tbuckley/cabot-search huggingface dataset:
FRI0353 Serum proteomics profile in systemic sclerosis patients
Authors: M De Santis, E Generali, A Ceribelli, N Isailovic, M Caprioli, GM Guidelli, C Selmi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic sclerosis (SSc) is characterized in virtually all patients by anti-nuclear antibodies (ANA) with anti-centromere (ACA), anti-topoisomerase I (ant-Scl70), and anti-RNA polymerase III antibodies identifying patient subgroups. However, there are no reliable biomarkers predicting SSc susceptibility and internal organ involvement. <h3>Objectives</h3> We aimed to identify serum protein biomarkers associated with SSc and interstitial lung disease (ILD), using a highly multiplexed proteomic technology. <h3>Methods</h3> We analyzed serum samples of 3 patients with SSc and ILD (2 limited SSc: one ANA positive and one anti-Scl70 positive, and one diffuse SSc anti-Scl70 positive), 3 patients with SSc and no ILD (ACA positive limited SSc), and 4 healthy controls. All subjects were women and age matched. Serum proteomics profiling was performed using the SOMAscan platform (SomaLogic, Inc., Boulder, CO, USA). Statistical analysis included Student9s t-test and were performed using the SomaSuite software (SomaLogic, Boulder, CO, USA). <h3>Results</h3> Proteomic analysis identified 33 proteins which differentiate SSc from HC and 9 proteins which differentiate SSc patients with and without ILD. Compared to healthy controls, SSc cases showed an altered expression of proteins involved in extracellular matrix formation and cell-cell adhesion, angiogenesis, and lymphocyte recruitment, activation, and signaling, while an overall inhibition of neutrophil function was noted. An interferon and IL-1 signatures were also found. Patients with SSc and ILD manifested increased protein levels related to intracellular signaling and cell cycle, along with an increase of monocyte chemoattractants and ligands for the leukocyte adhesion compared to SSc without ILD. We further observed a decrease in B cell stimulating factor and IL-22 signaling in SSc with ILD. <h3>Conclusions</h3> Serum proteomic profiles can differentiate SSc from healthy controls and SSc patients with and without ILD; moreover, our results identify biomarkers with a putative pathogenetic significance. <h3>Disclosure of Interest</h3> None declared
AB0463 Therapeutic plasma exchange (TPE) for refractory SLE: a comparison of outcomes between different sub-phenotypes?
Authors: A Soyuoz, O Karadag, L Kilic, T Karaagac Akyol, S Apras Bilgen, OI Ozcebe
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Therapeutic plasma exchange (TPE) offers an alternative therapeutic modality for patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). However, there is conflicting evidence regarding its efficacy in different sub-phenotypes. <h3>Objectives</h3> This study aims to investigate the main clinical characteristics and outcomes of patients with different phenotypes of SLE and APS treated with TPE at a tertiary care centre. <h3>Methods</h3> Database of Blood and Apheresis Unit between 2001–2013 was screened for patients with SLE and primary APS. SLE disease activity index (SELENA-SLEDAI), the indications for treatment, complications and outcomes were obtained from review of medical records and phone calls. A total of 24 patients (SLE: 20, APS: 4) were recruited for the study. <h3>Results</h3> Mean ages of SLE (M/F: 1/19) and primary APS (PAPS) patients (M/F: 2/2) were 32.4±12.89 and 52.0±10.7, respectively. The main indications for TPE were haematologic, neurologic, pulmonary involvement and APS-related. TPE was preferred in 8 patients because of leukopenia, and co-infection. SLEDAI was significantly decreased after TPE (16.7±8.3 vs. 8.8±3.1, p=0.001). Both primary APS and SLE related CAPS patients had completely responded to TPE. Success rate of TPE in patients with thrombocytopenia were lower than patients with haemolytic anaemia. Median (IQR 25%&gt;75%) TPE sessions were 6.5 (5–10.5). <h3>Conclusions</h3> This study suggests catastrophic antiphospholipid syndrome (CAPS) and other APS related problems respond well to the TPE treatment. TPE should be kept in mind for the treatment of patients with other features of SLE, especially those resistant to other agents and in the presence of leukopenia and psychosis <h3>Disclosure of Interest</h3> None declared
Cost savings of conversion from filgrastim or pegfilgrastim to biosimilar filgrastim-sndz for chemotherapy-induced (febrile) neutropenia (CIN/FN) prophylaxis and expanded access to biosimilar GCSF on a budget neutral basis.
Authors: Ali McBride, Ivo Abraham, Karen MacDonald, Kim Campbell, Mohan Bikkina, Sanjeev Balu
Journal: Journal of Clinical Oncology (2017)

e18334 Background: Biosimilar filgrastim (Zarxio) provides a more cost-efficient alternative to reference and pegylated filgrastim for CIN/FN prophylaxis. Using biosimilar conversion rates, we determined savings achieved, number needed to convert (NNC) to purchase additional Zarxio, and the incremental number (n) of patients (pts) that could be provided Zarxio on a budget neutral basis using various filgrastim cycle/treatments scenarios. Prior real-world practice studies have shown variations in GCSF duration including shorter durations (Weycker 2006; Gascon 2016) relative to registration trials and guideline recommendations. Methods: Calculations were done for a panel of 20000 pts; chemotherapy of 1 or 6 cycles with 5, 7 or 11 filgrastim injections; cost of medicines using average selling price (Zarxio $245.08, Neupogen $283.87, Neulasta $3761.22) and subcutaneous administration per Current Procedural Terminology ($42.31 hospital outpt). NNC is the n to be converted to Zarxio to purchase 1 additional Zarxio dose or the full regimen. This yielded the incremental n that could receive any of the 6 prophylaxis scenarios budget neutrally. Results: See table below. Conclusions: A 20000 pt panel yields expanded access to Zarxio, on a budget-neutral basis, to 2699 additional pts if 100% are converted from Neupogen; and to 4063 to 32939 additional pts, depending on cycles/treatments, if converted from Neulasta. Weycker et al, Ann Pharmacother 2006;40:402-7. Gascon et al, Support Care Cancer 2016;24:911-25. [Table: see text]
Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy
Authors: Ethan J. Rowin, Anais Hausvater, Mark S. Link, Patrick Abt, William Gionfriddo, Wendy Wang, Hassan Rastegar, N. A. Mark Estes, Martin S. Maron, Barry J. Maron
Journal: Circulation (2017)

Atrial fibrillation (AF), the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), is capable of producing symptoms that impact quality of life and is associated with risk for embolic stroke. However, the influence of AF on clinical course and outcome in HCM remains incompletely resolved.Records of 1558 consecutive patients followed at the Tufts Medical Center Hypertrophic Cardiomyopathy Institute for 4.8±3.4 years (from 2004 to 2014) were accessed.Of the 1558 patients with HCM, 304 (20%) had episodes of AF, of which 226 (74%) were confined to symptomatic paroxysmal AF (average, 5±5; range, 1 to >20), whereas 78 (26%) developed permanent AF, preceded by 7±6 paroxysmal AF episodes. At last evaluation, 277 patients (91%) are alive at 62±13 years of age, including 89% in New York Heart Association class I or II. No difference was found in outcome measures for patients with AF and age- and sex-matched patients with HCM without AF. Four percent of patients with AF died of HCM-related causes (n=11), with annual mortality 0.7%; mortality directly attributable to AF (thromboembolism without prophylactic anticoagulation) was 0.1% per year (n=2 patients). Patients were treated with antiarrhythmic drugs (most commonly amiodarone [n=103] or sotalol [n=78]) and AF catheter ablation (n=49) or the Maze procedure at surgical myectomy (n=72). Freedom from AF recurrence at 1 year was 44% for ablation patients and 75% with the Maze procedure (P<0.001). Embolic events were less common with anticoagulation prophylaxis (4/233, 2%) than without (9/66, 14%) (P<0.001).Transient symptomatic episodes of AF, often responsible for impaired quality of life, are unpredictable in frequency and timing, but amenable to effective contemporary treatments, and infrequently progress to permanent AF. AF is not a major contributor to heart failure morbidity or a cause of arrhythmic sudden death; when treated, it is associated with low disease-related mortality, no different than for patients without AF. AF is an uncommon primary cause of death in HCM virtually limited to embolic stroke, supporting a low threshold for initiating anticoagulation therapy.
AB1224-HPR Could we use the lay referral system to improve the early arthritis clinic efficiency?
Authors: M Dobroiu, M Trandafir, C Ioan, D Vasile, D Predeteanu, R Ionescu, F Berghea
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The professional9s monopoly on knowledge about disease and its treatment is something gone now, in the era of internet and patient consumerism. In addition, the interest of rheumatologists (and the interest of the society, too) shifted toward early recognition of the disease and early arthritis clinics. Education is definitely one of the solutions to increase the awareness of potential patients regarding rheumatic diseases. However most of rheumatic diseases are not very frequent in the population that raise the problem of cost efficacy of the education process. Per Eliot Freidson9s view, the members of every community of whatever kind share some cultural understandings about disease, treatment, and cure. The lay community network could be considered an instrument for dissemination of proper knowledge regarding health and could help to earlier recognition of a sign of disease related to early arthritis. <h3>Objectives</h3> To identify the opportunity of using lay network for early arthritis referral. In addition, we intended to identify the most suitable vectors from this network to be used for education and dissemination of medical knowledge. <h3>Methods</h3> 48 rheumatic patients (mean age (SD): 50.8 (14,7)) consecutively admitted in one tertiary clinic have been invited to answer to a structured questionnaire. Sex ratio (M: F) was 1:2, average disease duration 7.7 (8.3) years. <h3>Results</h3> In 28.3% cases the first sign of disease was noticed not by the patient but by somebody else, for 36.7% a delay of several months to one year was declared between first sign of disease and professional examination, 71.7% use to discuss bout health problems with their lay network (often and very often), 76.1% consider them able to give pertinent advices regarding the disease they suffer from, 45,7% are ready to act as an education vector and 41,3% are ready to participate in additional education programs. They interest in such activity is not related to gender, education level or work status. <h3>Conclusions</h3> Lay network referral could be a powerful instrument to reduce the duration between onset of rheumatic symptoms and medical visit, to increase the awareness regarding rheumatic disease, to reduce the cost of health education. Health professionals should understand how to use these networks. <h3>References</h3> Freidson, Eliot. 1960. “Client Control and Medical Practice.” American Journal of Sociology 65:374–82. Barley, Stephen R., and Gideon Kunda. 2004. Gurus, Hired Guns, and Warm Bodies: Itinerant Experts in a Knowledge Economy. Princeton, NJ: Princeton University Press. <h3>Disclosure of Interest</h3> None declared
OP0271 Corticosteroid injections for greater trochanteric pain syndrome: a randomized double-blind placebo-controlled trial
Authors: MJ Nissen, L Brulhart, A Faundez, A Finckh, D Courvoisier, S Genevey
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Although small observational studies have suggested that local corticosteroid (CS) injection may be effective in the management of the greater trochanteric pain syndrome (GTPS), no prospective placebo controlled study has been carried out to establish the efficacy of this common intervention. <h3>Objectives</h3> To perform a randomized double-blind placebo controlled trial to investigate the efficacy of local CS injection in the management of GTPS. <h3>Methods</h3> The trial was conducted in the Rheumatology unit of a University teaching hospital in Geneva, Switzerland. Inclusion criteria were lateral hip pain (LHP) for greater than 1 month, a LHP score of ≥4 in the preceding week, failure of another standard treatment (physiotherapy, analgesics, etc.) and typical LHP reproduced by palpation of the greater trochanter (GT). Participants were randomised in a 1:1 ratio to: 1) injection with a combination of local anaesthetic and CS (Treatment group), or 2) injection with normal saline solution (Placebo group). The Treatment group received 4ml of 1% Lidocaine (Rapidocain®) and 1ml of Bethametasone (Diprophos®). The Placebo group received 5ml of sterile saline solution. Injections were performed under ultrasound guidance. The study9s predefined primary outcome of interest was the difference in pain intensity at 4 weeks post-injection between the 2 groups. Secondary outcomes included the number of "responders" (pain score improvement of ≥1.5) and the number of patients with low disease activity (LDA) (pain score ≤2.0). Patients were followed up for 6 months. <h3>Results</h3> A total of 46 patients were included and there were no significant differences between the 2 groups at baseline (Table 1). There were no significant differences between the 2 groups in terms of the reduction in pain at one month post-injection, with scores of -1.5 and -2.5 (<i>p</i>=0.23) in the Treatment and Placebo groups respectively. When including all measures in the first 3 weeks and using multilevel regression, there was a marginally significant improvement in pain scores in favour of the Treatment group (p=0.08) (Figure 1). There were no significant differences in terms of the percentage of responders (p=0.32), or patients with LDA (p=0.50) between the 2 groups at follow up. There were no significant differences in pain scores between groups at 3 and 6 months post-injection. <h3>Conclusions</h3> Local corticosteroid injection in the management of GTPS is only marginally effective for a few weeks. Given the lack of long-term improvement and the potential for cortisone-related side-effects, this intervention is of limited benefit. <h3>Disclosure of Interest</h3> None declared
AB0811 Hyaluronic acid intra-articular injection versus oral atorvastatin in the treatment of knee osteoarthritis
Authors: M Jokar, Z Mirfeizi, K Hashemzadeh, H Zarei
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis is a degenerative joint disorder of articular cartilage and is the most common type of arthritis in the elderly. Some studies have suggested that Hyaluronic acid<sup>1</sup> and atorvastatin<sup>2</sup> may have a role in the treatment of osteoarthritis. <h3>Objectives</h3> The purpose of the present study was to investigate and compare the potential effects of Hyaluronic acid and Atorvastatin on the symptoms of knee osteoarthritis. <h3>Methods</h3> We conducted an open, randomized, parallel study on patients with knee osteoarthritis. Eligible patients were those who met the ACR criteria of primary knee osteoarthritis, radiologically ascertained grade I or II of knee osteoarthritis on the Kellgren-Lawrence scale, had a pain score≥60 (maximum 100) and age 50–70 years. Patients are not eligible if they had secondary osteoarthritis, systemic disease like diabetes, history of inflammatory arthritis, sever knee deformity (varus or valgus &gt;50 degree), history of coagolopathy, sever cardiovascular disease, and active infections. Patients were enrolled from outpatient clinic of Imam Reza Hospital, Mashhad, Iran. We divided them randomly into two groups; Group 1 (n=35) received intra-articular Hyaluronic acid each week for three weeks, and group 2 (n=35) received oral atorvastatin 40 mg/day orally for six months. Symptoms were assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and every month up to 6 months. <h3>Results</h3> Twenty eight patients (40%) were male and 42 patients (60%) were female. There was not a significant difference between 2 groups regard to sex (P=0.626). Mean age of patients was 57.9±1.1 years. Groups mean age did not differ significantly (P=0.710). The pain and function scores were significantly decreased only in the Hyaluronic acid group in the second month (P&lt;0.001). There was not any significant improvement in any group in the next months (figure 1). <h3>Conclusions</h3> Intra articular Hyaluronic acid improved the pain and function of patients with knee osteoarthritis in the second months after injection. Atorvastatin did not have any effect on the knee osteoarthritis symptoms during 6 months. <h3>References</h3> Petrella RJ, Petrella M. A prospective, randomized, double-blind, placebo controlled study to evaluate the efficacy of intraarticular hyaluronic acid for osteoarthritis of the knee. J Rheumatol 2006; 33:951. Pathak NN, Lingaraju MC, Balaganur V, Kant V, More AS, Kumar D, Kumar D, Tandan SK. Anti-inflammatory and chondroprotective effects of atorvastatin in a cartilage explant model of osteoarthritis. Inflamm Res. 2015 Apr;64(3–4):161–9. <h3>Disclosure of Interest</h3> None declared
ALK and ROS1 Double-Rearranged Lung Squamous Cell Carcinoma Responding to Crizotinib Treatment: A Case Report
Authors: Qiong Li, Jian Wu, Li-Xu Yan, Jun-Wei Huang, Zhou Zhang, Jin-E Zhang, Xing-Lin Gao, Ze-Ru Luo, Jing Liu, Shi-Fang Yang, Yan-Hui Liu
Journal: Journal of Thoracic Oncology (2017)

Echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) and ROS1 rearrangements have been demonstrated to be driver genes in NSCLCs that can benefit from crizotinib. ALK rearrangement occurs in approximately 5% of all lung adenocarcinomas and 1.3% of lung squamous cell cancer (SqCC), whereas ROS1 rearrangement accounts for 1% to 3% of all lung adenocarcinomas and rarely, has been reported in lung SqCC.1,2
New Insights into the Genetic Basis of Monge’s Disease and Adaptation to High-Altitude
Authors: Tsering Stobdan, Ali Akbari, Priti Azad, Dan Zhou, Orit Poulsen, Otto Appenzeller, Gustavo F Gonzales, Amalio Telenti, Emily H M Wong, Shubham Saini, Ewen F Kirkness, J Craig Venter, Vineet Bafna, Gabriel G Haddad
Journal: Molecular Biology and Evolution (2017)

Human high-altitude (HA) adaptation or mal-adaptation is explored to understand the physiology, pathophysiology, and molecular mechanisms that underlie long-term exposure to hypoxia. Here, we report the results of an analysis of the largest whole-genome-sequencing of Chronic Mountain Sickness (CMS) and nonCMS individuals, identified candidate genes and functionally validated these candidates in a genetic model system (Drosophila). We used PreCIOSS algorithm that uses Haplotype Allele Frequency score to separate haplotypes carrying the favored allele from the noncarriers and accordingly, prioritize genes associated with the CMS or nonCMS phenotype. Haplotypes in eleven candidate regions, with SNPs mostly in nonexonic regions, were significantly different between CMS and nonCMS subjects. Closer examination of individual genes in these regions revealed the involvement of previously identified candidates (e.g., SENP1) and also unreported ones SGK3, COPS5, PRDM1, and IFT122 in CMS. Remarkably, in addition to genes like SENP1, SGK3, and COPS5 which are HIF-dependent, our study reveals for the first time HIF-independent gene PRDM1, indicating an involvement of wider, nonHIF pathways in HA adaptation. Finally, we observed that down-regulating orthologs of these genes in Drosophila significantly enhanced their hypoxia tolerance. Taken together, the PreCIOSS algorithm, applied on a large number of genomes, identifies the involvement of both new and previously reported genes in selection sweeps, highlighting the involvement of multiple hypoxia response systems. Since the overwhelming majority of SNPs are in nonexonic (and possibly regulatory) regions, we speculate that adaptation to HA necessitates greater genetic flexibility allowing for transcript variability in response to graded levels of hypoxia.
Breast Cancer Surgery
Authors: Edward H. Livingston, Hsiao Ching Li
Journal: JAMA (2017)

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