tbuckley/cabot-search huggingface dataset:
5-ALA fluorescence based isolation of minority population GBM cells identifies putative invasion associated molecular changes
Authors: Maria de los Angeles Estevez-Cebrero, Anbarasu Lourdusamy, Ruman Rahman, Stuart Smith
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is a highly pleomorphic polyclonal tumour with molecular abnormalities varying temporo-spatially (intra-tumour heterogeneity), one mechanism of therapy resistance. Fluorescence guided resection (FGR) is performed with prior administration of 5-aminolevulinic acid (5-ALA) leading to individually fluorescent tumour cells mixed within a background population of non-neoplastic neural cells in the invasive region beyond the “pure” tumour. We have isolated this invasive tumour population by fluorescence activated cell sorting (FACS) to allow the study of invasive tumour cells without an overwhelming background “normal” signal. We conducted genome wide gene expression of phenotypically distinct areas of the tumour and from fluorescent/non-fluorescent cancer/non-cancer cells purified from the invasive zone respectively. We performed genome-wide gene expression analysis on 14 glioma samples from three different GBM patients including samples from tumour core, rim, invasive margin and GBM cells from the invasive margin that were isolated by 5-ALA assisted FACS. Statistical analysis by linear models for microarray data identified 325 differentially expressed genes between FACS positive cells and other tumour regions (adjusted P-value < 0.05), of these, 50 genes were upregulated in all comparisons. These transcriptomic changes orchestrate MAPK (DUSP1, DUSP2, DUSP10 and FOSB), chemokine signalling pathways (CXCL2, CXCL3, CCL20 and NFKB1) and negative regulation of cell proliferation (EREG and KLF6). In contrast, 29 downregulated genes in FACS positive cells were enriched with signal transduction (DDR2 and MTSS1L) and ECM-receptor interaction (COL4A1, COL4A2, and HSPG2). Residual cells responsible for GBM recurrence in the invasive zone are shown to be not only phenotypically different but also exhibiting activation of distinct molecular pathways and biological processes. These unique molecular features offer hope for developing more efficacious targeted therapies focusing on this population rather than the bulk tumour that has been the subject of most historical analyses.
PBI-4050, A NOVEL FIRST-IN-CLASS AGENT, REDUCES PULMONARY HYPERTENSION, LUNG REMODELING AND RIGHT VENTRICULAR DYSFUNCTION IN HEART FAILURE
Authors: Jocelyn Dupuis, Quang T. Nguyen, Martin G. Sirois, Angelino Calderone, Jean-Claude Tardif, YanFen Shi, Alexandre Laverdure, Brigitte Grouix, Lyne Gagnon
Journal: Journal of the American College of Cardiology (2018)
Alan Maynard: the “Voltaire of health economics”
Authors: Maria Goddard
Journal: BMJ (2018)

“I will not have my health policies dictated by some punk professor from York.”

Whether the then health secretary, Ken Clarke, actually used those words, they proved prophetic. Many key NHS polices of the 1990s and 2000s were indeed inspired—if not dictated—by Alan Maynard, through his razor sharp wit and inimitable maverick style of communication.

Appointed as a lecturer to the University of York in 1971, Alan led the way in health economics and health policy for the best part of half a century, creating York’s MSc in health economics, founding the Centre for Health Economics, and launching the journal, Health Economics .

The combination of bold and challenging views, delivered in his trademark acerbic style, made Alan a formidable “intellectual agent provocateur”—an approach that won him both friends and foes in the medical profession. His passion was evidence—its creation and use to inform and evaluate health policy—and he deplored the constant “re-disorganisation” of the NHS based on political whim or the influence of powerful interest groups. As an economist, he also knew that …
Hip and Knee Replacements
Authors: Vanessa Lam, Steven Teutsch, Jonathan Fielding
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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) 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
POPULATION-SPECIFIC GENETIC VARIATIONS INCREASE HAZARD OF MORTALITY OR REHOSPITALIZATION IN HEART FAILURE PATIENTS
Authors: David E. Lanfear, Hongsheng Gui, Jia Li, Thomas Connolly, Naveen Pereira, She Ruicong, Kirkwood Adams, L. Keoki Williams, Adrian Hernandez, Wai Hong Tang, Francke Stephan
Journal: Journal of the American College of Cardiology (2018)
Cytomegalovirus Reactivation Does Not Increase Subsequent Risk for Acute Graft-Versus-Host Disease, Malignant Disease Relapse, or Infection Following Allogeneic Hematopoietic Cell Transplantation
Authors: Jeffery J Auletta, Monica I Ardura, Sumithira Vasu, Ying Huang, Qiuhong Zhao, Amy S. Ruppert, Abigail Shoben, Patrick Elder, Anissa Bingman, Rhonda Kitzler, Gerard Lozanski, Rolla Abu-Arja, Hemalatha G. Rangarajan, Rajinder Bajwa, Edwin M Horwitz, Lynn O'Donnell, Samantha Jaglowski, Rebecca B Klisovic, Sam Penza, Yvonne A Efebera, Craig C Hofmeister, Ashley E Rosko, Don M Benson, Leslie A. Andritsos, William Blum, Steven M Devine
Journal: Blood (2016)
The role of early rehabilitation and symptom management in neuro-oncology
Authors: Rose Marshall, Nicola Peat
Journal: Neuro-Oncology (2018)

Central nervous system (CNS) tumours are associated with debilitating physical and psychological sequlea resulting in reduced functional independence and quality of life (QoL). Nationally access to support and rehabilitation services should be offered to all patients with a CNS tumour throughout their treatment pathway (LCA 2014, NICE 2004). The aim was to develop an integrated rehabilitation model of care that optimises patient care through an active and planned approach; reviewing symptoms, rehabilitation and support needs at all stages of disease. All new neuro-oncology patients attending outpatient consultant clinics at Guy’s Cancer Centre were offered a holistic rehabilitation assessment to identify their individual concerns. The assessments were completed by a specialist Physiotherapist and or Occupational therapist and individual intervention plans were created. Over a 6 month period, July to December 2016, data was collected on patient characteristics, symptom concerns, QoL indicators, onward referrals and patient experience. 64 patients completed the assessments with 92% reporting unmet concerns. Of those reporting concerns the most common symptoms highlighted were; fatigue (83%), emotions/mood (72%), limb weakness (67%) difficulties managing daily activities (65%), mobility and falls (63%), sleep concerns (54%), memory/concentration (52%), appetite/weight (39%) and pain (18%). 59 patients went on to receive rehabilitation interventions. The most common referrals were to specialist cancer rehabilitation services (71%). Other referrals included social services (26%) and rapid response home teams (44%). Case reviews demonstrated; optimisation of mobility and physical function and admission avoidance. Patient outcomes have included improved symptom control, ability to work and satisfaction in managing activities of daily living. Providing neuro-oncology patients with early assessment of their rehabilitation concerns has enabled timely implementation of their rehabilitation care plan. This has been integral in reducing avoidable admissions and improving patient’s level of symptom burden and QoL.
Possible Underestimation of the Provision of Palliative Care
Authors: Hilde M. Buiting, Tjomme de Graas
Journal: JAMA Oncology (2018)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
AXIN deficiency in human and mouse hepatocytes induces hepatocellular carcinoma in the absence of β-catenin activation
Authors: Shirley Abitbol, Rajae Dahmani, Cédric Coulouarn, Bruno Ragazzon, Bernhard Mlecnik, Nadia Senni, Mathilde Savall, Pascale Bossard, Pierre Sohier, Valerie Drouet, Emilie Tournier, Florent Dumont, Romain Sanson, Julien Calderaro, Jessica Zucman-Rossi, Mireille Vasseur-Cognet, Pierre-Alexandre Just, Benoît Terris, Christine Perret, Hélène Gilgenkrantz
Journal: Journal of Hepatology (2018)
Abstract P3-05-09: Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer
Authors: U Toh, S Saku, N Iwakuma, Y Takao, M Okabe, M Akashi, A Yamada, S Shichijo, K Itoh, Y Akagi
Journal: Cancer Research (2018)

Abstract Background: We have previously reported the prognostic role of humoral antigen spreading response against prostate-related antigen (PRA) for metastatic recurrent breast cancer (mrBC) patients who received personalized peptide vaccine (PPV) therapy (Toh U, SABCS 2015). The prognostic effect was additionally evaluated by the clinical relevant factors including intrinsic subtype, the regimens of combined chemo-hormonal therapies in present study. Methods:We analyzed serum IgG responses to all of the peptide candidates included PRAs (PSA, PAP and PMSA) after PPV therapy by the Luminex systemusing peripheral blood samples from 77 vaccinated mrBC patients. The clinical factors and relevant events were statistically evaluated. Results: After 6 and 12cycles of PPV therapy, the serum IgG of anti-PSA, anti-PAP, and/or anti-PMSA increased significantly in 31 patients (PRA response group), and the median progression free survival (PFS) and median overall survival (OS) were 8.1 and 14.3 months, but were 5.1 and 10.8 months, respectively, in the remaining 46 patients with no anti-PRA IgG response (PRA non-response Group). The anti-PRA IgG level was marginally correlated withPFS (p=0.059) and OS (p=0.082) between these two groups, which was a significant prognostic factor for PFS (Log-rank: 0.009) in estrogen-positive cancer patients (ER+). The statistical analyses showed that the clinical outcome was in favor of &amp;gt; 60 year-old patients, those with longer PPV therapies (&amp;gt;3 months), and those who received combined standard hormonal therapies or bisphosphonate/anti-RANKL therapy. Conclusions: This study indicated a clinical significance between the pre-and post- PPV therapy measurement of serum anti-PRA IgG in patients with mrBC, which may be a useful prognostic marker for monitoring peptide vaccine treatment outcomes, particularly for patients &amp;gt; 60 years with ER+ breast cancer. These results also suggest that the immunotherapeutic peptide vaccine could be efficiently combined with hormonal therapy, anti-HER2 therapy, and bisphosphonate/anti-RANKL therapy in mrBC patients. Citation Format: Toh U, Saku S, Iwakuma N, Takao Y, Okabe M, Akashi M, Yamada A, Shichijo S, Itoh K, Akagi Y. Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-09.
Survival for small, well-differentiated PNETs in relation to treatment.
Authors: bao-Quynh Julian, Philip HG Ituarte, Zeljka Jutric, Gagandeep Singh, Isaac Benjamin Paz, Aaron G Lewis
Journal: Journal of Clinical Oncology (2018)

222 Background: Management of small well-differentiated pancreatic neuroendocrine tumors (PNETs) is controversial, and the malignant potential remains uncertain. Treatment options include observation (OB), enucleation (ENUC), and formal resection (Distal pancreatectomy – DP, Whipple/Total pancreatectomy – PD). Our objective was to analyze the association between treatment types of small PNETs and overall survival (OS). Methods: The California Cancer Registry linked with the Office of Statewide Health Planning and Development inpatient database was queried from 2000-2012 for patients with &lt; 3 cm, nonfunctional, stage I–II PNETs. Exclusion: poorly-differentiated PNETs or metastases within 6 months. Non-parametric statistics (Kruskal-Wallis) or Fisher’s exact test were used to determine if any patient characteristics were associated with type of treatment (surgery or observation). Ten-year OS was estimated by the Kaplan-Meier method. A multivariate model was performed using Cox proportional hazards. Results: Of 1,862 patients with PNETs, 204 were small, well-differentiated. Treatments include: OB n = 41, EN n = 20, DP n = 106, or PD n = 67. Few patients developed distant recurrences past 6 months (OB, n = 0; EN, n = 0; DP, n = 2; PD, n = 1). On bivariate analysis, comorbidities (2 or more, p = 0.024), insurance type (p = 0.018), and mean number of lymph nodes retrieved (EN = 1.8 +/- 4.1; DP = 6.3 +/- 7.63; PD = 11.0 +/-8.5) were associated with treatment. Patient gender, race, socio-economic status, hospital type, tumor size, grade (well vs. moderate), and lymph node status at diagnosis were not associated with treatment type. On multivariate analysis, treatment type was not associated with worse OS (p = 0.098). Ten-year OS was similar between treatment groups (OB = 92%, EN = 100%, DP = 95%, PD = 95%, p= 0.1828). Conclusions: In this unique study accounting for time of metastasis in patients who present with early stage, well-differentiated PNETs, observation, enucleation, and resection are equally associated with long-term survival. In the appropriately selected patient group, enucleation or observation may be alternatives to more aggressive surgery.
Rise in mortality in England and Wales in first seven weeks of 2018
Authors: Lucinda Hiam, Danny Dorling
Journal: BMJ (2018)

Re: Rise in mortality in England and Wales in first seven weeks of 2018 Hiam and Dorlings [1] editorial and analysis is a welcomed contribution and timely prompt to keep the focus on the worsening health outcomes across England and Wales.Whilst evidence suggest life expectancy is likely to reduce for men and women in the United Kingdom (UK) [2], alongside a rise in infant mortality in the poorest families [3], it is critical attention remains focused on a key potential cause, austerity driven policy measures, especially for those in poverty.
NHS trusts face “significant” shortages of trainees and consultants, NHS Improvement warns
Authors: Matthew Limb
Journal: BMJ (2016)

NHS trusts continue to face “significant” shortages of trainees and consultants in some specialties, a report by NHS Improvement has warned.

The report said that there were “significant” shortages in some specialties “despite expansion in the consultant workforce more than keeping pace with activity.”1 It said there were difficulties in recruiting consultants as well as increased spending on temporary locums in emergency medicine, acute general medicine, diagnostic services, and …
Physical activity to improve health: do not forget that the lungs benefit too
Authors: Luis Puente-Maestu, William W. Stringer
Journal: European Respiratory Journal (2018)

In this issue of the European Respiratory Journal , Hancox and Rasmussen [1], present an analysis of data from two cohorts, one from Denmark and the other from New Zealand, demonstrating that, in cross-sectional analyses at all ages in both cohorts, aerobic fitness during the childhood and adolescence period was positively associated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) (figures 1 and 2). This association persisted despite independently adjusting for height, weight, sex, current asthma and current smoking. Each standard deviation difference in fitness was associated with a modestly higher predicted values for FEV1 and FVC (2–3%). Physically active children will enjoy better lung function in adulthood <http://ow.ly/P1Pk30hFIPS>
Disease Control Priorities, 3rd edition: cancer package principles and overview
Authors: Hellen Gelband, Susan Horton, David Watkins, Dean T Jamison, Daphne Wu, Mary Gospodarowicz, Prabhat Jha
Journal: The Lancet Global Health (2018)

Most of the global cancer burden is in low-income and middle-income countries (LMICs), and their share of the burden is increasing. However, the needed investment in cancer control has not kept pace. As part of the third volume, on cancer, of the World Bank's latest edition of Disease Control Priorities,1Gelband H Jha P Sankaranarayanan R Horton S Volume 3: cancer. Disease control priorities. 3rd edn. World Bank, Washington, DC2015Crossref Google Scholar we designed a package of essential cancer control interventions to provide policy makers and funders with an adaptable model package of services for expanding locally appropriate cancer control that can be implemented over time and together with expanding universal health coverage.2Gelband H Sankaranarayanan R Gauvreau CL et al.Costs, affordability, and feasibility of an essential package of cancer control interventions in low-income and middle-income countries: key messages from Disease Control Priorities.Lancet. 2016; 387 (3rd edition): 2133-2144Summary Full Text Full Text PDF PubMed Scopus (99) Google Scholar Included interventions meet effectiveness, cost-effectiveness, feasibility, and affordability criteria using analytical methods that are replicable for customising packages to local needs. We sought cost and cost-effectiveness data for a wide range of effective cancer interventions that address significant cancer burdens, with preference for data from LMICs. We applied standard criteria to these, in combination with epidemiological data, to define a set of interventions that could be considered appropriate in many LMICs. The defined package includes: prevention of tobacco-related cancer and virus-related liver and cervical cancers; diagnosis and treatment of early breast cancer, cervical cancer, and selected childhood cancers; and widespread availability of palliative care, including opioid drugs. Once initial investments were made in infrastructure and personnel, these interventions would cost an additional US$20 billion per year worldwide, or about 3% of current public sector health spending in LMICs. Implementation of a locally appropriate cancer control package would substantially reduce suffering and premature death from cancer before 2030 and result in even greater improvements thereafter. It will take years to decades to build national cancer control systems, particularly in low-income countries, but delaying planning and first steps will only delay the realisation of competent cancer control. We declare no competing interests.
Real-world survival and treatment patterns of patients with locally advanced or metastatic urothelial carcinoma treated with second-line therapy after platinum-based chemotherapy.
Authors: Jason C Simeone, Beth L Nordstrom, Ketan Patel, Alyssa B Klein, Laura Horne
Journal: Journal of Clinical Oncology (2018)

466 Background: Median overall survival for patients with locally advanced/metastatic urothelial carcinoma (UC) who fail standard platinum-containing chemotherapy is 5–7 months, and there is no current standard of care for these patients. As immuno-oncology (IO) therapies are being developed for the treatment of UC, including some recent approvals, a better understanding of the current real-world treatment patterns and effectiveness of treatments is needed. Methods: Patients with locally advanced/metastatic UC receiving second-line therapy after platinum-based chemotherapy were identified from the Flatiron Oncology electronic medical record database from 2011–2016. Treatment patterns, including the most common regimens and total number of systemic therapy treatment lines, were characterized. Median overall survival (OS) and associated 95% confidence intervals (CI) were calculated from the start of second-line therapy using Kaplan-Meier curves. Results: A total of 476 patients met all study criteria; mean age was 70.1 ± 9.2 years and 74.2% were male; &lt;3% were tested for PD-L1 during follow-up. Platinum-based chemotherapies were most commonly prescribed (Table 1), 4.4% received IO during second-line. Median OS from start of second-line therapy was 8.3 months (95% CI: 7.2–8.9). Conclusions: Real-world OS among locally advanced/metastatic UC patients who received second-line therapy after platinum-based chemotherapy was less than one year, similar to prior estimates. It remains to be seen how the introduction and increasing uptake of IO may affect OS. [Table: see text]