tbuckley/cabot-search huggingface dataset:
THU0054 Utility of serological parameters in giant cell arteritis for predicting disease complications
Authors: K Lakota, J Feichtinger, B Burja, T Kuret, P Žigon, Ž Rotar, R Ješe, S Sodin-Šemrl, S Čučnik, G Thallinger, M Tomšič, A Hočevar
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Giant Cell Arteritis (GCA) is a systemic vasculitis affecting primarily large and medium sized arteries. Immediate high dose steroid treatment may prevent urgent complications, such as vision loss and cerebrovascular insults<sup>1–3</sup>. However, there is a clear lack of data on predicting serological markers and their association to clinical complications. <h3>Objectives</h3> To investigate serological parameters that support clinicians in predicting complications in a large, clinically well-characterized set of untreated GCA patients at time of diagnosis. <h3>Methods</h3> The study included 98 GCA patients (67% female) with a median (IQR) age 74.1 (67.3–78.8) years and a median (IQR) symptome duration time of 30 (20–90) days). Healthy blood donors (HDs, n=52, 61.5% female, median (IQR) age of 41.95 (20.4–63.1) years) served as controls. GCA complications studied were visual disturbances (including permanent loss of vision), relapses, peripheral artery involvement and claudication. Levels of 27 serum analytes were measured using Luminex xMAP Technology. Interleukin-6 (IL-6) and serum amyloid A (SAA) levels were tested using ELISA and nephelometry, respectively. <h3>Results</h3> The highest, significantly elevated analytes in GCA vs. HDs were SAA (85-fold &gt; HDs mean values), IL-23 (63-fold) and IL-6 (11-fold). IL-13, α-fetoprotein and MMP-2 were significantly decreased in GCA, while levels of IL-2, IL-17A and TNF-α were unchanged. PCA analysis revealed a signature analyte profile positioning towards the HD cluster. SAA, CRP, haptoglobin, ESR, thrombocyte # and matrix metalloproteinase-1 (MMP-1) all negatively associated with visual disturbances, confirming our previous data. Age showed significant association to permanent visual loss, with older patients being more affected<sup>3</sup>. SAA, CRP and ESR at presentation were found to be predictive of relapsing disease, while MMP-2 negatively associated with relapse. VCAM-1, α-fetoprotein, MARCO and IL-27 were all negatively associated with peripheral artery involvement. MMP-2 and MARCO showed positive association with claudication, while IL-18 was negatively associated. <h3>Conclusions</h3> In our large study of untreated GCA patients we highlight the importance of using serological acute phase parameters, MMPs and other analytes for predicting complications. <h3>References</h3> Weyand CM, Goronzy JJ. Medium- and large-vessel vasculitis. N Engl J Med 2003, 349:160–169. Nesher G: The diagnosis and classification of giant cell arteritis. J Autoimmun 2014, 48–49:73–75. Hocevar A et al. Do Early Diagnosis and Glucocorticoid Treatment Decrease the Risk of Permanent Visual Loss and Early Relapses in Giant Cell Arteritis: A Prospective Longitudinal Study. Medicine (Baltimore) 2016, 95:e3210. <h3>Disclosure of Interest</h3> None declared
AB0907 Contribution of imaging in the diagnosis of infectious spondylodiscitis
Authors: H Sahli, A Bachali, R Tekaya, I Mahmoud, O Saidane, L Abdelmoula
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Infectious spondylodiscitisis represents a diagnostic and therapeutic emergency. Imaging is fundamental in the management of the disease. <h3>Objectives</h3> The aim of this study is to analyze the contribution of imaging in the diagnosis of infectious spondylodiscitis. <h3>Methods</h3> This is a retrospective study which included medical records of patients treated for psoas abcess during the twelve past years [2006–2016]. Epidemiologic, clinical, and imaging data (Standard X ray, Computed tomography (CT), magnetic resonance imaging (MRI)) were recorded and analysed. <h3>Results</h3> Ninety patients were included in this study. The average age was 55 years [16–86] with an even distribution between males and females. Mean symptom duration was of 4 months. The most frequently isolated pathogen was Mycobacterium tuberculosis (63.3%), followed by pyogenic germs (21.2%) and Brucella (15.5%). Standard X ray were pathological in 89% of cases: showed narrowing of intervertebral space (72.2%), endplate destruction (42.2%), erosions of vertebra (13.3%), opacity (12.2%), vertebral fracture (10%), paravertebral spindle (5.5%) and posterior archlysis lesion (2.2%). Standard radiographswere normal in 12 cases and in 1 case, spinal CT showed vertebral destruction wirh " mirror-image ". Spinal MRI, performed in the remaining 11 cases, confirmed the diagnosis in all cases and showed paravertebral collections (n=3), epiduritis (n=3), psoas abscess (n=2), microabscess (n=1) and spinal compression (n=1). In case of posterior archlysis lesion and vertebral fracture, MRI confirmed the diagnosis by showing paravertebral collections. <h3>Conclusions</h3> Management of infectious spondylodiscitis has benefited from advancements in imaging allowing an early diagnosis and treatment. <h3>Disclosure of Interest</h3> None declared
TMEM16A/ANO1 Inhibits Apoptosis Via Downregulation of Bim Expression
Authors: Neal R. Godse, Nayel Khan, Zachary A. Yochum, Roberto Gomez-Casal, Carolyn Kemp, Daniel J. Shiwarski, Raja S. Seethala, Scott Kulich, Mukund Seshadri, Timothy F. Burns, Umamaheswar Duvvuri
Journal: Clinical Cancer Research (2017)

Abstract Purpose: TMEM16A is a calcium-activated chloride channel that is amplified in a variety of cancers, including 30% of head and neck squamous cell carcinomas (HNSCCs), raising the possibility of an anti-apoptotic role in malignant cells. This study investigated this using a multimodal, translational investigation. Experimental Design: Combination of (i) in vitro HNSCC cell culture experiments assessing cell viability, apoptotic activation, and protein expression (ii) in vivo studies assessing similar outcomes, and (iii) molecular and staining analysis of human HNSCC samples. Results: TMEM16A expression was found to correlate with greater tumor size, increased Erk 1/2 activity, less Bim expression, and less apoptotic activity overall in human HNSCC. These findings were corroborated in subsequent in vitro and in vivo studies and expanded to include a cisplatin-resistant phenotype with TMEM16A overexpression. A cohort of 41 patients with laryngeal cancer demonstrated that cases that recurred after chemoradiation failure were associated with a greater TMEM16A overexpression rate than HNSCC that did not recur. Conclusions: Ultimately, this study implicates TMEM16A as a contributor to tumor progression by limiting apoptosis and as a potential biomarker of more aggressive disease. Clin Cancer Res; 23(23); 7324–32. ©2017 AACR.
FRI0413 Acute effect of iloprost on peripheral circulation as assessed by videocapillaroscopy and 22-mhz power doppler ultrasonography
Authors: T Schioppo, A Orenti, P Boracchi, O De Lucia, A Murgo, PL Meroni, F Ingegnoli
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Vascular involvement is a hallmark of systemic sclerosis (SSc) and it is responsible for some of the most common complications of the disease such as Raynaud9s phenomenon (Rp), digital ulcers (DUs) and pulmonary arterial hypertension. I.V. iloprost (ILO), a prostacyclin analogue, has been shown to be effective in reducing Rp severity, DUs healing and preventing [1]. <h3>Objectives</h3> To assess the acute effect of ILO on acral circulation as assessed by nailfold videocapillaroscopy (NVC) and 22-MHz Power Doppler ultrasound (PDUS). <h3>Methods</h3> 44 SSc consecutive patients fulfilling the 2013 EULAR classification criteria were enrolled. Each patient was evaluated before and immediately after I.V. ILO administration (0.5–2.0 ng/Kg/min for 6 consecutive hours). PDUS was performed at the 3rd and 4th finger of the dominant hand after exclusion of ulnar artery occlusion (UAO). In case of UAO non-dominant hand was examined. Ultrasound investigation was performed with Esaote MyLab 70 XVG by means of linear array transducer (10–22 MHz). Power Doppler settings were standardized (Doppler frequency 14.3 MHz, Gain 55%, PRF 750 Hz). PDUS measurements included sagittal scan of nailbed and fingertip qualitatively graded from 1 (no signal) to 4 (marked hyperemia) [2], and resistivity index (RI) of ulnar and radial proper digital arteries. Capillary width (sum of capillary width/mm) was calculated by NVC with magnification 200X performed on two images of the same digits examined by PDUS. <h3>Results</h3> The study population included 44 SSc patients, 40 (90.9%) women, 35 (79.5%) limited cutaneous SSc, median age 60.2 years old and median disease duration 8 years. 19 (43.2%) had history of DUs, among them 15 had experienced more than one DUs and 1 had active DU at the moment of evaluation. Semiquantitative perfusion score of sagittal scan of nailbed and fingertip pre- and post-therapy are shown in Table 1. Changes in RI and capillary width pre- and post-infusion are reported in Table 2. <h3>Conclusions</h3> A statistically significant post-infusion rise in RI, fingertip and nailbed PDUS grade were found. Capillary width was also increased, but it was not statistically significant. As such, these novel results indicate that ILO, alongside its clinical effect, is able to enhance vascularization even at the most peripheral levels. <h3>References</h3> Pope J et al. Cochrane Database Syst Rev. 2000;(2):CD000953. Newman JS et al. Radiology. 1996,198:582–584. <h3>Disclosure of Interest</h3> None declared
AB0202 Low dose acetylsalicylic acid as primary prophylaxis of cardiovascular events in rheumatoid arthritis. a longitudinal, retrospective study
Authors: D Iacono, S Fasano, V D'Abrosca, I Pantano, R Chieffo, G Valentini
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Cardiovascular events (CV) i.e. acute myocardial infarction and stroke are recognized as a leading cause of mortality in patients with Rheumatoid Arthritis (RA) [1,2]. Acetylsalicylic acid (ASA) is known to be associated with a significant decrease in the incidence of CV events in patients at high risk for atherosclerosis like patients with diabetes [3] and has been recently reported to play a primary prophylactic role of CV events in Systemic Lupus Erythematosus by our team [4]. <h3>Objectives</h3> To investigate the so far unexplored role of ASA in reducing CV morbidity in RA. <h3>Methods</h3> We analysed patients admitted to our Outpatient clinic from January to December 2015. Out of 199, 155 patients, who had been followed from January 2000 and had not experienced any CV event at the first visit, were enrolled. The incidence of CV morbidity was recorded at December 2016. <h3>Results</h3> The 155 patients had been followed-up for a median of 8 years (range 1–15 years). Out of them, 111 patients had been treated with ASA, that we currently administer to patients undergoing steroid treatment. During the 15-years of follow up, 5 CV events (2 cerebrovascular, 3 acute myocardial infarction) had occurred (Incidence rate 3.93/1000 person/year). Interestingly, only 1 CV event had occurred in ASA treated patients (Incidence rate 1.12/1000 person/year) with respect to 4 in the non-ASA group (44 patients) (Incidence rate 10.48/1000 person/year) (p=0.0146). <h3>Conclusions</h3> Our study has several limitations including the low number of patients and CV events. Nevertheless, it might suggest a primary prophylactic role of ASA in RA, that awaits to be investigated in large controlled prospective studies. <h3>References</h3> Arthritis Rheum. 2001 Dec;44(12):2737–45. High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditionalcardiac risk factors. del Rincόn ID, Williams K, Stern MP, Freeman GL, Escalante A. BMC Musculoskelet Disord. 2014 Apr 29;15:142. Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature. Meek IL, Vonkeman HE, van de Laar MA. Diabetes Res Clin Pract. 2016 Oct;120:31–9. Aspirin for primary prevention of cardiovascular disease in patients with diabetes: A meta-analysis. Kokoska LA, Wilhelm SM, Garwood CL, Berlie HD. Rheumatology (Oxford). 2016 Sep;55(9):1623–30. Low-dose aspirin as primary prophylaxis for cardiovascular events in systemic lupus erythematosus: a long-term retrospective cohort study. Iudici M, Fasano S, Gabriele Falcone L, Pantano I, La Montagna G, Migliaresi S, Valentini G. <h3>Disclosure of Interest</h3> None declared
AB0414 The use of rituximab in patients with rheumatoid arthritis: in which infusion intervals were given and how did they respond? HUR-BIO real life results
Authors: B Armagan, A Sari, A Erden, L Kilic, O Karadag, A Akdogan, S Apras Bilgen, U Kalyoncu, I Ertenli, S Kiraz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Rituximab is one of the treatment options in rheumatoid arthritis (RA) patients and officially recommended as a maintanance treatment given every 6 months after the initial loading of first course. <h3>Objectives</h3> In this real life study, it was aimed to investigate the infusion frequency of rituximab maintanance treatment and possible effects on disease activity. <h3>Methods</h3> The HUR-BIO is a single-center biologic registry of Hacettepe University which is established in Ankara and in which patients have been prospectively recorded since 2012. This database has 1235 RA patient records as of August 2016. Rituximab was prescribed at least once in 273 (22.1%) patients. The residence address of 85 those patients was within the boundaries of center city (Ankara) and they were included in to the study. In our clinic, the dates and the DAS-28 scores at the time of rituximab courses were recorded. Rituximab infusion compliance was classified as; “regular ” if there is less than one month delay, “slightly irregular” if less than 3 months delay and “irregular” if more than 3 months delay. <h3>Results</h3> The mean age of the 85 patients (80% female) was 59.1 (10.1), the mean disease duration was 12.9 (8.6) years and 74.1% of patients were seropositive. 39/85 (46%) patients previously used at least one biological agent (46 (54%) patients were biologic naive before Rituximab therapy). Median rituximab course number was 3 (1–8). A total of 211 rituximab courses were given to 85 patients. Rituximab course number and percentage is shown in figure. The mean interval time between rituximab courses was 7.9 (2.8) months. Total of 102 (52.6%) courses were admistred at normal times regularly, 60 (30.9%) were slightly irregular and 32 (16.5%) were irregular. There was no significant difference between the mean DAS-28 responses in the time of the courses and the rituximab infusion compliances [in regular group mean DAS-28 was 3.31 (1,19), in slightly irregular group mean DAS-28 was 3.26 (1.35) and irregular group mean DAS-28 was 3,57 (1.34), p&gt;0.05]. Before rituximab courses, 33.7% of patients had remission, 19.1% had low disease activity, 36.3% had moderate disease activity and 10.9% had high disease activity. <h3>Conclusions</h3> Rituximab administration was approximately 2 months delayed in RA patients who were living in center-city boundaries. The pre-treatment mean disease activity scores were similar, even if there was a delay in rituximab administration. In our center, about 85% of patients were taking RTX courses regular and/or slightly irregular and about half of the patients before treatment were in remission and/or low disease activity. <h3>Disclosure of Interest</h3> None declared
FRI0162 Antibody response to 13-valent pneumococcal conjugate vaccine is not impaired in patients with rheumatoid arthritis (RA) or sjogrens syndrome without dmard treatment compared to controls
Authors: P Nived, J Nagel, T Saxne, P Geborek, T Mandl, L Skattum, MC Kapetanovic
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To investigate if antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) is impaired in patients with rheumatoid arthritis (RA) and primary Sjogrens syndrome (pSS) without treatment, with methotrexate (MTX) or hydroxychloroquine (HCQ), compared to healthy controls. <h3>Methods</h3> In total, 61 patients with RA (51 without DMARD and 10 on MTX), 23 patients with pSS (18 without DMARD and 5 on HCQ) and 49 controls were vaccinated with a single dose (0.5 ml) PCV13 intramuscularly. Pre- and postvaccination serotype-specific antibody concentrations for pneumococcal serotypes 6B and 23F and functionality of antibodies (23F) were determined in serum samples taken immediately before and 4–6 weeks after vaccination using ELISA and opsonophagocytic activity (OPA) assay, respectively. Proportions of individuals with positive antibody response (i.e. ≥2-fold increase from prevaccination concentrations) for both serotypes were calculated and groups were compared using Chi2 test. Percentage change (pre- to postvaccination) in OPA was calculated and groups were compared using Mann-Whitney U test. <h3>Results</h3> Pre- to postvaccination antibody concentrations (Table) increased significantly for both serotypes and in both patient and control groups (<i>p</i>&lt;0.001). Antibody response to serotypes 6B and 23F was decreased in patients with RA on MTX treatment (both <i>p</i>&lt;0.01), but not in RA without DMARD or pSS with or without HCQ, compared to controls (Figure). Proportions of antibody responders to both serotypes did not differ significantly between groups RA without DMARD (51%), pSS (48%) and controls (55%). After vaccination, OPA increased in groups RA without DMARD (<i>p</i>&lt;0.001), pSS without DMARD (<i>p</i>=0.01) and controls (<i>p</i>&lt;0.001), but did not change significantly in patients with RA on MTX and pSS on HCQ. The mean percentage change in OPA was lower in RA on MTX (1.8%, <i>p</i>=0.01), RA without DMARD (8.9%, <i>p</i>&lt;0.01) and pSS on HCQ (-1.5%, <i>p</i>=0.01), but not in pSS without DMARD (11.0%), compared to controls (17.9%). <h3>Conclusions</h3> Pneumococcal conjugate vaccine is immunogenic in patients with RA and pSS without DMARD treatment. Both antibody response and functionality of antibodies is impaired in patients with RA on MTX. <h3>Disclosure of Interest</h3> None declared
Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and <i>F508del</i>/<i>F508del-CFTR</i> or <i>F508del</i>/<i>G551D-CFTR</i>
Authors: Scott H. Donaldson, Joseph M. Pilewski, Matthias Griese, Jon Cooke, Lakshmi Viswanathan, Elizabeth Tullis, Jane C. Davies, Julie A. Lekstrom-Himes, Linda T. Wang
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor.Objectives: To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D.Methods: This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day).Measurements and Main Results: Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV1 (ppFEV1) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all).Conclusions: These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis.Clinical trial registered with www.clinicaltrials.gov (NCT01531673).
Ibrutinib for chronic graft-versus-host disease after failure of prior therapy
Authors: David Miklos, Corey S. Cutler, Mukta Arora, Edmund K. Waller, Madan Jagasia, Iskra Pusic, Mary E. Flowers, Aaron C. Logan, Ryotaro Nakamura, Bruce R. Blazar, Yunfeng Li, Stephen Chang, Indu Lal, Jason Dubovsky, Danelle F. James, Lori Styles, Samantha Jaglowski
Journal: Blood (2017)
THU0147 Thorax ct findings in a large cohort of patients with rheumatoid arthritis: hur-bio real life results
Authors: A Sari, B Armagan, A Erden, L Kilic, O Karadag, A Akdogan, S Apras Bilgen, I Ertenli, U Kalyoncu, S Kiraz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Lungs are one of the target organs in rheumatoid arthritis (RA) patients. Interstitial lung disease (ILD), rheumatoid nodules, pleural effusion, bronchiectasia and small airway disease are common manifestations of lung involvement. <h3>Objectives</h3> Objective of this study was to evaluate distribution of Thorax CT findings and treatment features in RA patients registered in a biologic registry. <h3>Methods</h3> HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a prospective, single center database of biological treatments including 1229 RA patients by August 2016. Demographics, clinical and serological features of patients and thorax CT results performed in Hacettepe University between 2000 and 2016 were retrospectively evaluated. Patients whose CT was reported as small airway disease or ILD by radiologists, were evaluated as a subgroup. Data included type of biological treatments before diagnose of ILD and at last control as well. <h3>Results</h3> Among 1229 patients (78.8% female), mean age was 53.3±12.9 and disease duration was 11.4±7.9. Thorax CT had been performed in 203 (16.5%) patients. Distribution of pathologic findings in thorax CT was represented in Table 1. 29 patients (%2.4) were diagnosed as ILD with regard to CT findings. Patients with ILD were older (64.5±6.7 vs 60.6±10.1, p=0.039) and more frequently positive for rheumatoid factor (RF) (25/27 (%92.6) vs 77/121 (%63.3), p=0.003) than patients without ILD. ILD was detected before beginning of biologics in 11 (37.9%) patients and during biologic treatment in 18 (62.1%) patients. Honeycombing was seen in 10 (34.5%) patients. First choice of biologic agent was RTX in 10 (34.5%) and TNFi in 19 (65.5%) patients. In ILD patients, mean follow-up duration was 51±31 months and first biologic was switched to another in 16 (55.2%) of patients. At the last follow-up visit 19 (65.5%) patients were on rituximab, 3 (10.3%) patients were on abatacept and 7 (24.1%) were on TNFi. Small airway disease was detected in 19 (9.3%) patients. History of smoking was present in only 4 (21.0%) of patients with small airway disease. <h3>Conclusions</h3> Bronciectasia, rheumatoid nodules, small airway disease and ILD were the most frequent CT findings of RA patients. Rituximab was the choice of first biologic treatment in one third of patients, however two-thirds of patients were on rituximab therapy at the last follow-up visit. Lung involvement stands out as an important factor in selection of biologics. <h3>Disclosure of Interest</h3> None declared