-12 receptors. Glioblastoma has rare focal isolated areas of CD3 T-cell reactivity within the tumor. Similar to GBM, the necrotic center of lung metastases is enriched in immune suppressive macrophages, as reflected by CD163 IHC staining and arginase expression; however, they are more frequently infiltrated with M1 macrophages. Yet the majority of lung cancers are more diffusely infiltrated with CD3 T cells, especially at the infiltrating edge. In general, we noted distinct inter- and intratumoral immune gene signatures, with macrophages dominating the brain tumors, especially the necrotic core.
Patients with Lymphoplasmacytic Lymphoma Can Be Salvaged with Autologous Stem Cell Transplantation, Irrespectively of the Number of Previous Treatment Lines. Analysis of 146 Cases from the European Bone Marrow Transplant Registry (EBMT).
Authors: Charalampia A. Kyriakou, Anthony H. Goldstone, Anna Sureda, Kwee Yong, Shirley D’Sa, Goli Taghipour, Carmen Ruiz de Elvira, David C. Linch, Norbert Schmitz
Journal: Blood (2004)
Echocardiographic Changes with Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome. Long-Term Pickwick Randomized Controlled Clinical Trial
Authors: Juan F. Masa, Babak Mokhlesi, Iván Benítez, Maria Victoria Mogollon, Francisco Javier Gomez de Terreros, Maria Ángeles Sánchez-Quiroga, Auxiliadora Romero, Candela Caballero-Eraso, Maria Luz Alonso-Álvarez, Estrella Ordax-Carbajo, Teresa Gomez-Garcia, Mónica González, Soledad López-Martín, José M. Marin, Sergi Martí, Trinidad Díaz-Cambriles, Eusebi Chiner, Carlos Egea, Javier Barca, Francisco-José Vázquez-Polo, Miguel A. Negrín, María Martel-Escobar, Ferran Barbe, Jaime Corral, Agustin Sojo, Nicolás González-Mangado, Maria F. Troncoso, Maria-Ángeles Martinez-Martinez, Elena Ojeda-Castillejo, Daniel López Padilla, Santiago J. Carrizo, Begoña Gallego, Mercedes Pallero, Odile Romero, Maria Antonia Ramón, Eva Arias, Jesús Muñoz-Méndez, Cristina Senent, Jose N. Sancho-Chust, Nieves Belén Navarro Soriano, Emilia Barrot, José M. Benítez, Jesús Sanchez-Gómez, Rafael Golpe, María Antonia Gómez Mendieta, Silvia Gomez, Mónica Bengoa
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Obesity hypoventilation syndrome (OHS) has been associated with cardiac dysfunction. However, randomized trials assessing the impact of long-term noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) on cardiac structure and function assessed by echocardiography are lacking.Objectives: In a prespecified secondary analysis of the largest multicenter randomized controlled trial of OHS (Pickwick Project; N = 221 patients with OHS and coexistent severe obstructive sleep apnea), we compared the effectiveness of three years of NIV and CPAP on structural and functional echocardiographic changes.Methods: At baseline and annually during three sequential years, patients underwent transthoracic two-dimensional and Doppler echocardiography. Echocardiographers at each site were blinded to the treatment allocation. Statistical analysis was performed using a linear mixed-effects model with a treatment group and repeated measures interaction to determine the differential effect between CPAP and NIV.Measurements and Main Results: A total of 196 patients were analyzed: 102 were treated with CPAP and 94 were treated with NIV. Systolic pulmonary artery pressure decreased from 40.5 ± 1.47 mm Hg at baseline to 35.3 ± 1.33 mm Hg at three years with CPAP, and from 41.5 ± 1.56 mm Hg to 35.5 ± 1.42 with NIV (P < 0.0001 for longitudinal intragroup changes for both treatment arms). However, there were no significant differences between groups. NIV and CPAP therapies similarly improved left ventricular diastolic dysfunction and reduced left atrial diameter. Both NIV and CPAP improved respiratory function and dyspnea.Conclusions: In patients with OHS who have concomitant severe obstructive sleep apnea, long-term treatment with NIV and CPAP led to similar degrees of improvement in pulmonary hypertension and left ventricular diastolic dysfunction.Clinical trial registered with www.clinicaltrials.gov (NCT01405976).
RTHP-14. PSEUDOPROGRESSION IN HIGH GRADE GLIOMA PATIENTS AFTER PROTON OR PHOTON THERAPY
Authors: Vonetta Williams, Lia Halasz, Jason Rockhill, James Fink
Journal: Neuro-Oncology (2019)

Abstract Pseudoprogression is defined as the appearance of false progression on MR imaging following radiation therapy. Proton therapy is thought to have increased relative biological effectiveness-the ratio of the doses required by two types of radiation to cause the same level of effect-near the edges of the high dose volume. This could lead to different rates of pseudoprogression for protons compared to photons. In our IRB approved study, a board-certified neuroradiologist reviewed serial imaging of 74 patients (photons: n=37, protons: n=37) treated from 2013–2018 with either proton or photon radiotherapy to 59.4–60 Gy in 30–33 fractions and temozolomide for high grade glioma. MR imaging was performed 1 month after completion of treatment and then every 3 months. True progression was scored based on updated RANO criteria. Pseudoprogression was determined if imaging improved without change in therapy. Cumulative incidences of these outcomes and survival were calculated utilizing Kaplan-Meier analyses. Patient and treatment factors were analyzed for their association with incidence of pseudoprogression. Median follow-up for alive patients in the proton and photon groups were 15 and 29 months, respectively. Median age was 49 years in the proton group and 54 years in the photon group (p=0.17). Among proton patients, 14 had grade III glioma and 23 had grade IV glioblastoma. Among photon patients, 1 had grade III glioma. Median survival was 23 and 35 months for the proton and photon groups, respectively (p=0.57). The cumulative incidence of pseudoprogression was 14.4% and 10.4% at 12 months for the proton and photon groups, respectively (p=0.53). Grade, extent of resection, age, and IDH status, were not significantly associated with development of pseudoprogression. MGMT methylated tumors showed a trend toward association with pseudoprogression compared to unmethylated tumors (p=0.058). We concluded that the incidence of pseudoprogression is similar regardless of whether proton or photon therapy was utilized.
Dreamm-3: A Phase 3, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin (GSK2857916) Monotherapy Compared with Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Participants with Relapsed/Refractory Multiple Myeloma (RRMM)
Authors: Katja Weisel, Thomas G Hopkins, Doug Fecteau, Weichao Bao, Corinne Quigley, Roxanne C Jewell, Maureen Nichols, Joanna Opalinska
Journal: Blood (2019)
Helen Salisbury: The performance of kindness
Authors: Helen Salisbury
Journal: BMJ (2019)

Patients arrive at a GP appointment with all manner of symptoms and varying degrees of unease, anxiety, pain, and fear. If we aim for patients to leave feeling better than when they came, they need to know that they’ve been taken seriously and that their concerns have been explored and understood. They need to trust in the competence of the doctor and be able to rely on our kindness and empathy, even if practical solutions to their problems are in short supply.

Most of the time this isn’t too hard—I have …
Antimicrobial central venous catheters do not reduce infections in pre-term babies
Authors: Rob Cook, Duncan Fortescue-Webb, Rosie Martin
Journal: BMJ (2019)

The study Gilbert R, Brown M, Rainford N et al. Antimicrobial-impregnated central venous catheters for prevention of neonatal bloodstream infection (PREVAIL): an open-label, parallel-group, pragmatic, randomised controlled trial. Lancet Child Adolesc Health 2019;3:381-90. The study was funded by the NIHR Health Technology Assessment programme (project number 12/167/02). To read the full NIHR Signal, go to https://discover.dc.nihr.ac.uk/content/signal-000782/antimicrobial-central-venous-catheters-for-pre-term-babies-do-not-reduce-infections
Quinidine-induced Syncope
Authors: P. B. Halmos
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.,
TMOD-25. GLIOBLASTOMA ORGANOIDS: A MODEL SYSTEM FOR PATIENT-SPECIFIC THERAPEUTIC TESTING
Authors: Ryan Salinas, Daniel Zhang, Fadi Jacob, Phuong Nguyen, Saad Sheikh, Stefan Prokop, Jay Dorsey, MacLean Nasrallah, Steven Brem, Donald O’Rourke, Guo-li Ming, Hongjun Song
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma treatment options remain limited due to its aggressive and invasive nature. It is increasingly appreciated that molecular heterogeneity between tumors and within tumors likely contributes to the lack of therapeutic advances. To maintain the inherent heterogeneity of glioblastoma, we employed a novel method to rapidly culture glioblastoma organoids (GBOs) directly from neurosurgical resection. GBOs are routinely generated around two weeks following initial resection. Comprehensive histologic and sequencing analyses demonstrated similarity to primary tumors. Leveraging clinical molecular and sequencing data, selected GBOs were treated with radiation/temozolamide and targeted inhibitor therapies. The effect on proliferation was measured by the percentage of KI67+ cells and gene set enrichment (GSEA) analysis was performed to compare the pre-treated expression signature amongst responsive and non-responsive tumors. Treatment of organoids with radiation/temozolamide led to a decrease in the percentage of KI67+ cells in four of eight patient-derived organoid lines with some evidence of correlative radiographic response Gene sets associated with radiation response and TNF signaling were enriched in radiation/temozolamide sensitive GBOs. GBO response to EGFR inhibition via gefitinib treatment was specific to EGFR altered tumors, whose expression also enriched for EGF signaling pathway expression. Two GBOs had downstream NF1 mutations that responded to the MEK inhibitor trametinib. On GSEA, gene expression of NF1 mutated GBOs enriched for RAS signaling. One GBO line was found to have a PI3K mutation and responded dramatically to mTOR inhibition via everolimus. Dichotomous efficacy of MEK and mTOR inhibition was also noted by tumor-specific changes in GBO diameter following treatment. This novel culturing method of GBOs maintains intertumoral and intratumoral heterogeneity and allows for therapeutic testing within two weeks of neurosurgical resection. As clinical sequencing because increasingly prevalent, GBOs may become a valuable tool to functionally test mutation-specific treatment strategies in a patient-specific manner within a clinically relevant time frame.
P1.06 Determination of Exposure to Tobacco Smoke and the Percentage of Global DNA Methylation in Smokers and Patients with Lung Cancer
Authors: A.G. Alcázar-Ramos, M.A. Meraz-Ríos, M.D.P. Figueroa-Corona, D.G. García-Gutiérrez, A.D. Bertadillo-Jilote, I.F. Pérez-Ramírez, K.L. García-Mejía, B. Ugalde-Villanueva, K.I. Lira-De León
Journal: Journal of Thoracic Oncology (2019)
Development of a Novel Deep Transfer Learning Framework to Characterize Inter- and Intra-Tumor Heterogeneity in Myeloma Patients
Authors: Travis S Johnson, Christina Y Yu, Chuanpeng Dong, Tongxin Wang, Mohammad Issam Abu Zaid, Rafat Abonour, G. David Roodman, Yunlong Liu, Kun Huang
Journal: Blood (2019)
Prediction of High-Risk Group of Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Patients Using a CT-Based Radiomics Model with Machine Learning
Authors: Raoul Santiago, Johanna Ortiz Jimenez, Reza Forghani, Nikesh Muthukrishnan, Olivier Del Corpo, Shairabi Karthigesu, Muhammad Yahya Haider, Caroline Reinhold, Sarit Assouline
Journal: Blood (2019)