tbuckley/cabot-search huggingface dataset:
Low-pass Whole-genome Sequencing of Circulating Cell-free DNA Demonstrates Dynamic Changes in Genomic Copy Number in a Squamous Lung Cancer Clinical Cohort
Authors: Xiaoji Chen, Ching-Wei Chang, Jill M. Spoerke, Kathryn E. Yoh, Vidushi Kapoor, Charles Baudo, Junko Aimi, Mamie Yu, May M.Y. Liang-Chu, Rebecca Suttmann, Ling-Yuh Huw, Steven Gendreau, Craig Cummings, Mark R. Lackner
Journal: Clinical Cancer Research (2019)

Abstract Purpose: We developed a method to monitor copy number variations (CNV) in plasma cell-free DNA (cfDNA) from patients with metastatic squamous non–small cell lung cancer (NSCLC). We aimed to explore the association between tumor-derived cfDNA and clinical outcomes, and sought CNVs that may suggest potential resistance mechanisms. Experimental Design: Sensitivity and specificity of low-pass whole-genome sequencing (LP-WGS) were first determined using cell line DNA and cfDNA. LP-WGS was performed on baseline and longitudinal cfDNA of 152 patients with squamous NSCLC treated with chemotherapy, or in combination with pictilisib, a pan-PI3K inhibitor. cfDNA tumor fraction and detected CNVs were analyzed in association with clinical outcomes. Results: LP-WGS successfully detected CNVs in cfDNA with tumor fraction ≥10%, which represented approximately 30% of the first-line NSCLC patients in this study. The most frequent CNVs were gains in chromosome 3q, which harbors the PIK3CA and SOX2 oncogenes. The CNV landscape in cfDNA with a high tumor fraction generally matched that of corresponding tumor tissue. Tumor fraction in cfDNA was dynamic during treatment, and increases in tumor fraction and corresponding CNVs could be detected before radiographic progression in 7 of 12 patients. Recurrent CNVs, such as MYC amplification, were enriched in cfDNA from posttreatment samples compared with the baseline, suggesting a potential resistance mechanism to pictilisib. Conclusions: LP-WGS offers an unbiased and high-throughput way to investigate CNVs and tumor fraction in cfDNA of patients with cancer. It may also be valuable for monitoring treatment response, detecting disease progression early, and identifying emergent clones associated with therapeutic resistance.
Abstract 13238: Artificial Intelligence Improve Personalized Risk Prediction in High Risk Heart Failure Patients Post Cardiac Transplant
Authors: Bashar Al hemyari, Jinsung Yoon, William Zame, Mihaela Van Der Schaar, Martin Cadeiras
Journal: Circulation (2018)

Background: Careful selection of heart transplant candidates is vital to optimize organ utilization and maximize post-transplant survival especially in highly heterogenic cohorts with underrepresen...
Biallelic TET2 Inactivation in Myeloid Neoplasia: From Clonal Hierarchy to Clinical Phenotypes
Authors: Hassan Awada, Yasunobu Nagata, Abhinav Goyal, Mohammad Fahad B. Asad, Bhumika J. Patel, Cassandra M. Hirsch, Teodora Kuzmanovic, Vera Adema, Mai Aly, Bartlomiej P. Przychodzen, Yihong Guan, Wenyi Shen, Louis Williams, Aziz Nazha, Mohamed Abazeed, Mikkael A. Sekeres, Tomas Radivoyevitch, Torsten Haferlach, Babal K. Jha, Valeria Visconte, Jaroslaw P. Maciejewski
Journal: Blood (2018)
V(D)J Sequence Capture for DNA-Based Minimal Residual Disease Detection in Multiple Myeloma
Authors: Even H Rustad, Malin Hultcrantz, Venkata D Yellapantula, Theresia Akhlaghi, Caleb Ho, Maria E Arcila, Mikhail Roshal, Akshar Patel, Sean M Devlin, Austin Jacobsen, Ying Huang, Jeffrey E Miller, Elli Papaemmanuil, Ola Landgren
Journal: Blood (2018)
SAT0117 High uric acid as a risk factor for cardiovascular diseases in rheumatoid arthritis patients
Authors: A. Al-Herz, A. Aldei, K. Saleh, A. Al-Awadhi, W. Al-Kandari, E. Hasan, A. Ghanem, M. Hussain, E. Nahar, F. Abutiban, A. Alenizi, Y. Ali, H. Alhajeri, S. Hayat, A. Khadrawy, A. Fazal, K. Mokaddem, A. Zaman, G. Mazloum, Y. Bartella, S. Hamed, R. Alsouk, A. Al-Saber
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular diseases (CVD). It is unclear whether an elevated serum uric acid (UA) further increases that risk. <h3>Objectives</h3> We study CVD and their risk factors in association with UA in RA patients. <h3>Methods</h3> Adult patients who satisfied the ACR classification criteria for RA from The Kuwait Registry for Rheumatic Diseases (KRRD) from four major hospitals were evaluated from February 2013 through May 2017. Patients with recorded UA were identified and CVD and their risk factors were studied in those patients. To optimize classifier number and prediction accuracy, hierarchical cluster analyses for multiple factors were performed, which indicated nine possible independent CVD risk factors. A binary logistic regression was conducted to examine their significant association with CVD and the independence of UA as a risk factor. <h3>Results</h3> A total of 564 RA patients with available UA were identified, 353(62.6%) females. Mean age was 50.8±11.5 years and disease duration 10.5±2.9 years. Mean UA was 271±78 µmol/L. Of those patients, 31 (5.5%) were reported to have CVD. UA was significantly correlated to the presence of CVD (χ<sup>2</sup>=6.49, <i>p</i>=0.011). Logistic regression model indicated a 10% increase of CVD with every 10 µmol/L increase in UA. A correlation matrix between UA and other risk factors showed a significant association between high uric acid and a younger age at RA diagnosis (r=-0.262), hyperlipidemia (r=0.191) and diabetes mellitus (r=0.244). <h3>Conclusions</h3> Our study suggests that UA may be an independent risk factor for CVD and is associated with the presence of other risk factors. UA should be measured and carefully approached in RA patients. <h3>Disclosure of Interest:</h3> None declared
Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Peter A LeWitt, Robert A Hauser, Rajesh Pahwa, Stuart H Isaacson, Hubert H Fernandez, Mark Lew, Marie Saint-Hilaire, Emmanuelle Pourcher, Lydia Lopez-Manzanares, Cheryl Waters, Monika Rudzínska, Alexander Sedkov, Richard Batycky, Charles Oh
Journal: The Lancet Neurology (2019)
The Imperative for Climate Action to Protect Health
Authors: Andy Haines, Kristie Ebi
Journal: New England Journal of Medicine (2019)

limate change is already adversely affecting human health and health systems, 1,2 and projected climate change is expected to alter the geographic range and burden of a variety of climate-sensitive health outcomes and to affect the functioning of public health and health care systems.If no additional actions are taken, then over the coming decades, substantial increases in morbidity and mortality are expected in association with a range of health outcomes, including heat-related illnesses, illnesses caused by poor air quality, undernutrition from reduced food quality and security, and selected vectorborne diseases in some locations; at the same time, worker productivity is expected to decrease, particularly at low latitudes. 3,4Vulnerable populations and regions will be differentially affected, with expected increases in poverty and inequities as a consequence of climate change.Investments in and policies to promote proactive and effective adaptation and reductions in greenhouse-gas emissions (mitigation) would decrease the magnitude and pattern of health risks, particularly in the medium-to-long term.
THU0447 No advantage of methotrexate in the treatment of giant cell arteritis
Authors: I. Monjo Henry, Luis Coronel, Ignacio Castaño, Diana Peiteado, Sara García-Carazo, Alejandro Balsa, Eugenio de Miguel
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The high-dose glucocorticoids (GCs) are the mainstay of treatment in Giant Cell Arteritis (GCA). Patients treated with greater GCs dosages are at the greatest risk of morbidity. Immunosuppressive agents have been trialled in an effort to reduce toxicity from GCs and to improve efficacy of treatment. The results of one meta-analysis with the three trials that included methotrexate (MTX) showed a weak benefit in those patients receiving MTX, but the results were heterogeneous, with one trial showing significant benefit, while the other two did not.<sup>1</sup> <h3>Objectives</h3> To study the efficacy and safety of MTX adjunct to GCs in the treatment of GCA. <h3>Methods</h3> New-onset giant-cell arteritis initiating treatment of the disease was included in a retrospective observational study to compare treatment efficacy and safety. According to the treatment received the patients were divided two groups: GCs alone (group 1) and MTX and GCs (group 2). To avoid bias, we defined a subgroup of patients in which only patients who started MTX in the first trimester of treatment were included (group 3). As efficacy outcome the number of relapses and the cumulative dose of GCs at 6, 12 and 24 months were collected. For safety, the number of emergency room visits, hospitalisation admissions and infections were investigated in the follow-up. <h3>Results</h3> One hundred twenty- three patients were included, 74 (60.2%) women, the mean age was 79,41 years old. Fifty-six (45.53%) received GCs alone (group 1) and 67 (54.48%) received GCs and MTX as an adjuvant treatment at some time during follow- up (group 2). 30 of these 83 patients (24.39% of total patients) received MTX in the first trimester after diagnosis (group 3). The cumulative doses of GCs, number of patients with relapses, visits to the emergency room and hospitalisation admissions are shown in the table 1. In none of these variables there were statistically significant differences among the three groups, except for the number of patients with relapses, which was greater in group 2 than in group 1 (p=0.03). The number of relapses in patients who received MTX early (group 3) was 56.7%, in the rest of patients (who only received GCs and those who started MTX after the first trimester) was 52.69%–33.3% of the patients in group 3% and 21.5% of the rest of the patients presented infections. <h3>Conclusions</h3> Whilst MTX have been used in an effort to reduce toxicity from GCs and to improve efficacy of treatment our observational study shows that there is no benefit from adjunct MTX in GCA either in terms of efficacy or toxicity. <h3>Reference</h3> [1] Mahr AD, Jover JA, Spiera RF, et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data metaanalysis. Arthritis Rheum2007;56(8):2789–2797. <h3>Disclosure of Interest</h3> None declared
Garden of Endurance
Authors: Jack Coulehan
Journal: JAMA (2019)

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First Results of a Prospective I/II Clinical Trial in Adult Patients Using TCR Alpha/Beta Depleted Stem Cell Transplantation from Matched Related and Unrelated Donors
Authors: Moniek De Witte, Anna Van Rhenen, Geerte Van Sluis, Rick Admiraal, Lotte van der Wagen, Eefke J. Petersen, Reinier Raymakers, Monique C Minnema, Anke Janssen, Kasper Westinga, Constantijn J.M. Halkes, J.H. Frederik Falkenburg, Jaap Jan Boelens, Jurgen Kuball
Journal: Blood (2018)
THU0474 Utilisation of anti-osteoporotic drugs in real-world data: an analysis of persistence to therapy and risk of fracture
Authors: V. Orlando, V.M. Monetti, F. Guerriero, A. Moretti, V. Russo, A. Piscitelli, G. Iolascon, E. Menditto
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoporosis is a chronic progressive disease characterised by low bone mass and deterioration of bone structure, leading to an increate risk of fractures. It is a major public health problem, affecting hundreds of millions of people worldwide. The primary aim of pharmaceutical therapy is to reduce the risk of osteoporotic fractures. However, long-term adherence to therapy is requie for optimal therapeutic benefit for patients with osteoporosis. Poor adherence is considered to be one primary reason for suboptimal clinical benefit. <h3>Objectives</h3> The aim of this study was to investigate the determinants of non-persistence and impact of persistence on the risk of fractures by using administrative databases. <h3>Methods</h3> We conducted a retrospective cohort study using administrative data from four local health authorities in the Abruzzo Region (Central Italy), which comprise about 9 00 000 inhabitants (68% of the overall regional population). The final cohort consisted of a total of 7862 patients, aged ≥60 years, identified through records of filled prescriptions for an antiosteoporotic drug between January 1, 2006 to December 31, 2006. The primary outcome of this study was persistence at one year. Persistence was defined as the length of time (in days) from the date of the index prescription to the date of discontinuation therapy. <h3>Results</h3> Kaplan – Meier analysis showed that 3733 patients (47.5%) were persistent with antiosteoporotic drugs after 1 year. An adjusted analysis showed that there is a big difference in persistence between women and men: women are more likely to be non-persistent than men (HR:1.94). Switcher patients were more likely to be non-persistent (HR:1.22). The odds of fracture were significantly higher for patients with previous fractures in comparison with those without previous fractures [OR, 1.70, (95% CI, 1.12–2.59)] (table 1) <b>Table 1</b> Logistic regression model: impact of persistence and other factors on the risk fracture <h3>Conclusions</h3> Persistence with antiosteoporotic drugs is a significant predictor of incurring a fracture. For these reason, improving osteoporosis treatment compliance and persistence represents one of a major challenge for the future. <h3>References</h3> [1] Casula M, Filippi A, Flacco E, Gambera M, Manzoli L, Menditto E, Orlando V, Piccinelli R, Tragni E, Catapano A. Assessment and potential determinats of compliance and persistence to anti-osteoporosis therapy in Italy. Am J Manag Care2014;20(5):e138-e145. [2] Iolascon G, Gimigliano F, Orlando V, Capaldo A, Di Somma C, Menditto E. Osteoporosis drugs in real-world clinical practice: an analysis of persistence. Aging Clin Exp Res2013Oct;25 Suppl 1:S137–41. <h3>Disclosure of Interest</h3> None declared
Clinical Outcome Associated with Cytomegalovirus (CMV) Infection/Disease in CMV-Seropositive Adult Patients after Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Regis Peffault De Latour, Patrice Chevallier, Didier Blaise, Aurore Clement, Thierry Allavoine, Abir Tadmouri, Josefin Blomkvist, Alain Duhamel, Ibrahim Yakoub-Agha
Journal: Blood (2018)
FRI0442 Long-term treatment with rituximab in interstitial lung disease related to systemic sclerosis: our clinical experience
Authors: F. Lumetti, A. Spinella, A. Ariani, E. Cocchiara, M. Colaci, M. Silva, N. Sverzellati, C. Ferri, C. Salvarani, D. Giuggioli
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Systemic sclerosis (SSc) is an immune-mediated disorder characterised by abnormal fibrosis and diffuse microangiopathy with skin and internal organ involvement. Interstitial lung disease (ILD) represents one of the most challenging complication of SSc, difficult to manage and correlate with a poor prognosis. Chest Computed Tomography (CT) is the gold standard for detection and evaluation of SSc-ILD by means of semi-quantitative scoring of extent of lung involvement. Some preliminary data suggest that rituximab (RTX) may be usefully employed in the treatment of SSc patients. <h3>Objectives</h3> To investigate the role and effect of RTX on ILD in our SSc patients' series. <h3>Methods</h3> We retrospectively evaluated a series of 18 SSc patients (M/F 6/12, mean age 54.6±17.6 SD years, mean disease duration 11.4±6.5 SD years, L/D cutaneous subsets 6/12) who received one or more cycles of RTX (4 weekly infusions of 375 mg/m2) every 6 months for a total of 1–6 cycles. Lung involvement was studied by means of pulmonary function tests (PFTs) (18/18) and inspiratory chest CT (10/18) before and after treatment. In particular, we considered PFTs performed 6 months before RTX, at time 0, one year after the first RTX cycle, and at the end of follow-up (13.7±7.3 years). ILD extent score was assessed by the semi-quantitative method proposed by Goh et al (2008).<sup>1</sup> <h3>Results</h3> Forced vital capacity (FVC%) significantly reduced during the year before RTX treatment [from 95.2±17.4 to 84.8±16.4; p=0.0017], as well as the diffusing capacity for carbon monoxide (DLCO%) [from 58.1±14.3 to 47.6±12.9; p=0.0002]. Conversely, FVC% and DLCO% stabilised one year after the first RTX cycle (80.8±23 and 47.8±15.7, respectively), and at the end of the follow-up (84.3±24.6 and 54.8.8±12.3, respectively; p=0.0001). In our cohort, only 7/10 patients had ILD detectable on CT before treatment. At the end of the follow-up we observed that ILD extented in 6/7 cases one patient remained stable, the three subjects without ILD did not developed pulmonary fibrosis. <h3>Conclusions</h3> According to PFTs results, our study showed that RTX could stabilise the progression of lung function tests in SSc patients. However, the semi-quantitative visual score identified radiological pulmonary worsening in many patient with stabilised PFTs. Therefore, the correlations between functional and radiological outcomes are so weak that many Authors suggested they should be considered together in SSc-ILD assessment. <h3>Reference</h3> [1] Goh NSL, Desai SR, Veeraraghavan S, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med2008;177:1248–54. <h3>Disclosure of Interest</h3> None declared
Judge throws out AbbVie’s case against NHS England’s hepatitis C programme
Authors: Nigel Hawkes
Journal: BMJ (2019)

NHS England has defeated a legal challenge by AbbVie against its £1bn (€1.1bn; $1.3bn) procurement of drugs to eliminate hepatitis C, enabling the programme to go ahead.

AbbVie claimed in the Technology and Construction Court that the procurement procedure had failed to treat all bidders fairly. But in a judgement given on 18 January by Mr Justice Choudhury, these arguments were rejected.1

The court action delayed the start of the programme by six months. NHS England said at the time the action was launched that AbbVie’s claims were “embarrassing for lack of particulars.”

The procurement was designed to achieve an affordable price for the drugs so that NHS England could plan to eliminate hepatitis C, believed to affect around 160 000 people, by 2025. Appealing to the industry to …
OP0104 Antibodies against carbamylated proteins are involved in osteoclastogenesis by inducing rankl expression in osteoblasts in vitro
Authors: F.R. Spinelli, R. Mancini, M. Leopizzi, T. Colasanti, A. Pecani, F. Ceccarelli, F. Conti, G. Valesini, C. Alessandri
Journal: Annals of the Rheumatic Diseases (2018)

Burning bones <h3>Background</h3> Citrullinated peptide are one of the main target of immune response in Rheumatoid Arthritis (RA) and antibodies to citrullinated peptides (ACPA) are involved in bone resorption. One of the target antigens – citrullinated vimentin – is expressed on the surface of osteoclast precursors where it can bind the antibodies starting the differentiation in mature osteoclast. Moreover, recent data demonstrated that serum levels of receptor activator of nuclear factor-κB ligand (RANKL) are higher in ACPA-positive RA patients. RANKL is the main osteoblast-derived cytokine inducing osteoclastogenesis. Antibodies directed against carbamylated proteins (Anti-CarP) have been recently described in RA patients with Rheumatoid Arthritis. The effect of anti-CarP on bone resorption has not been yet addressed. <h3>Objectives</h3> The aim of the study was to investigate <i>in vitro</i> the effect of anti-CarP on Osteoprotegerin (OPG) and RANK ligand (RANKL) production in osteoblast cultures. <h3>Methods</h3> Anti-CarP were investigated by ELISA in the sera of 88 RA patients using carbamylated fetal calf serum (CarFCS) and non-modified FCS as antigens. Anti-CarFCS were purified from the sera of 3 RA patients who tested highly positive for anti-CarP. Osteoblasts were isolated from the femoral head of 3 patients undergoing total hip arthroplasty and cultured in three different conditions – 1 ng/ml of anti-CarFCS, 10 ng/ml of anti-CarFCS or control medium for 4–6 days, until confluence. RNA was extracted from cell lysates and OPG and RANKL mRNA expression was analysed by Real-time PCR. Moreover, OPG and RANK expression was investigated by immunofluorescence on treated and non-treated cells. differences were determined either with two-way repeated measures analysis of variance (ANOVA) with Bonferroni's multiple comparison test, using Prism 5.0 software. A p value&lt;0.05 was considered significant. <h3>Results</h3> In osteoblast cultures, anti-CarFCS decreased the expression of OPG and increased the expression of RANKL in a dose-dependent manner, leading to an increase in RANKL/OPG ratio (figure 1A and 1B). The result was confirmed by the immunofluorescence analysis demonstrating the subcellular co-location of OPG and RANKL in osteoblast cultures (figure 1C). <h3>Conclusions</h3> The results of the study confirm that anti-CarFCS can be detected in nearly 40% of RA patients. The increase of RANKL/OPG ratio in the osteoblast cultures treated with anti-CarFCS suggests an effect of such autoantibodies on osteoclastogenesis and osteoclasts activity, supporting their possible involvement in the development of bone erosions. <h3>Disclosure of Interest</h3> None declared