tbuckley/cabot-search huggingface dataset:
Cost-Effectiveness of Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer
Authors: Bin Wu, Lizheng Shi
Journal: Journal of the National Comprehensive Cancer Network (2020)

Maintenance therapy with the PARP inhibitor olaparib for metastatic pancreatic cancer (MPC) with a germline BRCA1 or BRCA2 mutation has been shown to be effective. We aimed to evaluate the cost-effectiveness of maintenance olaparib for MPC from the US payer perspective.A partitioned survival model was adopted to project the disease course of MPC. Efficacy and toxicity data were gathered from the Pancreas Cancer Olaparib Ongoing (POLO) trial. Transition probabilities were estimated from the reported survival probabilities in each POLO group. Cost and health preference data were derived from the literature. The incremental cost-utility ratio, incremental net-health benefit, and incremental monetary benefit were measured. Subgroup analysis, one-way analysis, and probabilistic sensitivity analysis were performed to explore the model uncertainties.Maintenance olaparib had an incremental cost-utility ratio of $191,596 per additional progression-free survival (PFS) quality-adjusted life-year (QALY) gained, with a high cost of $132,287 and 0.691 PFS QALY gained, compared with results for a placebo. Subgroup analysis indicated that maintenance olaparib achieved at least a 16.8% probability of cost-effectiveness at the threshold of $200,000/QALY. One-way sensitivity analyses revealed that the results were sensitive to the hazard ratio of PFS and the cost of olaparib. When overall survival was considered, maintenance olaparib had an incremental cost-utility ratio of $265,290 per additional QALY gained, with a high cost of $128,266 and 0.483 QALY gained, compared with results for a placebo.Maintenance olaparib is potentially cost-effective compared with placebo for patients with a germline BRCA mutation and MPC. Economic outcomes could be improved by tailoring treatment based on individual patient factors.
Characterization of T-ALL-Specific Heterogenous Blast Populations Using High Resolution Single Cell Profiling
Authors: Swati S Bhasin, Ryan J Summers, Beena E Thomas, Debasree Sarkar, Bhakti Dwivedi, Sunita I Park, Deborah DeRyckere, Sharon M. Castellino, Manoj Bhasin, Douglas K Graham
Journal: Blood (2020)
Updates from Ongoing, First-in-Human Phase 1 Dose Escalation and Expansion Study of TTI-621, a Novel Biologic Targeting CD47, in Patients with Relapsed or Refractory Hematologic Malignancies
Authors: Steven M. Horwitz, James M. Foran, Michael Maris, Ahmed Sawas, Craig Okada, Tatyana A. Feldman, Mark D. Minden, Lubomir Sokol, Matthew Mei, Ian W. Flinn, Diego Villa, Mary-Elizabeth M. Percival, Deepa Jagadeesh, Kerry J. Savage, Oleg E. Akilov, Catherine Diefenbach, Youn H. Kim, Gloria H. Y. Lin, Tina Catalano, Penka S. Petrova, Bob Uger, Naomi Molloy, Kathleen Large, Yaping Shou, Stephen M. Ansell
Journal: Blood (2020)
Association Between Surgical Technical Skill and Long-term Survival for Colon Cancer
Authors: Brian C. Brajcich, Jonah J. Stulberg, Bryan E. Palis, Jeanette W. Chung, Reiping Huang, Heidi Nelson, Karl Y. Bilimoria
Journal: JAMA Oncology (2020)

Association Between Surgical Technical Skill and Long-term Survival for Colon CancerSurgical technique is presumed to be an important determinant of patient outcomes.Surgical technical skill, measured by video review, has been associated with postoperative morbidity and histopathologic outcomes. 1-3However, it is unknown whether technical skill is associated with long-term survival.Our objective was to assess the association between surgical technical skill and overall survival following colectomy for colon cancer.
US Clinicians’ Experiences and Perspectives on Resource Limitation and Patient Care During the COVID-19 Pandemic
Authors: Catherine R. Butler, Susan P. Y. Wong, Aaron G. Wightman, Ann M. O’Hare
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Little is known about how US clinicians have responded to resource limitation during the coronavirus disease 2019 (COVID-19) pandemic. <h3>Objective</h3> To describe the perspectives and experiences of clinicians involved in institutional planning for resource limitation and/or patient care during the pandemic. <h3>Design, Setting, and Participants</h3> This qualitative study used inductive thematic analysis of semistructured interviews conducted in April and May 2020 with a national group of clinicians (eg, intensivists, nephrologists, nurses) involved in institutional planning and/or clinical care during the COVID-19 pandemic across the United States. <h3>Main Outcomes and Measures</h3> Emergent themes describing clinicians' experience providing care in settings of resource limitation. <h3>Results</h3> The 61 participants (mean [SD] age, 46 [11] years; 38 [63%] women) included in this study were practicing in 15 US states and were more heavily sampled from areas with the highest rates of COVID-19 infection at the time of interviews (ie, Seattle, New York City, New Orleans). Most participants were White individuals (39 [65%]), were attending physicians (45 [75%]), and were practicing in large academic centers (≥300 beds, 51 [85%]; academic centers, 46 [77%]). Three overlapping and interrelated themes emerged from qualitative analysis, as follows: (1) planning for crisis capacity, (2) adapting to resource limitation, and (3) multiple unprecedented barriers to care delivery. Clinician leaders worked within their institutions to plan a systematic approach for fair allocation of limited resources in crisis settings so that frontline clinicians would not have to make rationing decisions at the bedside. However, even before a declaration of crisis capacity, clinicians encountered varied and sometimes unanticipated forms of resource limitation that could compromise care, require that they make difficult allocation decisions, and contribute to moral distress. Furthermore, unprecedented challenges to caring for patients during the pandemic, including the need to limit in-person interactions, the rapid pace of change, and the dearth of scientific evidence, added to the challenges of caring for patients and communicating with families. <h3>Conclusions and Relevance</h3> The findings of this qualitative study highlighted the complexity of providing high-quality care for patients during the COVID-19 pandemic. Expanding the scope of institutional planning to address resource limitation challenges that can arise long before declarations of crisis capacity may help to support frontline clinicians, promote equity, and optimize care as the pandemic evolves.
Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals
Authors: Mina Gaga, Joanna Chorostowska-Wynimko, Ildikó Horváth, Martin C. Tammemagi, David Shitrit, Vered H. Eisenberg, Hao Liang, David Stav, Dan Levy Faber, Maarten Jansen, Yael Raviv, Vasileios Panagoulias, Piotr Rudzinski, Gabriel Izbicki, Ohad Ronen, Adiv Goldhaber, Rawia Moalem, Nadir Arber, Ilana Haas, Qinghua Zhou
Journal: European Respiratory Journal (2020)

Aim Lung cancer screening reduces mortality. We aim to validate the performance of Lung EpiCheck, a six-marker panel methylation-based plasma test, in the detection of lung cancer in European and Chinese samples. Methods A case–control European training set (n=102 lung cancer cases, n=265 controls) was used to define the panel and algorithm. Two cut-offs were selected, low cut-off (LCO) for high sensitivity and high cut-off (HCO) for high specificity. The performance was validated in case–control European and Chinese validation sets (cases/controls 179/137 and 30/15, respectively). Results The European and Chinese validation sets achieved AUCs of 0.882 and 0.899, respectively. The sensitivities/specificities with LCO were 87.2%/64.2% and 76.7%/93.3%, and with HCO they were 74.3%/90.5% and 56.7%/100.0%, respectively. Stage I nonsmall cell lung cancer (NSCLC) sensitivity in European and Chinese samples with LCO was 78.4% and 70.0% and with HCO was 62.2% and 30.0%, respectively. Small cell lung cancer (SCLC) was represented only in the European set and sensitivities with LCO and HCO were 100.0% and 93.3%, respectively. In multivariable analyses of the European validation set, the assay's ability to predict lung cancer was independent of established risk factors (age, smoking, COPD), and overall AUC was 0.942. Conclusions Lung EpiCheck demonstrated strong performance in lung cancer prediction in case–control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations.
Serum Soluble Syndecan-1 (ssCD138) Can Contribute to the Discrimination of Lenalidomide Resistant Multiple Myeloma (MM) Patients
Authors: Annita Ioanna Gkioka, Aspasia Koudouna, Vasiliki Bartzi, Maria Dimou, Theodoros Iliakis, Aikaterini Bitsani, Vasileios Pardalis, Panayiotis Panayiotidis, Marie-Christine Kyrtsonis
Journal: Blood (2020)
Abstract 426: Effects of Non-syndromic Mitral Valve Prolapse on Valvular Interstitial Cell Extracellular Vesicle-associated Non-coding RNA in a Spontaneous Canine Disease Model
Authors: Dawn Meola, Sally Robinson, Vicky Yang
Journal: Circulation Research (2020)

Non-syndromic mitral valve prolapse (MVP), or Barlow’s Disease, is a valvular heart disease with a prevalence of 2-3% in the human adult population. Consequences of MVP include mitral regurgitation that without surgical treatment can progress to congestive heart failure, arrhythmias and sudden death. Since MVP is a degenerative disease that worsens with age, surgical risk is of concern with an older population, necessitating the development of alternative strategies for early detection and effective medical intervention. Similar to humans, canine MVP is age-related with a lifetime prevalence close to 90%, providing a large population for study. Canine MVP represents a relevant spontaneous large animal model to dissect the mechanistic underpinnings of disease pathogenesis and evaluate novel treatment. We hypothesize that extracellular vesicles (EVs) and their associated non-coding RNA (ncRNA) may play a role in this disease by enabling propagation of the fibroblast-to-myofibroblast phenotypic switch in mitral valvular interstitial cells (VICs). VICs were isolated from 12 normal and 14 diseased canine mitral valves and cultured in defined chemical media for 48 hours. EVs were isolated from conditioned media using size exclusion chromatography. Total RNA was isolated from EVs with the Qiagen miReasy Plasma/Serum kit, and from VIC cells with the mirVana miRNA Isolation Kit. Sequencing libraries were created using QIAseq miRNA Library Kit, and RNAseq was performed with Illumina HiSeq 2500 sequencer with single read 100 base format. Reads were mapped to canine ncRNA databases (miRbase, RFam). VICs from diseased valves had higher expression of αSMA than cells from normal valves (p = 0.002) based on RT-qPCR. Sequence analysis showed decreased content of tRNA (p = 0.023) and miRNA precursor (p = 0.036) in EVs from diseased VICs, in addition to decreased expression of let-7f. Cells from diseased valves had lower Y-RNA content (p = 0.007). miR-8859a and miR-451 were preferentially packaged into EVs from both normal and diseased VICs. Preferential packaging of miR-155 was seen in normal VIC EVs and miR-191 in diseased VIC EVs. Functional roles of these miRs will need to be confirmed to determine their therapeutic potential for treatment of MVP.
Inhibition of Critical DNA Dioxygenase Activity in IDH1/2 Mutant Myeloid Neoplasms
Authors: Simona Pagliuca, Yihong Guan, Anand D. Tiwari, Dale Grabowski, Carmelo Gurnari, Cassandra M Kerr, Sunisa Kongkiatkamon, Metis Hasipek, Laila Terkawi, Misam Zawit, Hassan Awada, Valeria Visconte, Yogenthiran Saunthararajah, James G Phillips, Jaroslaw P. Maciejewski, Babal K. Jha
Journal: Blood (2020)
Over-the-counter analgesics during pregnancy: a comprehensive review of global prevalence and offspring safety
Authors: Aikaterini Zafeiri, Rod T Mitchell, David C Hay, Paul A Fowler
Journal: Human Reproduction Update (2020)

Abstract BACKGROUND Analgesia during pregnancy is often necessary. Due to their widespread availability, many mothers opt to use over-the-counter (OTC) analgesics. Those analgesic compounds and their metabolites can readily cross the placenta and reach the developing foetus. Evidence for safety or associations with adverse health outcomes is conflicting, limiting definitive decision-making for healthcare professionals. OBJECTIVE AND RATIONALE This review provides a detailed and objective overview of research in this field. We consider the global prevalence of OTC analgesia during pregnancy, explain the current mechanistic understanding of how analgesic compounds cross the placenta and reach the foetus, and review current research on exposure associations with offspring health outcomes. SEARCH METHODS A comprehensive English language literature search was conducted using PubMed and Scopus databases. Different combinations of key search terms were used including ‘over-the-counter/non-prescription analgesics’, ‘pregnancy’, ‘self-medication’, ‘paracetamol’, ‘acetaminophen’, ‘diclofenac’, ‘aspirin’, ‘ibuprofen’, ‘in utero exposure’, ‘placenta drug transport’, ‘placental transporters’, ‘placenta drug metabolism’ and ‘offspring outcomes’. OUTCOMES This article examines the evidence of foetal exposure to OTC analgesia, starting from different routes of exposure to evidence, or the lack thereof, linking maternal consumption to offspring ill health. There is a very high prevalence of maternal consumption of OTC analgesics globally, which is increasing sharply. The choice of analgesia selected by pregnant women differs across populations. Location was also observed to have an effect on prevalence of use, with more developed countries reporting the highest consumption rates. Some of the literature focuses on the association of in utero exposure at different pregnancy trimesters and the development of neurodevelopmental, cardiovascular, respiratory and reproductive defects. This is in contrast to other studies which report no associations. WIDER IMPLICATIONS The high prevalence and the challenges of reporting exact consumption rates make OTC analgesia during pregnancy a pressing reproductive health issue globally. Even though some healthcare policy-making authorities have declared the consumption of some OTC analgesics for most stages of pregnancy to be safe, such decisions are often based on partial review of literature. Our comprehensive review of current evidence highlights that important knowledge gaps still exist. Those areas require further research in order to provide pregnant mothers with clear guidance with regard to OTC analgesic use during pregnancy.
A New Generation of “Magic Bullets” for Molecular Targeting of Cancer
Authors: Jacek Capala, Charles A. Kunos
Journal: Clinical Cancer Research (2020)

A two-step molecular targeting approach involving a self-assembling and disassembling (SADA) bispecific antibody platform and DOTA-radioconjugates allows tumor-specific delivery of diagnostic and therapeutic payloads. Low immunogenicity and the modular nature of SADA allow its optimization to safely and repeatedly deliver a variety of payloads to tumors expressing diverse tumor-specific antigens.See related article by Santich et al., p. 532.
Offline: COVID-19—a crisis of power
Authors: Richard Horton
Journal: The Lancet (2020)

COVID-19 is about the politics of the body. In a series of lectures and essays in the 1970s and early 1980s, Michel Foucault (who died in 1984) argued that the discipline of public health emerged with the birth of capitalism in the 18th century. The body came to be understood as an instrument of economic production, of labour power, and so became a subject of significant political interest. Medicine and public health were endorsed as tools to enhance these productive forces, to ensure that people were fit for work.
The Prognostic Impact of Dynamic Changes of Genetic Risk Stratification in Multiple Myeloma
Authors: Huishou Fan, Jiahui Liu, Chenglu Yuan, Xue-Han Mao, Xiaoqing LI, Xin Du, Zengjun Li, Mu Hao, Yuting Yan, Shuhui Deng, Chenxing Du, Chengwen Li, Jiawei Zhao, Shuhua Yi, Dehui Zou, Yaozhong Zhao, Fenghuang Zhan, Yu-Tzu Tai, Jianxiang Wang, Kenneth Anderson, Lugui Qiu, Gang An
Journal: Blood (2020)
Trends in Allogeneic Stem Cell Transplantation for Myelofibrosis in Europe between 1995-2018: An EBMT Retrospective Analysis
Authors: Donal P. McLornan, Dirk-Jan Eikema, Nicolaus Kröger, Linda Koster, Tomasz Czerw, Dietrich W. Beelen, Emanuele Angelucci, Marie Robin, Martin Bornhaeuser, Jakob Passweg, Grant McQuaker, Antonin Vitek, Jürgen Finke, Igor W Blau, Riitta Niittyvuopio, Uwe Platzbecker, Jan J. Cornelissen, Patrice Chevallier, Micha Srour, Dragana Stamatovic, Joaquín Martínez-Lopez, Liesbeth C. de Wreede, Patrick J Hayden, Juan Carlos Hernandez Boluda, Ibrahim Yakoub-Agha
Journal: Blood (2020)
Five thousand years of minimal access surgery: 1850 to 1990: Technological developments
Authors: Rachel Hargest
Journal: Journal of the Royal Society of Medicine (2020)

Summary This is the second of a three-part series that charts the history of minimal access surgery from antiquity to current times. Although rapid developments in laparoscopic and robotic surgery have transformed surgical care over the last 30 years, our predecessors made significant advances in their time which set the principles for modern practice. Part I of this series described how ancient medical practitioners developed simple instruments, from metal or wood, for viewing body cavities. Improvements in the use of metal, glass and lighting allowed for inspection of deeper parts of the body. This second part of the series will show how advances in electrical technology allowed the development of improved lighting for endoscopy and laparoscopy along with the use of electrocautery for a wide range of therapeutic procedures.
The role of CD36 in cardiovascular disease
Authors: Hongyang Shu, Yizhong Peng, Weijian Hang, Jiali Nie, Ning Zhou, Dao Wen Wang
Journal: Cardiovascular Research (2020)

Abstract CD36, also known as the scavenger receptor B2, is a multifunctional receptor widely expressed in various organs. CD36 plays a crucial role in the uptake of long-chain fatty acids, the main metabolic substrate in myocardial tissue. The maturation and transportation of CD36 is regulated by post-translational modifications, including phosphorylation, ubiquitination, glycosylation, and palmitoylation. CD36 is decreased in pathological cardiac hypertrophy caused by ischaemia–reperfusion and pressure overload, and increased in diabetic cardiomyopathy and atherosclerosis. Deficiency of CD36 alleviates diabetic cardiomyopathy and atherosclerosis, while overexpression of CD36 eliminates ischaemia–reperfusion damage, together suggesting that CD36 is closely associated with the progression of cardiovascular diseases and may be a new therapeutic target. This review summarizes the regulation and post-translational modifications of CD36 and evaluates its role in cardiovascular diseases and its potential as a therapeutic target.
Treating MRD Positivity in Multiple Myeloma: An Allogeneic GM-CSF-Based Vaccine in Combination with Lenalidomide Induces Long-Term Remissions in Patients with Low Disease Burden
Authors: Luca Biavati, Carol Ann Huff, Anna Ferguson, Lakshmi Rudraraju, Cristina Zucchinetti, Rachel Gittelman, Sarah Johnson, Catherine Sanders, Abbas Abbas Ali, Kimberly Noonan, Ivan M. Borrello
Journal: Blood (2020)
THU0438 INADEQUATE CARE FOR PATIENTS HOSPITALISED WITH GOUT: EVIDENCE THAT EULAR GUIDANCE IS NOT UTILISED
Authors: M. Russell, B. Clarke, S. Rampes, K. Dokal, A. Mahto, A. Rutherford, J. Galloway
Journal: Annals of the Rheumatic Diseases (2020)

Background: Hospitalisations due to gout have increased over the last decade, in direct contrast to declining admissions for other inflammatory arthritides including RA [1]. Gout is a treatable condition with recently published EULAR guidelines [2, 3]. Admissions could be avoided with effective use of urate-lowering therapies (ULT). Objectives: We hypothesised that the majority of patients attending hospital with acute gout attacks would not be on ULT. Furthermore, we hypothesised that the majority of patients would not be provided with a plan for ULT commencement and/or uptitration on discharge, leaving them at risk of further hospitalisations. Methods: We retrospectively analysed electronic health records for all patients presenting acutely with a primary admission diagnosis of gout (ICD-10 code: M10) at two hospitals in London, UK, from January – December 2017. Analyses of in-hospital gout management were performed for these patients, including to ascertain the number and proportion of patients who: i) had a known history of gout; ii) were receiving ULT at time of attendance; iii) were provided with a discharge plan for ULT commencement and/or uptitration. Results: Over a 12-month period, there were 234 emergency attendances for gout in 225 individuals. 80% were male, with a mean age of 58 years. 70/234 (30%) attendances resulted in admission to hospital (mean length of stay: 2 days; range: 0-31 days). 211 patients had routinely captured clinical data available for further analysis. 90/211 (43%) patients had prior diagnoses of gout, of whom 38% were on ULT at presentation (32 allopurinol, 2 febuxostat). 38% of patients were discharged with a plan for ULT commencement and/or uptitration. 20 patients re-presented to hospital with acute gout within 12 months (17/20 were not receiving ULT). Conclusion: Most patients hospitalised with gout were not receiving ULT, even those with a prior history of gout attacks. Few were provided with a ULT plan, leaving them at risk of re-admission to hospital. Hospital admissions are unpleasant for patients and incur a high economic burden for health services; if they are to be prevented, there must be a concerted effort to implement and follow gout management guidelines to ensure patients receive ULT at appropriate doses. References: [1]Russell M, et al . Return of the King: Rising Incidence of Acute Hospital Admissions due to Gout. J Rheum 2019 Sep 15. [2]Richette P, et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis 2017;76:29-42. [3]Richette P, et al. 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout. Ann Rheum Dis 2020;79:31-38. Disclosure of Interests: : None declared