tbuckley/cabot-search huggingface dataset:
Preserving Civility in Vaccine Policy Discourse
Authors: Gregory A. Poland, Jon C. Tilburt, Edgar K. Marcuse
Journal: JAMA (2019)

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PMMA-Fe<sub>3</sub>O<sub>4</sub> for internal mechanical support and magnetic thermal ablation of bone tumors
Authors: Kexiao Yu, Bing Liang, Yuanyi Zheng, Agata Exner, Michael Kolios, Tiantian Xu, Dajing Guo, Xiaojun Cai, Zhigang Wang, Haitao Ran, Lei Chu, Zhongliang Deng
Journal: Theranostics (2019)

Background: Minimally invasive modalities are of great interest in the field of treating bone tumors. However, providing reliable mechanical support and fast killing of tumor cells to achieve rapid recovery of physical function is still challenging in clinical works. Methods: A material with two functions, mechanical support and magnetic thermal ablation, was developed from Fe3O4 nanoparticles (NPs) distributed in a polymethylmethacrylate (PMMA) bone cement. The mechanical properties and efficiency of magnetic field-induced thermal ablation were systematically and successfully evaluated in vitro and ex vivo. CT images and pathological examination were successfully applied to evaluate therapeutic efficacy with a rabbit bone tumor model. Biosafety evaluation was performed with a rabbit in vivo, and a cytotoxicity test was performed in vitro. Results: An NP content of 6% Fe3O4 (PMMA-6% Fe3O4, mFe: 0.01 g) gave the most suitable performance for in vivo study. At the 56-day follow-up after treatment, bone tumors were ablated without obvious side effects. The pathological examination and new bone formation in CT images clearly illustrate that the bone tumors were completely eliminated. Correspondingly, after treatment, the tendency of bone tumors toward metastasis significantly decreased. Moreover, with well-designed mechanical properties, PMMA-6%Fe3O4 implantation endowed tumor-bearing rabbit legs with excellent bio-mimic bone structure and internal support. Biosafety evaluation did not induce an increase or decrease in the immune response, and major functional parameters were all at normal levels. Conclusion: We have presented a novel, highly efficient and minimally invasive approach for complete bone tumor regression and bone defect repair by magnetic thermal ablation based on PMMA containing Fe3O4 NPs; this approach shows excellent heating ability for rabbit VX2 tibial plateau tumor ablation upon exposure to an alternating magnetic field (AMF) and provides mechanical support for bone repair. The new and powerful dual-function implant is a promising minimally invasive agent for the treatment of bone tumors and has good clinical translation potential.
Comparative Effectiveness of Daratumumab Monotherapy Versus a Real-World Historical Control from the Czech Republic in Heavily Pretreated and Highly Refractory Multiple Myeloma Patients
Authors: Roman Hájek, Tomas Jelinek, Vladimir Maisnar, Ludek Pour, Ivan Spicka, Jiri Minarik, Evzen Gregora, Petr Kessler, Michal Sykora, Hana Frankova, Dagmar Adamova, Marek Wróbel, Peter Mikula, Jiri Jarkovsky, Xenia Gatopoulou, Sarka Vesela, Joris Diels, Hervé Besson, Lucie Brozova, Tetsuro Ito
Journal: Blood (2016)
FRI0055 AN EQUATION FOR ESTIMATED CARDIORESPIRATORY FITNESS IN RHEUMATOID ARTHRITIS PATIENTS IS NEEDED
Authors: Marthe Halsan Liff, Mari Hoff, Vibeke Videm
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> RA patients are deconditioned and on average have decreased cardiorespiratory fitness (CRF, peak oxygen uptake) compared to the general population (1). This may contribute to an increased risk of cardiovascular disease (CVD). Because CRF is associated with cardiovascular health, it is important to assess. For the general population, various equations exist for estimation of CRF (eCRF) without the need of a resource-intensive cardiopulmonary exercise test. <h3>Objectives</h3> Compare eCRF of people without RA to eCRF of RA patients, using recognized equations for eCRF (2,3) based on gender, age, resting heart rate, waist circumference and self-reported physical activity. <h3>Methods</h3> Among participants with self-reported RA in the second and third surveys of the Norwegian population-based Nord-Trøndelag Health Study (HUNT2 and 3)(4), RA patients were identified from hospital case files using standardized diagnostic criteria (5). The mean eCRF of participants with and without RA were calculated and the 95% confidence intervals (CI) compared. <h3>Conclusion</h3> The eCRF CIs of RA patients and participants without RA were overlapping in all age categories except for men aged 60-69 years in HUNT 3 (Table1). This is contradictory to previous findings where RA patients were deconditioned compared to healthy controls (1). A probable explanation is that equations for eCRF were developed from healthy populations, and therefore overestimate eCRF in RA patients. For better CVD risk management including CRF as an important risk factor, an equation for eCRF developed specifically for RA patients is needed. <h3>References</h3> [1] Munsterman T, et al. BMC Musculoskelet Disord. 2012;13:202. [2] Nes BM, et al. Med Sci Sports Exerc. 2014;46(6):1159-65. [3] Nauman J, et al. Mayo Clin Proc. 2017;92(2):218-27. [4] Krokstad S, et al. Int J Epidemiol. 2013;42(4):968-77. [5] Videm V, et al. J Rheumatol. 2017;44(8):1134-41 <h3>Disclosure of Interests</h3> None declared
PS1469 IL28B GENE POLYMORPHISMS INFLUENCE ON THE RESPONSIVENESS AND TOLERABILITY OF IFN‐Α IN PATIENTS WITH MPN
Authors: I. Olkhovskiy∗, M. Stolyar, A. Gorbenko, D. Lagutinskaya, E. Dunaeva, K. Mironov, G. Shipulin, T. Olkhovik, M. Mikhalev, E. Vasiliev, M. Smelyanskaya, A. Hazieva
Journal: HemaSphere (2019)

Background: Interferon‐α (IFN‐α) provides several benefits to myeloproliferative neoplasms (MPNs) patients and leads 35% of its experienced a good molecular response. Both newly diagnosed and previously treated patients with polycythemia vera (PV) exhibit high hematologic response rates, and some of these patients achieve molecular responses [Kiladjian J‐J., et al., 2016]. Nevertheless, IFN‐α therapy is often accompanied by serious side effects, which forces some patients to refuse treatment. Only one scientific team [Lindgren M., et al., 2012, 2018] previously published data demonstrating the effect of IL28B gene polymorphisms on the success of interferon therapy in MPNs. Aims: Evaluate the prognostic impact of IL28B rs12979860 and rs8099917 on IFN‐α treatment response and toxicity in patients with MPNs. Methods: 35 patients were investigated: 18 with polycythemia vera, 12 with essential thrombocythemia and 5 with primary myelofibrosis. All patients were treated with IFN‐α (three times weekly). DNA from whole blood samples was isolated using «DNAsorb‐B» (Central Research Institute for Epidemiology, Russia). The rs12979860 and rs8099917 SNPs genotyping was determined by pyrosequencing on a PyroMark Q24 instrument. Allele burden JAK2 V617F was determined using «Myeloscreen JAK2» («Formula of gene Ltd», Russia). Hematologic response was evaluated using the European Leukemia Net criteria. The quantitative values are given as a median and 25% and 75% percentiles. Results: The JAK2 V617F allele burden after 60 months of IFN‐α therapy was significantly reduced in samples of patients with polycythemia vera in the presence of a “strong” TT/CC variant of the haplotype IL28B (13; 8.4–24.4) compared with other variants of polymorphism of these gene (57; 44,3–67,0). The average duration of therapy to failure due to side effects of IFN‐α was also 2–3 times shorter ( p &lt; 0.05) in patients with a TT/CC haplotype. The therapeutic impact of IFN‐α in patients with MPN involve IL28B signaling pathways. This is the second independent confirmation of the data by Lindgren et al. Summary/Conclusion: Genotype evaluation of IL28B can be useful for predicting the effectiveness of interferon therapy in MPNs. image
PS1298 TISSUE IRON DISTRIBUTION IN PATIENTS WITH LOW‐RISK MDS
Authors: R. Grosse, A.M. Asemissen, C.G. Ganster, J. Starekova, P. Schafhausen, B. Schoennagel, P. Nielsen, J. Yamamura, D. Haase, R. Fischer
Journal: HemaSphere (2019)

Background: Iron accumulation occurs in MDS patients by upregulated iron absorption due to ineffective erythropoiesis with decreased hepcidin levels ( Santini et al, 2011 ) and by chronic blood transfusion therapy. Elevated liver iron concentration (LIC) is regularly found in transfusion dependent patients. Abnormal cardiac iron (50–1) was observed in few studies and severe cardiac iron overload was almost not present although cardiac death appeared in 8% of deceased patients ( Nachtkamp et al, 2016 ). Little is known about corresponding pancreatic iron and iron accumulation in the bone marrow. The release of NTBI in the bone marrow may directly affect hematopoiesis by oxidative stress ( Porter et al, 2016 ). Aims: To compare the relationship of iron concentration and fat content in different organs in low ‐ risk MDS patients. Methods: We studied the iron accumulation in bone marrow, liver, spleen, pancreas and septal heart muscle in 14 mainly low‐risk MDS patients (age 39–87 y), partly transfused and chelated. Tissue iron concentration and fat content were assessed by magnetic resonance imaging (MRI ‐ R2 ∗ ) with 3D data acquisition at 3 Tesla using chemical shift relaxometry ( Pfeifer et al, 2015 ). Results: About 50% of patients showed iron overload in the spleen, pancreas and vertebral bone marrow (VBM). Mean LIC (±SD) was found as 1.709 ± 0.914 mg/g liver (10.3 ± 5.5 mg/g dry weight ). Patients with iron overload in the pancreas showed as well abnormal pancreatic fat contents (11–32%) and fasting glucose values (101–186 mg/dL). As expected, septal cardiac iron was normal for all patients. Bone marrow (VBM) iron was elevated in 8/14 patients (R2 ∗ = 149–330 s −1 ) with the highest R2 ∗ in a non‐chelated patient. Summary/Conclusion: The feasibility of multi‐organ iron and fat measurements by MRI in heart, liver, spleen, pancreas and bone marrow was shown in a small group of elderly MDS patients within a reasonable scan time (30 min). The iron concentration and fat content in different organs will contribute further information about disease process in low ‐ risk MDS patients, as well as success of iron chelation therapy.
AB0660 SEXUAL HEALTH IMPAIRMENT IN WOMEN WITH IDIOPATHIC INFLAMMATORY MYOPATHIES
Authors: Barbora Heřmánková, Maja Špiritović, Hana Smucrova, Sabina Oreska, Hana Štorkánová, Kristyna Bubova, Karel Pavelka, Jiří Vencovský, Ladislav Šenolt, Heřman Mann, Michal Tomčík
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Idiopathic inflammatory myopathies (IIM) are a group of disorders characterized by skeletal muscle inflammation that can cause functional impairment including sexual dysfunction. <h3>Objectives:</h3> To assess sexual function, pelvic floor function and sexual quality of life of women with IIM compared to age-/sex-matched healthy controls (HC). To subanalyze sexual function in sexually active individuals. <h3>Methods:</h3> In total 27 women with IIM [mean age: 54.2, disease duration: 7.3 years, dermatomyositis (DM, 10)/polymyositis (PM, 13)/necrotizing myopathy (IMNM, 3)/inclusion body myositis (IBM, 1)], who fulfilled the Bohan/Peter 1975 criteria for DM/PM, and 27 healthy women (mean age: 54.2) filled in 11 well-established and validated questionnaires assessing sexual function, pelvic floor function, quality of life, fatigue, physical activity and depression. Data are presented as mean±SEM. <h3>Results:</h3> Compared to HC, patients with IIM had significantly higher prevalence and greater severity of sexual impairment (FSFI, BISF-W), dysfunction of pelvic floor (PISQ-12), and worse sexual quality of life (SQoL-F) (table 1). There were no significant differences in sexual function between PM and DM. Even sexually active IIM patients reported significantly greater sexual health impairment compared to sexually active HC. Sexual health impairment in IIM was associated with laboratory markers of disease activity, health status, physical activity, fatigue and depression (table 2). <h3>Conclusion:</h3> Women with IIM reported significantly impaired sexual function, sexual quality of life and pelvic floor function than age-matched HC. Worse scores in IIM were associated with disease activity/health status, physical activity, fatigue and depression. <h3>Acknowledgement:</h3> Supported by aZV-16-33574A, MHCR 023728. <h3>Disclosure of interests:</h3> Barbora Heřmánková: None declared, Maja Špiritović: None declared, Hana Smucrova: None declared, Sabina Oreska: None declared, Hana Štorkánová: None declared, Kristyna Bubova: None declared, Karel Pavelka: None declared, Jiří Vencovský Consultant for: Samsung, Speakers bureau: abbVie, Novartis, Pfizer, Sanofi, Eli Lilly, Biogen, UCB, MSD, Werfen, Roche, Ladislav Šenolt Grant/research support from: abbVie, Consultant for: abbVie, Bristol-Myers Squibb, Celgene Corporation, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, amgen, Takeda, Speakers bureau: abbVie, amgen, Bristol-Myers Squibb, Celgene Corporation, Eli Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Roche, UCB, Heřman Mann Consultant for: Pfizer, Eli Lilly, Sanofi, Speakers bureau: abbVie, Roche, Pfizer, MSD, Eli Lilly, Sanofi, Michal Tomčík: None declared
Abstract 14148: Patient Characteristics and Predictors of Off-Label versus Standard Dosing of Direct Oral Anticoagulants in Medicare Beneficiaries With Atrial Fibrillation
Authors: Alexandros Briasoulis, Yubo Gao, Mary Vaughan Sarrazin
Journal: Circulation (2018)

Introduction: Off-label dosing (OD) of direct oral anticoagulants (DOACs) may lead to increased risk for adverse events. We examined a large, community-based sample of patients with atrial fibrilla...
Assessment of Mortality and Smoking Rates Before and After Reduction in Community-wide Prevention Programs in Rural Maine
Authors: Daniel K. Onion, Roderick E. Prior, N. Burgess Record, Sandra S. Record, Gerald R. Cayer, Christopher I. Amos, Thomas A. Pearson
Journal: JAMA Network Open (2019)

<h3>Importance</h3> It is unclear whether effective population-wide interventions that reduce risk factors and improve health result in sustained benefits to a community's health. If benefits do persist after a program is ended, interventions could be brief rather than maintained long term. <h3>Objective</h3> To measure mortality and smoking rates in a rural community over decades before, during, and after prevention program reductions. <h3>Design, Setting, and Participants</h3> This cross-sectional study compared smoking and mortality rates in a rural Maine county with other Maine counties over time by 5-year intervals. Multiple changes occurred between 2001 and 2015 in the physiological and behavioral risk factor reduction programs offered in the county. They included reductions in leadership, staff, institutional resources, data monitoring, and the programs themselves. Data were analyzed from May 2018 to March 2019. <h3>Intervention</h3> Previous multifaceted interventions and outcome monitoring were withdrawn or diminished in the past decade. <h3>Main Outcomes and Measures</h3> Smoking and age-adjusted mortality rates vs household income. <h3>Results</h3> Reduced mortality rates in Franklin County in 1986 to 2005 reverted to those predicted by household incomes, relative to other Maine counties, by 2006 to 2015 (1986-1990 T score = −2.86 [<i>P</i> = .01] and 2001-2005 T score = −3.00 [<i>P</i> = .01] to 2006 to 2010 T score = −0.43 [<i>P</i> = .67] and 2011-2015 T score = −0.72 [<i>P</i> = .48]). Analysis of County Health Rankings data from 2010 to 2018 also showed that Franklin County’s outcomes have reverted to no better than predicted by socioeconomic status. The county’s T scores increased from −3.62 (<i>P</i> = .003) in 2010 to −0.41 (<i>P</i> = .69) in 2015 to 0.13 (<i>P</i> = .90) in 2018. Statewide association of income with mortality by analyses of variance showed that the<i>R</i><sup>2</sup>values have increased from the decades preceding 2000 (1976-1980,<i>R</i><sup>2</sup> = 0.21;<i>P</i> = .08; 1986-1990,<i>R</i><sup>2</sup> = 0.32;<i>P</i> = .02) to 2006 to 2010 (<i>R</i><sup>2</sup> = 0.73;<i>P</i> &lt; .001) and 2011 to 2015 (<i>R</i><sup>2</sup> = 0.70;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> This study suggests that gains associated with population health interventions may be lost when the interventions are reduced. Adjusting outcome measures for socioeconomic status may allow quicker and more sensitive monitoring of intervention adequacy and success. The increasing trend of age-adjusted mortality in Maine and nationally to correlate inversely with incomes may warrant further community interventions, especially for poorer populations.
PB2090 AZACYTIDINE BEFORE ALLOGENEIC STEM CELL TRANSPLANTATION IS INFERIOR TO HD/ARA-C WITH RESPECT TO RELAPSE FOLLOWING TRANSPLANTATION
Authors: H. Demiroglu, M. Okay, R. Ciftciler, E. Aladag, O. Gul, Y. Buyukasik, H. Goker
Journal: HemaSphere (2019)

Background: Myelodysplastic syndrome (MDS) is characterized as a heterogeneous group of clonal myeloid malignancies. Allogeneic stem cell transplantation (ASCT) is the only curative treatment option in MDS. The International Prognostic Scoring System (IPSS) (1) and IPSS-R (2) were generated for MDS prognostic scores. Azacytidine (AZA) is a DNA hypomethylating agent which is used in intermediate 2 and high IPSS-R MDS before ASCT. AZA prior to ASCT is better than conventional chemotherapy before ASCT in terms of side effects in MDS and acute myeloid leukemia (AML) with low blast counts (3). However, AZA prior to ASCT may increase relapse after ASCT in MDS/AML. Aims: In this study, we aimed to clarify the effect of AZA before ASCT on MDS/AML patients after ASCT. Methods This study was designed in a retrospective manner. 22 age and sex matched MDS/AML patients who underwent ASCT were evaluated. All MDS patients had high or intermediate-2 IPSS-R risk score. The categorical and continuous data were compared with Chi-square and independent sample t-test. The statistical significance threshold was considered as p <0.05. Results: 22 patients were included in the study. AZA group (n = 11) and non-AZA groups’ (n = 11) age and sex parameters were matched. Hemoglobin, neutrophil and platelet counts of two groups at diagnosis were shown in Table 1. Patients in the AZA group received at least 3 cycles of AZA treatment (75 mg/m2/day for 7 days). Patients in the non-AZA group received at least 2 cycles of conventional high intensity treatment. Complete response (CR) was achieved in 3 and 9 patients, stable disease (SD) in 8 and 2 patients before ASCT in the AZA and non-AZA groups, respectively. Myeloablative and reduced intensity conditioning regimen was used in 2 and 9 patients (non-AZA group), 4 and 7 patients (AZA group), respectively. The 1-year OS rates were 72.7% and not reached in non-AZA and AZA group, respectively (p = 0.1). The 1-year DFS rates were 71.6% and 46.2% in non-AZA group and AZA group, respectively (p = 0.09) (Figure 2). 4 patients died in the non-AZA group. Causes of death were relapse (3 patients) and infectious complication (1 patient).Summary/Conclusion: In the literature, AZA can be used as a ‘bridge’ treatment to ASCT, because of low adverse effects (3). According to the results of this retrospective study, we think that higher intensity treatment is superior to AZA in terms of relapse and DFS after transplantation. Prospective controlled studies in larger groups of patients are needed in order to further elucidate whether higher intensity treatment protocols should be given in MDS patients before ASCT to prevent relapse.
FRI0264 ADVERSE EVENTS DUE TO HIGH DOSE GLUCOCORTICOIDS – LESSONS FROM ANCA-ASSOCIATED VASCULITIS AND OTHER INFLAMMATORY DISEASES
Authors: Peter Rutherford, Dieter Götte
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> High dose glucocorticoids (GCs) are a component of induction remission and maintenance regimes in ANCA-associated vasculitis (AAV) and are used in other inflammatory disorders. The adverse event (AE) profile of GC is well known and in AAV is believed to link to early mortality risk from infection as well as long term organ/tissue damage. However, it is known GC AE reporting is incomplete and EULAR made specific recommendations for such reporting in clinical trials (Van der Goes 2010). <h3>Objectives</h3> This systematic literature review aimed to examine AE rates and outcomes related to high dose GC use in AAV and to quantify AE risk in terms of GC dose and duration. <h3>Methods</h3> A systematic literature review was performed of studies published between 1 Jan 2007 and 30 January 2018. Data on GC-related AEs (defined as any untoward medical occurrence) and serious AEs (defined in European Medicines Agency CPMP/ICH/377/95) which threaten life or function were extracted from identified trials. The initial AAV search demonstrated incomplete GC data collection compared to EULAR recommendations in most AAV studies so the search strategy was extended to include other inflammatory disorders in which similar GC regimes and doses are used namely systemic lupus erythematosus, glomerulonephritis, pemphigus and giant cell arteritis. <h3>Results</h3> Three hundred and eleven studies of these 5 conditions were identified in which GC-related AEs were published. 38 studies were selected for a detailed AE analysis on the basis of their inclusion of full description of GC regime, actual delivered GC dose and patient exposure. Of the 62,630 patients enrolled in the 38 studies, 35,587 were exposed to GCs. 21 studies reported serious AEs, while 17 studies reported AEs only. The most common serious AEs related to specific organ damage - particularly musculoskeletal, ocular and neuropsychiatric - but mortality and infection were also observed. The most common AEs were metabolic conditions, with diabetes related events comprising 72% of the metabolic AEs, and weight gain comprising 15%. <h3>Conclusion</h3> GC-related AE reporting in clinical studies of high dose GCs could be improved. Serious AEs including organ damage, infection and mortality were reported and both total GC dose and therapy duration are important risk factors mortality and infection. Metabolic and musculoskeletal events are a particular patient burden. New therapeutic options for AAV and other disorders should aim to reduce this AE profile. <h3>References</h3> [1] Van der Goes, et al. Ann Rheum Dis 2010; 69: 1913-19 <h3>Acknowledgement</h3> This work was supported by Vifor Pharma <h3>Disclosure of Interests</h3> Peter Rutherford Employee of: Vifor Pharma, Dieter Götte Employee of: Vifor Pharma