tbuckley/cabot-search huggingface dataset:
AB0815 Health related quality of life in patients with systemic sclerosis treated with two different intravenous iloprost regimens
Authors: T. Schioppo, L. Scalone, P. Cozzolino, L. Mantovani, G. Cesana, O. De Lucia, A. Murgo, F. Ingegnoli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In systemic sclerosis (SSc), Raynaud's phenomenon (RP) and digital ulcers (DU) can decrease health related quality of life (HRQoL). Intravenous (IV) iloprost (ILO) is administered for RP, after oral therapy failure, and DU healing. HRQoL is considered fundamental to assess the impact of the disease and therapy on patients: EQ-5D-5L has been satisfactory used to assess the general HRQoL in SSc. <h3>Objectives</h3> Aim of our study was to estimate HRQoL in SSc patients treated with two different IV ILO regimens and in patients not requiring IV ILO. <h3>Methods</h3> This was a monocentric, prospective, pragmatic and non-randomised study. Enrolled SSc patients were divided into 3 groups: no IV ILO (group A), IV ILO once monthly (B) or IV ILO for 5 consecutive days every 3 months (C). HRQoL was assessed using EQ-5D-5L through a telephone interview. Group A patients were evaluated at baseline and after 3 months; group B 2 days before each infusion and 2 weeks after each infusion; group C 2 days before each therapy cycle, and after 2 and 6 weeks after the first cycle of therapy. The EQ-5D-5L describes HRQoL, measures the overall health state with a 0–100 visual analogue scale (VAS) and values health with a utility index. Multiple regression analyses was performed to calculate VAS and mean utility index in each group (confounders: age, sex, treatment group, baseline utility or VAS score, average outdoor temperature the week before the evaluation at patient's place of residence, RP VAS, disease duration and modified Rodnan skin score). <h3>Results</h3> 96 patients were enrolled: 52 in group A, 24 in B, and 20 in C. Of these 35, 21 and 16 completed the study respectively. Utility and VAS score at the end of the three months, as adjusted for the possible confounders, were not statistically different in the three groups. <h3>Conclusions</h3> Utility and VAS, at 3 months follow-up, were not different in the 3 groups as if IV ILO was able to make patients requiring IV ILO as similar as patients not requiring IV ILO. Moreover, in this model there was no difference between the two ILO regimens (1 days monthly vs 5 every 3 months). These results suggest that our therapeutic approach, based on various criteria such as demographic, clinical characteristics, logistic aspects and patients' preferences, allows to reach or to maintain HRQoL at comparable levels between the three groups considered. <h3>Acknowledgements</h3> Meteo Operations Italia SrL – Centro Epson Meteo for temperature data. <h3>Disclosure of Interest</h3> None declared
FRI0015 Treating rheumatoid arthritis to target: is low disease activity good enough?
Authors: E. Nikiphorou, S. Norton, A. Young, L. Carpenter, J. Dixey, D. Walsh, P. Kiely
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Treat-to-target (T2T) principles in rheumatoid arthritis (RA) are now widely recognised as effective in achieving optimal disease outcomes. <h3>Objectives</h3> To examine for differences in outcomes between low (LDAS) and remission (RDAS) disease activity score (DAS) categories, addressing the question: is LDAS a ‘good enough’ treatment target in RA? <h3>Methods</h3> Data from two consecutive UK multi-centre RA inception cohorts with similar design were used: the Early RA Study (ERAS) and Early RA Network (ERAN). Recruitment figures/median follow up for ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years) respectively. Standard demographic and clinical variables were recorded at baseline and then annually until the end of study follow up. Disease activity was categorised by mean DAS28 score between years 1–5 as remission [mRDAS &lt;2.6] or low [mLDAS 2.6–3.2]; as sustained low/remission DAS (sLDAS/sRDAS) based on DAS persisting in each of the two categories at years 1–2 and as Boolean remission (years 1–2). Change in HAQ and SF36 (physical [PCS] and mental [MCS] components) for each disease activity category were modelled using linear mixed models with time incorporated as a linear spline with change-point at 12 months. Year of onset, age, gender and use of steroids or conventional DMARDS at first visit were included as covariates. <h3>Results</h3> Out of 2701 patients, 468 (17%) were in mRDAS, 284 (11%) in mLDAS in the first five years of disease. Lower proportions had achieved sRDAS (8%), sLDAS (6%) and Boolean (2%) remission. Mean age was similar across categories; more women were in low vs remission DAS. Compared to mLDAS or sLDAS, inflammatory markers, DAS, functional (HAQ, PCS) and mental (MCS) scores tended to be better in the mRDAs, sRDAS or Boolean remission categories (figure 1). Significant differences (p&lt;0.05) were noted between the mRDAS and mLDAS between years 1–5 for all outcomes; for sRDAS compared to sLDAS, the difference was significant at one year but not by five years. <h3>Conclusions</h3> The results demonstrate striking differences between remission and low DAS categories, suggesting worse functional and SF36 outcomes over time in the low DAS categories. This supports that remission should be the primary T2T goal in in RA. <h3>Disclosure of Interest</h3> None declared
Combination of KS119W with other antitumor agents for the treatment of murine and human tumor xenografts in mice
Authors: Qin Wang, Louis Bai Song, Lanzhen Liu, Xu Kevin Lin, Michael F. Belcourt, Ala Nassar, Caroline Clairmont, Ivan King, Li Mou Zheng
Journal: Cancer Research (2005)

1390  We have previously demonstrated that KS119W, a novel hypoxia-selective anticancer agent, possesses antitumor activities against murine EMT-6 and human H460 tumors in mice. Based on these results, we predicted that combination therapy of KS119W and a chemotherapeutic agent that targets the normoxic tumor cells would produce an additive or synergistic effect. The present study was undertaken to evaluate this strategy by using KS119W at doses below the maximum tolerated dose in combination with non-toxic doses of cyclophosphamide (CTX) or gemcitabine (GEM) against murine EMT-6 and human H460 tumors in nude mice. Treatments began when the size of the tumors reached approximately 150 mm3. In the H460 tumor model, animals were treated intraperitoneally (ip) with 180-240mg/kg per dose of KS119W, on days 1, 7, 14, and 22. CTX was given at 100mg/kg, ip, on the same days. In a different experiment, GEM was given at 75-120mg/kg, on days 1, 7, 14 and 21. CTX or GEM was given two hours after KS119W dosing. KS119W alone inhibited H460 tumor growth by 78.2% (p=0.006) whereas CTX produced 54.5% inhibition (p=0.039). The combination treatment of KS119W and CTX resulted in 89.8% inhibitory effects (p=0.003), comparing to untreated controls. In the EMT-6 model, treatment of KS119W at 97mg/kg (7 daily doses) inhibited tumor growth by 58.5%. CTX at 100mg/kg, ip, once per week for 4 weeks, generated a negligible tumor growth inhibition. Combination treatment of KS119W and CTX inhibited tumor growth by 91.8% (p=0.0001, comparing to untreated controls). Similar antitumor effects were also observed in animals treated with a combination of KS119W and GEM. Immunohistochemical studies were also used to evaluate the effects of KS119W in tumors. KS119W profoundly reduced tumor cell proliferation around hypoxic areas. KS119W enhanced the cytotoxic effect of GEM and significantly increased the necrotic area. These results show that KS119W, in combination with conventional antitumor agents, could present a therapeutic advantage for future cancer therapy.
Inhibition of Lysine-Specific Demethylase 1A (LSD1) Supports Human HSCs in Culture By Preserving Their Immature State
Authors: Agatheeswaran Subramaniam, Mehrnaz Safaee Talkhoncheh, Kristijonas Zemaitis, Shubhranshu Debnath, Jun Chen, Mayur Jain, Roman Galeev, Jonas Larsson
Journal: Blood (2018)
The active metabolite of the TLR7 agonist prodrug ANA773 activates anti-tumor activity by natural killer cells
Authors: Joyce Tan, Tim Harding, Simon Fletcher, Sara Fish, Greg Haley, Joe Lennox, Eric Rueden, Devron Averett, James Appleman
Journal: Cancer Research (2007)

3556  The innate immune response provides the first line of defense against tumor cells by inducing a cascade of immunomodulatory events that includes the secretion of cytokines and the stimulation of natural killer (NK) cells. NK cells mediate anti-tumor activity by two different mechanisms. First, NK cells direct the lysis of tumor cells through the secretion of cytotoxic granules and promote apoptosis through the production of IFN-γ. The latter also increases the anti-tumor response of other immune cells. Second, NK cells also recognize and kill transformed cells through antibody-dependent cell-mediated cytotoxicity (ADCC). NK cells are activated by diverse signals, including type I interferons (IFN). Large amounts of type I IFN are produced by plasmacytoid dendritic cells (pDCs) upon engagement of the pattern recognition receptor toll-like receptor 7 (TLR7). The natural ligand for TLR7 is single stranded RNA, although a variety of small molecule agonists have also been discovered. This study investigated the effects of such a low molecular weight TLR7 agonist on human NK cell activity.  ANA773 is an oral prodrug of a selective TLR7 agonist. This biologically active metabolite of ANA773 induced the secretion of IFN-α and various other cytokines from human peripheral blood mononuclear cells (PBMC) cultured in vitro. Cytokine levels were also elevated in the plasma of treated primates. Human PBMC stimulated with the active metabolite of ANA773 augmented NK cell cytotoxicity and cytokine secretion against both K562 erythroleukemic cells and transformed B cell lines. These effects were shown to be dependent on the presence of type I IFN, confirming the importance of IFN-α in mediating NK responses to TLR7 agonists. In addition to enhancing NK activation through the direct recognition of tumor cells, this small molecule TLR7 agonist also enhanced ADCC; treatment of human PBMC with the active metabolite augmented cytolysis of rituximab (anti-CD20) bound, CD20-expressing B cell tumor lines.  Thus, the active metabolite of ANA773 promotes NK cell mediated anti-tumor response by promoting cytokine secretion, cytolysis of tumor cells, and antibody-dependent tumor cell lysis. These data indicate that TLR7 is an attractive therapeutic target for the treatment of tumor malignancies.
THU0591 Serum 25 oh vitamin d in paediatric systemic lupus erythematosus: in relation to disease activity, duration and bone mineral density
Authors: M.H. Abu-Zaid, H.H. Abdelnabi, A.M. El-Barbary
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Vitamin D has immunomodulatory effects and is commonly deficient in Paediatric SLE (pSLE) so associated with the disease activity and low bone density<sup>1,2</sup> <h3>Objectives</h3> To assess serum level of 25(OH)vitamin D in paediatric lupus patients and correlate it with disease activity, duration and bone density <h3>Methods</h3> A retrospective cohort study conducted on 90 patients with pSLE classified into three groups (30 patients in each) according to disease activity and duration. Group I (Initial active patients), group II (relapsing active patients) and group III (inactive patients), compared with 60 healthy children as controls (group IV). Disease and drugs duration, present steroid dose, medications' history and SLEADI for disease activity were evaluated. CBC, serum C3, C4, 24 hour urinary proteins, anti-dsDNA, Ca, P, PTH, 25(OH) D levels and lumbar spine BMD Z score were measured. Vitamin D levels were correlated with clinical, laboratory and radiological parameters. <h3>Results</h3> There were significant differences in mean 25(OH) D concentration between the patients' groups (I=15.37±5.72, II=17.70±4.88, III=26.98±6.59 ng/ml) and controls=35.90±9.66 ng/ml (p&lt;0.05), with significant difference between active groups (I, II) and inactive group III (p&lt;0.05). Lumbar spine Z-score was significantly different between groups (I: −0.39±0.81, II: −1.58±1.12, III: −0.99±0.89, IV: 0.58±0.71). There were significant negative correlations between serum 25(OH) D and SLEDAI (r −0.545, p 0.001), steroid dose (r −0.561, p 0.001), anti-dsDNA (r −0.685, p 0.006), 24 hr-proteinuria (r −0.738, p 0.001) and PTH (r −0.335, p 0.001), significant positive correlations between 25(OH) D and C3 (r 0.617, p 0.001),C4 (r 0.544, p 0.001) and serum Ca (r 0.424, p 0.001) with non-significant correlations between 25(OH) D and disease duration, steroids' duration, serum P and Z scores (p&gt;0.05). <h3>Conclusions</h3> Vitamin D deficiency is common in pSLE and is considered a risk factor for the disease occurrence as it is correlated significantly with the disease activity not duration. <h3>References</h3> [1] Vojinovic J, Cimaz R. Pediatric Vitamin D update for the pediatric rheumatologists. Rheumatol2015;13:18. [2] Stagi S, Cavalli L, Bertini F, et al. Vitamin D levels in children, adolescents, and young adults with juvenile-onset systemic lupus erythematosus: a cross-sectional study Lupus2014; 23:1059–1065. <h3>Disclosure of Interest</h3> None declared
Oral Azacitidine (CC-486) Plus R-CHOP in Patients with High-Risk or Previously Untreated Diffuse Large B-Cell Lymphoma, Grade 3B Follicular Lymphoma, or Transformed Lymphoma (AFT-08)
Authors: Peter Martin, Nancy L. Bartlett, Julio C. Chavez, John L. Reagan, Sonali M. Smith, Ann S. LaCasce, Jeffrey A. Jones, James Drew, Chengqing Wu, Leandro Cerchietti, John P. Leonard
Journal: Blood (2018)
Overestimation of the Benefit-to-Harm Ratio of Risk-Based Mammography Screening in the United Kingdom
Authors: Philippe Autier
Journal: JAMA Oncology (2019)

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
Bone Marrow T Cell Changes By Multiplex IHC after Treatment with Flotetuzumab, a CD123 x CD3 Bispecific Dart® Protein, in a Primary Refractory t-AML Patient
Authors: John Godwin, Carmen Ballesteros-Merino, Carlo B Bifulco, Helene Lelièvre, Jon Wigginton, Jan K Davidson-Moncada, Bernard Fox
Journal: Blood (2018)
CAR T Cell Cytotoxicity Is Dependent on Death Receptor-Driven Apoptosis
Authors: Nathan Singh, Olga Shestova, Katharina Hayer, Albert Hong, Pranali Ravikumar, Atushi Hoshino, Ophir Shalem, Matthew D. Weitzman, Carl H June, Saar I. Gill, Marco Ruella
Journal: Blood (2018)
Landscape of Recurrent Mutations in Non-Coding Genome with Functional Implications in Newly-Diagnosed Multiple Myeloma
Authors: Mehmet Kemal Samur, Chandraditya Chakraborty, Raphael Szalat, Anil Aktas Samur, Mariateresa Fulciniti, Michael A Lopez, Masood A. Shammas, Paul Richardson, Florence Magrangeas, Stephane Minvielle, Philippe Moreau, Michel Attal, Anjan Thakurta, Kenneth Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Nikhil Munshi
Journal: Blood (2018)
Efficacy and safety of burosumab in children aged 1–4 years with X-linked hypophosphataemia: a multicentre, open-label, phase 2 trial
Authors: Michael P Whyte, Thomas O Carpenter, Gary S Gottesman, Meng Mao, Alison Skrinar, Javier San Martin, Erik A Imel
Journal: The Lancet Diabetes & Endocrinology (2019)
Pharmacologic Targeting of Hypoxia-Inducible Factors
Authors: Gregg L. Semenza
Journal: The Annual Review of Pharmacology and Toxicology (2019)

Hypoxia-inducible factors (HIFs) control transcriptional responses to reduced O 2 availability. HIFs are heterodimeric proteins composed of an O 2 -regulated HIF-α subunit and a constitutively expressed HIF-1β subunit. HIF-α subunits are subject to prolyl hydroxylation, which targets the proteins for degradation under normoxic conditions. Small molecule prolyl hydroxylase inhibitors, which stabilize the HIF-α subunits and increase HIF-dependent expression of erythropoietin, are in phase III clinical trials for the treatment of anemia in patients with chronic kidney disease. HIFs contribute to the pathogenesis of many cancers, particularly the clear cell type of renal cell carcinoma in which loss of function of the von Hippel-Lindau tumor suppressor blocks HIF-2α degradation. A small molecule inhibitor that binds to HIF-2α and blocks dimerization with HIF-1β is in clinical trials for the treatment of renal cell carcinoma. Targeting HIFs for stabilization or inhibition may improve outcomes in diseases that are common causes of mortality in the US population.
Oligodendrocyte Progenitor Cells Become Regionally Diverse and Heterogeneous with Age
Authors: Sonia Olivia Spitzer, Sergey Sitnikov, Yasmine Kamen, Kimberley Anne Evans, Deborah Kronenberg-Versteeg, Sabine Dietmann, Omar de Faria, Sylvia Agathou, Ragnhildur Thóra Káradóttir
Journal: Neuron (2019)

Oligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during CNS development, are the main proliferative cells in the adult brain. OPCs are conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell electrophysiological recordings, that OPCs start out as a homogeneous population but become functionally heterogeneous, varying both within and between brain regions and with age. These electrophysiological changes in OPCs correlate with the differentiation potential of OPCs; thus, they may underlie the differentiational differences in OPCs between regions and, likewise, differentiation failure with age.
Abstract 13092: Cardiac MRI Practice: An Analysis of 2012 and 2013 Medicare Provider Utilization and Payment Data
Authors: James W Goldfarb
Journal: Circulation (2015)

Introduction: The Centers for Medicare and Medicaid Services (CMS) recently released detailed information on services provided to Medicare beneficiaries by physicians for 2012 and 2013. The information provides individual provider information based on HCPCS code, number of services and payment. Additionally, demographic information is provided for each physician. We analyzed these databases to determine the number of cardiac MRI services provided, physician payment, characteristics of providers and changes over time to provide insight into the practice of cardiac MRI in the United States. Methods: The 2012 and 2013 Medicare Provider Utilization and Payment Data: Physician and other Supplier Public Use File (PUF) was downloaded and searched for cardiac MRI HCPCS codes (75557-75564). Statistics were calculated for the number of providers, number of services, payment, geographic location and type of facility. Additionally, provider degree, gender and clinical specialty were analyzed. Changes from 2012 to 2013 were statistically compared. Results: In 2012, there were 311 (84% male) providers with 11,473 cardiac MR scans. The number of MRI scans per provider (36.9±39.2; range: 11-260) varied widely. In 2013, the number of providers increased to 337 (85% male) with 12,076 cardiac MR scans (35.8±36.7; range: 11-246). Physician identified specialty was 48% Cardiology and 46% Diagnostic Radiology. Payment (2013) was less (p&lt;0.001) in facilities ($125.8±8.6; n=10,107) compared to non-facilities ($451.75±123.3; n=1,969). In Figure 1, the number of MR scans (2013) are displayed geographically and by HCPCS code. Conclusions: Cardiac MR utilization slightly increased and payment decreased from 2012 to 2013. Usage was split evenly between Cardiology and Diagnostic Radiology, but providers were predominantly male.
THU0152 Serum presepsin as a novel biomarker for bacterial infection in rheumatoid arthritis patients treated with tocilizumab
Authors: E. Oguro, S. Tsuji, K. Kuzuya, Y. Okita, H. Matsuoka, S. Teshigawara, M. Yoshimura, Y. Harada, M. Matsushita, S. Ohshima, J. Hashimoto, Y. Saeki
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tocilizumab (TCZ), an inhibitor of interleukin-6 (IL-6), has been widely used to treat rheumatic diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis. Recently, TCZ was approved for use in patients with giant cell aortitis and Takayasu aortitis. However, TCZ treatment sometimes obscures changes in the conventional biomarkers for infection such as serum levels of C-reactive protein (CRP) and procalcitonin (PCT). Presepsin (P-SEP), a subtype of soluble CD14, has been recently identified as a biomarker for sepsis. In addition, we have reported the usefulness of P-SEP for the diagnosis of bacterial infection in RA patients because it is less affected by the disease activity. <h3>Objectives</h3> To examine the usefulness of P-SEP in RA patients complicated with bacterial infections during TCZ treatment. <h3>Methods</h3> In this study, 49 RA patients with bacterial infections (i+RA), 76 RA patients without bacterial infections (RA) and 23 healthy controls (HC) were enrolled. The presence of infection was strictly diagnosed by bacteriological examinations, typical clinical characteristics such as fever (38.0°C) and/or CRP elevation and/or increased white blood cell count, and improvements of these manifestations with antibiotics. Serum P-SEP levels were measured by an immunoassay. The CRP and PCT levels were measured simultaneously. <h3>Results</h3> The median serum P-SEP levels were 186.0 [interquartile range (IQR), 134.0–236.0], 691.0 [IQR, 345.5–842.0], 154.5 [IQR, 145.8–165.5] l, and 161.0 [IQR, 146.5–166.0] pg/mL for TCZ (n=25), i+TCZ (pre-antibacterial treatment; n=7), i+TCZ (post-antibacterial treatment; n=7) and the HC group, respectively. The P-SEP levels of the i+TCZ group were significantly elevated compared with those of the TCZ group (p&lt;0.001). The i+TCZ group displayed elevated P-SEP levels despite normal CRP and PCT levels. After antibacterial treatment, P-SEP levels of the i+TCZ group were significantly decreased (p=0.016). <h3>Conclusions</h3> These results suggest that serum P-SEP levels are less affected by TCZ treatment compared with other conventional inflammatory biomarkers such as CRP and PCT. Moreover, P-SEP levels are useful for the assessment of bacterial infections in RA patients treated with TCZ. <h3>Reference</h3> [1] Tsuji S, et al. Mod Rheumatol2017;27(4):718–720. <h3>Disclosure of Interest</h3> None declared