tbuckley/cabot-search huggingface dataset:
P04.03 Different role of integrin a6 in glioblastoma proneural and mesenchymal stem-like cells
Authors: E Stanzani, L Pedrosa, G Bourmeau, O Anezo, A Noguera-Castells, L Passoni, N Núria, G Seano, A Tortosa, F Martinez-Soler
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The plasticity of tumoral cells and the presence of cells displaying stem-like features are two interrelated traits of Glioblastoma (GBM) lesions and both concur in defining its heterogeneity. Particularly, GBM stem-like cells (GSC) can be classified according to trascriptional data in different subgroups, being the Proneural (PN-GSC) and the Mesenchymal (MES-GSC) the most consolidated clusters. GSC are responsible of most of the malignant characteristics of GBM, including therapeutic resistance and tumor recurrence. Therefore, a better understanding of the mechanisms regulating GSC responsiveness to therapy taking into account GSC molecular heterogeneity may help to improve patient’s outcome. Integrin a6 is a commonly used marker for GSC capable to enrich for GSC population and sustain stemness. We investigate the role of integrin a6 in both PN and MES GSC on stemness and radioresistance. MATERIAL AND METHODS The expression of integrin a6 was analyzed in GSC cultures obtained from post-surgical specimens either displaying PN or MES trascriptional traits. Using cell sorting to enrich for integrin a6 expression (integrin a6-high and a6-low) and gene silencing with lentiviral-based shRNA, integrin a6 impact on both GSC cultures was tested. Also, silenced MES-GSC were analysed by means of RNA-seq. The major pathways found altered by integrin a6 silencing were validated at functional level using gliomasphere-based clonogenic assay, extreme limiting dilution assay and gamma-H2AX to monitor DNA damage repair kinetics. RESULTS After sorting GSC cultures by integrin a6 expression, PN-GSC a6-low showed a significant reduction in clonogenic capability and gliomasphere size when compared to a6-high (p&amp;lt;0.0001). On the contrary, sorted MES-GSC did not display any differences. Similar results were obtained following integrin a6 lentiviral silencing. However, RNAseq on silenced MES-GSC revealed a significant impact on cell cycle regulation and DNA damage repair pathways. Indeed, Integrin a6 trascriptional inhibition in MES-GSCs impaired the capacity to clear gamma-H2AX foci after ionizing radiation (p&amp;lt;0.001) and significantly alters MES-GSC capacity to recover from radiation treatment in gliomasphere formation assay (p&amp;lt;0.01). According to the interpretation of the curves with the linear quadratic model, integrin a6 silenced cells displayed higher alpha- and beta- values and lower alpha/beta ratio. The obtained values demonstrate increased radiosensitivity and impaired capacity to repair sublethal DNA damage, in addition to an enhanced sensitivity to fractionated doses. CONCLUSION The data obtained showed that Integrin a6 regulates proliferation and stemness-related features in PN-GSC while supports radioresistance of MES-GSCs. Altogether, we reveal that integrin a6 controls different stem-associated features in GSCs depending on the molecular subtype.
Overprescribing: 10% of items dispensed in primary care are inappropriate, review finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

An estimated 10% of items dispensed in primary care in England are inappropriate, a government review into overprescribing has said.

The review, commissioned in 2018, also found that 15% of people took five or more medicines a day, while around one in five hospital admissions in over 65s was caused by adverse effects of medicines.

The report said that the key to stopping overprescribing was “medicines optimisation”—which would mean ensuring that patients had the right medicines prescribed, at the right time, in the right doses. It …
Can high-dose methotrexate be safely administered to outpatients?
Authors: Briana Genge, Tricia Carasco, Leslie Young, Leigha Laporte, Tara D. Baetz
Journal: Journal of Clinical Oncology (2021)

34 Background: High-dose methotrexate (HD-MTX) is administered as prophylaxis for central nervous system (CNS) relapse in Diffuse Large B Cell Lymphoma (DLBCL). It is traditionally administered in an inpatient setting due to its complex supportive care regimen. We developed an outpatient protocol and evaluated the safety of this approach. Methods: In 2019 a multidisciplinary team at Kingston Health Sciences Centre developed an outpatient HD-MTX protocol for CNS prophylaxis in DLBCL. Select eligible patients received their HD-MTX infusion in the day unit and returned daily for bloodwork and monitoring. Leucovorin and continuous intravenous hydration were administered via ambulatory infusion pumps. A single centre retrospective cohort analysis was conducted on all patients who received outpatient HD-MTX. These patients were compared to a historical control group who underwent inpatient HD-MTX and who would have met outpatient eligibility criteria. To evaluate the safety of the outpatient protocol we compared the risk of significant toxicity, defined as an elevation in serum creatinine or oral mucositis of grade III or higher, or development of febrile neutropenia. We also evaluated the time to MTX serum clearance, patient admissions and delays of subsequent chemotherapy cycles. Results: From June 2017 to March 2021, 6 outpatients undergoing 14 HD-MTX cycles and 13 inpatients undergoing 28 cycles were evaluated. Significant toxicity occurred in one outpatient cycle compared to five inpatient cycles (7.1% vs 17.9%, p = 0.79). Average time to MTX clearance was 4.1 days for outpatients and 3.5 days for inpatients (p = 0.013). Only one outpatient was admitted to hospital, resulting in an average length of hospital stay of 0.5 days for outpatients compared to 4.96 days for inpatients. There was no significant difference in the need to delay a subsequent cycle of chemotherapy. Conclusions: Outpatient administration of HD-MTX can be administered safely and effectively as CNS prophylaxis in select patients with DLBCL.[Table: see text]
Abstract 17147: No Changes in Average Lipid Profiles in the United States From 2003 to 2012: The National Health and Nutrition Examination Survey 2003-2012
Authors: Peter P Toth, Michael K Palmer, Karin M Henriksson
Journal: Circulation (2015)

Introduction: Lipid-lowering therapies (LLT) are now regularly used in the management of dyslipidemia, but it is not known how the increased use of LLT has influenced lipid levels of the US population. We determined the average lipid profiles of the US population from 2003-2012 in the National Health and Nutrition Examination Survey (NHANES). Methods: Coronary heart disease risk using NCEP ATP III criteria was assessed in adult participants in 2-yearly NHANES surveys from 2003-2004 to 2011-2012. Fasting serum values were used to determine lipid profiles of men and women in each risk group. The proportion of participants in each risk group receiving LLT was also calculated. Results: Estimates for the US population were based on 11,256 observations in NHANES from 2003-2012. From the 2003-2004 survey to the 2011-2012 survey, a significant increase in the use of LLT was observed in the low- (6% to 11%; p&lt;0.0001) and high-risk (41% to 52%; p=0.008) groups. A possible trend for reduction in median triglyceride (TG) levels was observed in women in the high-risk group only, from 170 mg/dL (2003-2004) to 127 mg/dL (2011-2012). However, sample sizes are small (165-248 participants), and variability is high; therefore, this may impact on the applicability of the TG results. For both men and women and in all risk categories, no obvious trend for change in mean levels of non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), and HDL-C was observed (Figure). Mean HDL-C levels were higher in women than in men in all risk groups, consistently over the time period (Figure). Conclusion: Despite an increase in the use of LLT, we observed no trend for change in lipid profiles in low-, intermediate- or high-risk men and women in the US population. This may be due to the variability in response to LLT, and highlights the need for more aggressive identification and treatment of high-risk individuals, as recommended in the ACC/AHA guideline.
An Introduction to the Bacteriological Examination of Water.
Journal: JAMA (1902)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Outcome of NPM1 Mutated Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMAs): A Report on 71 Cases
Authors: Pedro H Prata, Cecile Bally, Thomas Prebet, Christian Recher, Geoffroy Venton, Xavier Thomas, Emmanuel Raffoux, Arnaud Pigneux, Thomas Cluzeau, Judith Desoutter, Claude Preudhomme, Pierre Fenaux, Lionel Ades
Journal: Blood (2017)
Implementation and impact of Choosing Wisely recommendations in oncology: A scoping review.
Authors: Sonieya Nagarajah, Melanie Lynn Powis, Rouhi Fazelzad, Monika K. Krzyzanowska, Vishal Kukreti
Journal: Journal of Clinical Oncology (2021)

21 Background: The Choosing Wisely (CW) campaign launched in 2012 includes oncology-related recommendations (CWR) aimed at promoting evidence-based care and de-implementing low value practices; however, it remains unclear to what extent practice has changed as a result of the campaign. We undertook a scoping review to evaluate the extent of CWR uptake in oncology, and barriers and facilitators to implementation. Methods: A systematic search of MEDLINE, EMBASE, Cochrane, Emcare Nursing and Scopus was conducted for articles published between 2012 and March 6, 2020 pertaining to cancer-specific CWR. Articles were excluded if they did not report on cancer-specific recommendations, were commentaries/opinions, reported on screening or prevention, focused on pediatric populations, or were not in English. Retained articles were thematically grouped based on study objective. Implementation strategies, barriers and facilitators were summarized for articles implementing a recommendation into practice. Results: The search yielded 8565 articles; 98 articles were retained, addressing 32 unique recommendations. Use of active surveillance for low-risk prostate cancer (14/98) and reduction of imaging in early breast cancer (13/98) were the most commonly evaluated CWR. Of the 29 articles reporting on pre-post CW campaign adherence, 20 reported improved compliance without further intervention. In articles evaluating factors associated with CWR-concordance (62/98), age (23/62), stage or risk (22/62), and geographic location (21/62) most commonly influenced care decisions. Few articles described the development of interventions to improve concordance (1/98) or a protocol to evaluate implementation (2/98) with no further testing of their design. Of the 10/98 articles that evaluated implementation of a CWR, all reported improved compliance (range: 3-73% improvement). Implementation strategies were used in combination and most often included provider education (8/10), stakeholder engagement (6/10), and forced function (4/10). Preconceived views and reluctance to adopt new practices were the most commonly reported barriers to implementation; the use of technology to update practice and the use of education and evidence to build provider buy-in were the most common facilitators. Conclusions: In the eight years since the initial publication of oncology-specific CW recommendations, uptake has been limited. Publication of the recommendations has resulted in some passive improvements in care. Further adoption of CWR likely requires an implementation strategy that includes building stakeholder buy-in, and utilization of updated order sets and forced functions in technology to facilitate change. Future studies should assess the impact of the COVID-19 pandemic on the adoption of CWR and the de-implementation of low-value care.
Myocardial Dysfunction and Heart Failure in Rheumatoid Arthritis
Authors: Elizabeth Park, Jan Griffin, Joan M. Bathon
Journal: Arthritis & Rheumatology (2021)

Rheumatoid arthritis (RA) patients have almost twice the risk of heart failure (HF) as individuals without RA, even with adjustment for the presence of ischemic heart disease. Moreover, RA patients remain at a 2‐fold higher risk of mortality from HF compared to non–RA patients. These observations suggest that RA‐specific inflammatory pathways are significant contributors to this increased risk of HF. Herein we summarize the epidemiology of HF in RA patients, the differences in myocardial structure or function between RA patients and non–RA patients without clinical signs of HF, and data on the role of systemic and local inflammation in RA HF pathophysiology. We also discuss the impact of subduing inflammation through the use of RA disease‐modifying therapies on HF and myocardial structure and function, emphasizing gaps in the literature and areas needing further research.
Hematology/oncology utilization of advance care planning services.
Authors: Natalie R. Dickson, Allison Hirschorn, Brian Bourbeau, Christian A. Thomas, Stephanie Thebarge, Piyush Srivastava, Pamela T. Soliman, Heather Levanduski
Journal: Journal of Clinical Oncology (2021)

25 Background: In 2016, Medicare added coverage for advance care planning (ACP) services (CPT codes 99497 and 99498). ASCO’s Coverage and Reimbursement Steering Group sought to explore and quantify whether these codes are regularly utilized by hematology and oncology physicians, and to provide guidance on administrative best practices for successful reimbursement. Methods: We analyzed utilization of care management services using Physician/Supplier Procedure Summary (2016-2019) and Medicare Provider Utilization and Payment Data: Physician and other Supplier PUF CY2018 (PUF) files, available on data.cms.gov. Data files are limited to lines representing services to at least 11 unique Medicare beneficiaries; otherwise, Medicare imputes a blank value. Total ACP services submitted to Medicare and the total services denied were calculated for each year using the combination of Hematology, Hematology/Oncology, and Medical Oncology (collectively Hematology/Oncology) specialties, as well as for all specialties. Within Hematology/Oncology, we also pulled physician-level data for 6,335 physicians who had billed Medicare for at least 500 office or hospital outpatient evaluation and management services in 2018. Totals for codes 99497 and 99498 were calculated per physician, providing a distribution of volume. Results: Specialty utilization of ACP services has increased each year, from 708,183 submitted services in 2016 to 2,043,767 in 2019. Hematology/Oncology utilization increased from 2016 to 2017, followed by declines in volume for 2018 and 2019. Among 6,355 hematology/oncology physicians submitting at least 500 office or hospital outpatient evaluation and management visits, 145 billed Medicare at least 11 ACP services in either a facility or non-facility setting. Advance Care Planning Services (99497 and 99498) billed to Medicare in 2016-2019. Conclusions: Though Advance Care Planning is an integral part of cancer care, the codes are not frequently reported to Medicare as a separate service. This may be due to lack of awareness or understanding of the codes, and uncertainty as to how to implement the services into the workflow of the practice. To increase utilization and ensure appropriate reporting of ACP, Oncologists and Oncology practices would benefit from coding and reporting education, and well as guidance on administrative processes to successfully manage ACP services. ASCO's Coverage and Reimbursement Steering Group has developed a practice administration and reimbursement guide for publication on asco.org.[Table: see text]
Associations With Definitive Outcomes and Clinical Benefit of Cancer Drugs at the Time of Marketing Approval and in the Postmarketing Period
Authors: Aida Bujosa, Consolación Moltó, Thomas J. Hwang, José Carlos Tapia, Kerstin N. Vokinger, Arnoud J. Templeton, Ignasi Gich, Agustí Barnadas, Eitan Amir, Ariadna Tibau
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Most anticancer drugs are approved by regulatory agencies based on surrogate measures. This article explores the variables associated with overall survival (OS), quality of life (QoL), and substantial clinical benefit among anticancer drugs at the time of approval and in the postmarketing period. Methods: Anticancer drugs approved by the FDA between January 2006 and December 2015 and with postmarketing follow-up until April 2019 were identified. We evaluated trial-level data supporting approval and any updated OS and/or QoL data. We applied the ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) and the ASCO Value Framework (ASCO-VF) to initial and follow-up studies. Results: We found that 58 drugs were approved for 96 indications based on 96 trials. At registration, approval was based on improved OS in 39 trials (41%) and improved QoL in 16 of 45 indications (36%). Postmarketing data showed an improvement in OS for 28 of 59 trials (47%) and in QoL for 22 of 48 indications (46%). At the time of approval, 25 of 94 (27%) and 26 of 80 scorable trials (33%) met substantial benefit thresholds using the ESMO-MCBS and ASCO-VF, respectively. In the postmarketing period, 37 of 69 (54%) and 35 of 65 (54%) trials met the substantial benefit thresholds. Drugs with companion diagnostics and immune checkpoint inhibitors were associated significantly with substantial clinical benefit. Conclusions: Compared with the time of approval, more anticancer drugs showed improved OS and QoL and met the ESMO-MCBS or ASCO-VF thresholds for substantial benefit over the course of postmarketing time. However, only approximately half of the trials met the threshold for substantial benefit. Companion diagnostic drugs and immunotherapy seemed to be associated with greater clinical benefit.
Recurrent inference machines as inverse problem solvers for MR relaxometry
Authors: E.R. Sabidussi, S. Klein, M.W.A. Caan, S. Bazrafkan, A.J. den Dekker, J. Sijbers, W.J. Niessen, D.H.J. Poot
Journal: Medical Image Analysis (2021)

In this paper, we propose the use of Recurrent Inference Machines (RIMs) to perform T 1 and T 2 mapping.The RIM is a neural network framework that learns an iterative inference process based on the signal model, similar to conventional statistical methods for quantitative MRI (QMRI), such as the Maximum Likelihood Estimator (MLE).This framework combines the advantages of both data-driven and modelbased methods, and, we hypothesize, is a promising tool for QMRI.Previously, RIMs were used to solve linear inverse reconstruction problems.Here, we show that they can also be used to optimize non-linear problems and estimate relaxometry maps with high precision and accuracy.The developed RIM framework is evaluated in terms of accuracy and precision and compared to an MLE method and an implementation of the Residual Neural Network (ResNet).The results show that the RIM improves the quality of estimates compared to the other techniques in Monte Carlo experiments with simulated data, test-retest analysis of a system phantom, and in-vivo scans.Additionally, inference with the RIM is 150 times faster than the MLE, and robustness to (slight) variations of scanning parameters is demonstrated.Hence, the RIM is a promising and flexible method for QMRI.Coupled with an open-source training data generation tool, it presents a compelling alternative to previous methods.
OS10.8.A The effectiveness of antiepileptic drug duotherapies in glioma patients: a multicenter observational cohort study
Authors: P B van der Meer, L Dirven, M Fiocco, M Vos, M C M Kouwenhoven, M J van den Bent, M J B Taphoorn, J A F Koekkoek
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND About 30% of glioma patients need an add-on antiepileptic drug (AED) due to uncontrolled seizures on AED monotherapy. This study aimed to determine whether levetiracetam combined with valproic acid (LEV+VPA), a commonly prescribed duotherapy, is more effective than other duotherapy combinations including either LEV or VPA in glioma patients. MATERIAL AND METHODS In this multicenter retrospective observational cohort study, treatment failure (i.e. replacement by or addition of a new AED, or withdrawal of an AED) for any reason was the primary outcome. Secondary outcomes included: 1) treatment failure due to uncontrolled seizures; and 2) treatment failure due to adverse effects. Time to treatment failure was defined as the time from the start of AED duotherapy until the time of treatment failure. Multivariable Cox proportional hazard models were estimated to study the association between risk factors and treatment failure. The maximum duration of follow-up was 36 months. RESULTS A total of 1435 patients were treated with first-line monotherapy LEV or VPA, of which 355 patients received AED duotherapy after they had treatment failure due to uncontrolled seizures on monotherapy. LEV+VPA was prescribed in 66% (236/355) and other AED duotherapy combinations including LEV or VPA in 34% (119/355) of patients. Patients using other duotherapy versus LEV+VPA had higher risk of treatment failure for any reason (cause-specific hazard ratio [csHR]=1.50 [95%CI=1.07–2.12], p=0.020), treatment failure due to uncontrolled seizures (csHR=1.73 [95%CI=1.10–2.73], p=0.018). There were no differences in failure due to adverse effects (csHR=0.88 [95%CI=0.47–1.67]), p=0.703) between the two groups. CONCLUSION This observational cohort study suggests that LEV+VPA has better efficacy than other AED combinations. Similar toxicities were experienced in the two groups.