tbuckley/cabot-search huggingface dataset:
Safe Handling of Hazardous Drugs: ASCO Standards
Authors: Paul Celano, Christopher A. Fausel, Erin B. Kennedy, Tim M. Miller, Thomas K. Oliver, Ray Page, Jeffery C. Ward, Robin T. Zon
Journal: Journal of Clinical Oncology (2019)

To provide 2019 ASCO standards on the safe handling of hazardous drugs.An Expert Panel was formed, and a systematic review of the literature on closed system transfer devices was performed to May 2017 using PubMed. The Cochrane Database of Systematic Reviews, PubMed, and Google Scholar were used to search for studies of medical surveillance and external ventilation/health effects of exposure to vapors to November 2017. Available standards were considered for endorsement. Public comments were solicited and considered in preparation of the final manuscript.The search for primary research found no studies that addressed health outcomes as they relate to the identified interventions of interest. The ASCO Expert Panel endorses the best practices for safe handling of hazardous drugs as issued by the Occupational Safety and Health Administration, US Pharmacopeia Chapter 800, and Oncology Nursing Society with clarifications in four key areas: medical surveillance, closed system transfer devices, external ventilation of containment secondary engineering controls or containment segregated compounding areas, and alternative duties.The ASCO standards address the need for clear standards concerning safe handling of hazardous oncology drugs. More research is needed in several key areas to quantify the level of risk associated with handling hazardous drugs in current workplace settings where the hierarchy of controls is consistently applied. Additional information is available at www.asco.org/safe-handling-standards .
AB1098 Early prosthesis implantation is possible in patients affected by juvenile idiopathic arthritis, treated with biologics: a monocentric experience of 160 prosthesis from the last twenty years
Authors: I. Pontikaki, M. Truzzi, T. Ubiali, L.M. Argolini, S. De Martinis, F. Campanaro, R. Viganò
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The main reasons for prosthesis implantation in a young patient are post-traumatic osteoarthritis, congenital dysplasia and autoimmune diseases involving joints, like Juvenile Idiopathic Arthritis (JIA). Often, related to particular anatomic conditions and severe grade of deformity, there may be a need for special (custom made or revision) components of prosthesis. Biologic therapy in severe, refractory JIA has permitted to obtain a better control of the disease so as to procede with prosthesis implantations (hip, knee, ankle). <h3>Objectives</h3> The aim of the study was to present a monocentric experience of a transitional care centre for JIA and the outcome of early prosthesis implantation in patients treated with biologics. <h3>Methods</h3> 160 prosthesis implantation (72 Hip arthroprosthesis, 71 Knee arthroprosthesis and 17 Ankle arthroprosthesis) were performed beetween 1999 and 2017. It was defined a wash-out period from the biologic therapy depending on the half-life of the medication. The survival of the implant was evaluated for a period of 10 years. We evaluated the different type of implants and it was proposed a radiographic classification for every type of implant. <h3>Results</h3> All patients included in the study were treated with biologics. A long-term analysis of the following ten years of follow-up proved an average survival of 95.5% of the prosthesis and good results in term of function and comfort for the patients. Complications in 2% (two trochanter detachment, two sepsis and one peri-operative haemorrhage). <h3>Conclusions</h3> Prosthesis implantation for JIA patients is a complicated and difficult procedure in comparison with the traditional approach used in patients affected by osteoarthritis. This is related to the management of the biologic therapy, the low quality of the bone, the remarkable stiffness and deformity of the joints. Long-term results were good, even in patients with severe arthritis. There was a drastic reduction of articular pain and an improvement of functionality. Prosthesis implantation in patients with active disease and mild or bad response to the biologics had a worse outcome. The use of not cement-retained implants doesn't influence the long-term survival at ten years, similar to that of the adult patients affected by osteoarthritis. <h3>Disclosure of Interest</h3> None declared
Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Andrew X Zhu, Yoon-Koo Kang, Chia-Jui Yen, Richard S Finn, Peter R Galle, Josep M Llovet, Eric Assenat, Giovanni Brandi, Marc Pracht, Ho Yeong Lim, Kun-Ming Rau, Kenta Motomura, Izumi Ohno, Philippe Merle, Bruno Daniele, Dong Bok Shin, Guido Gerken, Christophe Borg, Jean-Baptiste Hiriart, Takuji Okusaka, Manabu Morimoto, Yanzhi Hsu, Paolo B Abada, Masatoshi Kudo
Journal: The Lancet Oncology (2019)
Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance
Authors: Daisuke Muraoka, Naohiro Seo, Tae Hayashi, Yoshiro Tahara, Keisuke Fujii, Isao Tawara, Yoshihiro Miyahara, Kana Okamori, Hideo Yagita, Seiya Imoto, Rui Yamaguchi, Mitsuhiro Komura, Satoru Miyano, Masahiro Goto, Shin-ichi Sawada, Akira Asai, Hiroaki Ikeda, Kazunari Akiyoshi, Naozumi Harada, Hiroshi Shiku
Journal: Journal of Clinical Investigation (2019)

Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition–sensitive and –resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+ tumor–associated macrophages (TAMs) as a key factor correlated with immune resistance. In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. Targeted delivery of a long peptide antigen to TAMs by using a nano-sized hydrogel (nanogel) in the presence of a TLR agonist activated TAMs, induced their antigen-presenting activity, and thereby transformed the resistant tumors into tumors sensitive to adaptive immune responses such as adoptive transfer of tumor-specific T cell receptor–engineered T cells. These results indicate that the status and function of TAMs have a significant impact on tumor immune sensitivity and that manipulation of TAM functions would be an effective approach for improving the efficacy of immunotherapies.
Wearable Devices for Cardiac Rhythm Diagnosis and Management
Authors: James E. Ip
Journal: JAMA (2019)

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SAT0558 Pharmacotherapy of obesity in patients with knee osteoarthritis and metabolic syndrome
Authors: E. Strebkova, L. Alekseeva
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarthritis (OA) is one of most common diseases of locomotor system. Different OA phenotypes are currently identified, including metabolic OA associated with meta-inflammation induced by obesity and metabolic syndrome. <h3>Objectives</h3> To assess orlistat pharmacotherapy in patients with knee OA (KOA) and metabolic syndrome. <h3>Methods</h3> 50 female patients with Kellgren-Lawrence stage II-III KOA were randomised into 2 equal groups in a 6 months study. All pts were administered lifestyle changes by increasing physical activity and limiting calories (1200 ckal), and patients from Group 1 were additionally treated with orlistat 120 mg 3 times a day. WOMAC and EQ-5D scores and anthropometric data were regularly obtained during the study; biochemistry panel (lipid profile, glucose, CRP), leptin and interleukin-6 were assessed at baseline and at Mo 6. <h3>Results</h3> Metabolic syndrome (MS) was diagnosed at baseline in 41 patients. Following orlistat therapy pts from Group 1 managed to reduce their body weight by 10,07% (<i>p</i>&lt;0,05; Fig 1), and waist circumference (WC) by 7,5% (<i>p</i>&lt;0,05), improving the clinical course of OA: total WOMAC score was reduced by 55% (p&lt;0,05; Fig 2), and EQ-5D quality of life was improved by 44% (<i>p</i>&lt;0,05). Patients from Group 2 lost only 0,88% of their body weight versus the baseline, and reduced WC by 1%, without changes in EQ-5D scores. MS lab parameters – lipid profile and glucose – did not change significantly after orlistat treatment in Group 1. Patients from Group 2 showed significant increase in total cholesterol (<i>p</i>&lt;0,05) after 6 months of dieting and exercising, revealing direct correlation between raised LDL and triglycerides levels and total WOMAC scores. CRP dropped by 23,74% (<i>p</i>&gt;0,05) in Group 1. More pronounced decrease of CRP was observed in pts losing more than 10% of their body weight (<i>p</i>=0,07). Statistically significant decrease in leptin and IL-6 levels was documented in pts with orlistat-induced significant weight loss (p&lt;0,05). <h3>Conclusions</h3> Abdominal obesity is considered to be the major component of MS and key risk factor for the development and progression of knee OA. Our study demonstrates that induced by orlistat, diet and exercise weight loss by &gt;10% improves the clinical course of KOA and patient's quality of life, reduces activity of inflammation and improves key parameters of metabolic syndrome. Therefore, KOA and MS therapeutic strategies should include pharmacotherapy of obesity in patients who fail to lose weight with the diet and physical exercise only. <h3>Disclosure of Interest</h3> None declared
Imaging and diagnostic advances for intracranial meningiomas
Authors: Raymond Y Huang, Wenya Linda Bi, Brent Griffith, Timothy J Kaufmann, Christian la Fougère, Nils Ole Schmidt, Jöerg C Tonn, Michael A Vogelbaum, Patrick Y Wen, Kenneth Aldape, Farshad Nassiri, Gelareh Zadeh, Ian F Dunn, Kenneth Aldape, Karolyn Au, Jill Barnhartz-Sloan, Wenya Linda Bi, Priscilla K Brastianos, Nicholas Butowski, Carlos Carlotti, Michael D Cusimano, Francesco DiMeco, Katharine Drummond, Ian F Dunn, Evanthia Galanis, Caterina Giannini, Roland Goldbrunner, Brent Griffith, Rintaro Hashizume, C Oliver Hanemann, Christel Herold-Mende, Craig Horbinski, Raymond Y Huang, David James, Michael D Jenkinson, Christine Jungk, Timothy J Kaufman, Boris Krischek, Daniel Lachance, Christian Lafougère, Ian Lee, Jeff C Liu, Yasin Mamatjan, Alireza Mansouri, Christian Mawrin, Michael McDermott, David Munoz, Farshad Nassiri, Houtan Noushmehr, Ho-Keung Ng, Arie Perry, Farhad Pirouzmand, Laila M Poisson, Bianca Pollo, David Raleigh, Felix Sahm, Andrea Saladino, Thomas Santarius, Christian Schichor, David Schultz, Nils O Schmidt, Warren Selman, Andrew Sloan, Julian Spears, James Snyder, Suganth Suppiah, Ghazaleh Tabatabai, Marcos Tatagiba, Daniela Tirapelli, Joerg C Tonn, Derek Tsang, Michael A Vogelbaum, Andreas von Deimling, Patrick Y Wen, Tobias Walbert, Manfred Westphal, Adriana M Workewych, Gelareh Zadeh
Journal: Neuro-Oncology (2018)

The archetypal imaging characteristics of meningiomas are among the most stereotypic of all central nervous system (CNS) tumors. In the era of plain film and ventriculography, imaging was only performed if a mass was suspected, and their results were more suggestive than definitive. Following more than a century of technological development, we can now rely on imaging to non-invasively diagnose meningioma with great confidence and precisely delineate the locations of these tumors relative to their surrounding structures to inform treatment planning. Asymptomatic meningiomas may be identified and their growth monitored over time; moreover, imaging routinely serves as an essential tool to survey tumor burden at various stages during the course of treatment, thereby providing guidance on their effectiveness or the need for further intervention. Modern radiological techniques are expanding the power of imaging from tumor detection and monitoring to include extraction of biologic information from advanced analysis of radiological parameters. These contemporary approaches have led to promising attempts to predict tumor grade and, in turn, contribute prognostic data. In this supplement article, we review important current and future aspects of imaging in the diagnosis and management of meningioma, including conventional and advanced imaging techniques using CT, MRI, and nuclear medicine.
Association of a Schizophrenia-Risk Nonsynonymous Variant With Putamen Volume in Adolescents
Authors: Qiang Luo, Qiang Chen, Wenjia Wang, Sylvane Desrivières, Erin Burke Quinlan, Tianye Jia, Christine Macare, Gabriel H. Robert, Jing Cui, Mickaël Guedj, Lena Palaniyappan, Ferath Kherif, Tobias Banaschewski, Arun L. W. Bokde, Christian Büchel, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Eric Artiges, Marie-Laure Paillère-Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Joseph H. Callicott, Venkata S. Mattay, Zdenka Pausova, Jean-François Dartigues, Christophe Tzourio, Fabrice Crivello, Karen F. Berman, Fei Li, Tomáš Paus, Daniel R. Weinberger, Robin M. Murray, Gunter Schumann, Jianfeng Feng
Journal: JAMA Psychiatry (2019)

Deviation from normal adolescent brain development precedes manifestations of many major psychiatric symptoms. Such altered developmental trajectories in adolescents may be linked to genetic risk for psychopathology.
Clonal Evolution of a Mutation in PTPRA As a Potential Cause for Resistance Against Anti-CD19 Directed Chimeric Antigen Receptor T-Cell (CAR-T) Therapy with CTL019 in DLBCL Patients
Authors: Hyatt Balke-Want, Philipp Gödel, Nima Abedpour, Martin Peifer, Peter Borchmann
Journal: Blood (2018)
SAT0688 Progressive drift of patient populations in rheumatoid arthritisclinical trials over time
Authors: A. Kerschbaumer, B. Bierbaumer, J.S. Smolen, D. Aletaha
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) is among the most intensively studied chronic inflammatory musculoskeletal diseases. Over the past two decades numerous new compounds have been tested in RA. Although the results from any new clinical trial in RA is usually interpreted in the context of existing data from previous trials, it is not clear whether trial populations are necessarily historically comparable. <h3>Objectives</h3> To understand secular trends and drifts in characteristics of patient populations enrolled in RA clinical trials. <h3>Methods</h3> We performed a systematic literature review of randomised, controlled, double-blind trials, investigating biological therapies in RA. Reports were identified using PUBMED, EMBASE and the Cochrane Library. Populations were stratified into conventional disease modifying anti-rheumatic drug (cDMARD) naïve, cDMARD inadequate responders (IR), and biological DMARD IR. The following variables at baseline were extracted from reports: swollen and tender joint counts (SJC, TJC), pain, patient and evaluator global (PGA, EGA), acute phase measures (erythrocyte sedimentation rate, ESR and C-reactive protein, CRP), as well as the Health Assessment Questionnaire Disability Index (HAQ). In addition, we obtained the year of publication and the inclusion criteria of each trial. We then performed a mixed model meta-regression of year of publication on each of the mentioned baseline variables. <h3>Results</h3> Out of 697 abstracts selected for screening, 73 studies were chosen as relevant; 3 studies with mixed populations were excluded, resulting in 70 studies included for analysis. Table 1 shows the observed medians and quartiles for the baseline characteristics. Meta-regression showed a significant decrease of SJC (β=−0.415;p≤0.001), TJC (β=−0.378;p≤0.001), and CRP (β=−0.123;p≤0.001) over the years (figure 1); for all other core set measures, there was no trend or significance. Inclusion criteria showed similar trends over time for SJC (β=−0.154,p≤0.001), TJC (β=−0.243,p≤0.001), and CRP (β=−0.065,p≤0.001). <h3>Conclusions</h3> There is a progressive drift towards lower number of swollen and tender joints and lower CRP-levels at trial entry of time, which is at least partly related to a similar trend in inclusion criteria for RA. The constancy of patient-reported outcomes suggests that the baseline activity is still perceived as similarly high. Differences in overall baseline inflammatory activity may pose a challenge for comparing newer with older trial results. <h3>Disclosure of Interest</h3> None declared
Abstract 14993: Drug Transporter Polymorphisms and Age Predict Circulating Atorvastatin and Rosuvastatin Concentration in Patients
Authors: Marianne K DeGorter, Rommel G Tirona, Ute I Schwarz, Yun-Hee Choi, Kathryn Myers, Neville Suskin, Guangyong Zou, George K Dresser, Robert A Hegele, Richard B Kim
Journal: Circulation (2012)

Background: Statins are effective in reducing risk for major cardiovascular events, and are prescribed to nearly 10% of adults in developed countries. A significant barrier to statin therapy is mus...
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1−CD8+ Tumor-Infiltrating T Cells
Authors: Sema Kurtulus, Asaf Madi, Giulia Escobar, Max Klapholz, Jackson Nyman, Elena Christian, Mathias Pawlak, Danielle Dionne, Junrong Xia, Orit Rozenblatt-Rosen, Vijay K. Kuchroo, Aviv Regev, Ana C. Anderson
Journal: Immunity (2019)
SAT0371 Factors associated with allopurinol adherence and treatment outcome among gout patients
Authors: S. Asaiphanit, P. Narongroeknawin
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> A serum uric acid (SUA) level of &lt;6.0 mg/dL has been widely accepted as the therapeutic target for patients with gout. Recent studies implicate allopurinol nonadherence as a major barrier to achieving this target. However, factors that could affect this medication adherence are not clearly identified. <h3>Objectives</h3> To identify factors associated with allopurinol adherence and SUA goal attainment in gout patients. <h3>Methods</h3> This study identified patients aged 18 years or older with a diagnosis of gout by 1977 ARA classification criteria for gout, received at least 1 month of allopurinol, and attended out-patient clinics of Phramongkutklao hospital from <sup>Jul 2016</sup>-Sep 2017. Allopurinol adherence was defined as Medication Taking Behaviour for Thai patient (MTB-Thai) scores&gt;21 points. Patient characteristics, comorbidities, concomitant medications, prescriber specialty, number of gout attack and SUA were examined. Multivariate logistic regression was used to examine factors associated with allopurinol adherence and SUA target, defined as SUA &lt;6.0 mg/dL. <h3>Results</h3> A total of 226 patients with gout was included. Approximately half of patients (43.4%) were adherent, whereas only one-third of them achieved SUA target (29.2%). Factors associated with allopurinol adherence in the multivariate analysis included disease duration (&gt;1 year) (odds ratio [OR] 0.1, 95% confident interval [CI]: 0.05–0.21), history of gout attack (&gt;2 times/year) (OR 0.14, 95% CI: 0.08–0.27), and prescriber specialty (rheumatologist) (OR 2.64, 95% CI: 1.28–5.43). Factors associated achieved SUA goal in the multivariable analysis included history of gout attack (&gt;2 times/year) (OR 0.21, 95% CI: 0.1–0.42), prescriber specialty (rheumatologist) (OR 2.01, 95% CI: 1.31–4.13), allopurinol dose escalation (OR 2.11, 95% CI: 1.17–3.79), current allopurinol dosage (&gt;100 mg/day) (OR 2.02, 95% CI: 1.11–3.65). and allopurinol adherence (OR 13.6, 95% CI: 6.52–28.39). <h3>Conclusions</h3> Among patients with gout receiving allopurinol in our study, 70.8% did not reach the SUA goal and 56.6% of patients were non-adherent. Allopurinol adherence was strongly associated with SUA goal attainment. The only modifiable factor associated with allopurinol adherence was prescriber specialty, whereas, modifiable factors associated with SUA goal attainment were prescriber specialty, allopurinol dose escalation, and current allopurinol dosage. Appropriate dose escalation and rheumatology referral could be important factors to consider in efforts aimed at optimising gout treatment outcomes. <h3>Disclosure of Interest</h3> None declared