tbuckley/cabot-search huggingface dataset:
FRI0209 Recommendations for acquisition and considerations for interpretation of mri of the spine and sacroiliac joints in the investigation of axial spondyloarthritis in the uk
Authors: T. Bray, A. Jones, M.A. Hall-Craggs, A. Bennett, P.G. Conaghan, A. Grainger, R. Hodgson, C. Hutchinson, M. Leandro, P. Mandl, D. McGonagle, P. O’Connor, R. Sengupta, M. Thomas, A. Toms, N. Winn, H. Marzo-Ortega, P.M. Machado
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The use of magnetic resonance imaging (MRI) has been instrumental in the early recognition and characterisation of axial spondyloarthritis (axSpA). However, a recent survey in the UK showed that there is diverse practice in the use of MRI and limited knowledge of MRI features suggestive of axSpA among radiologists.<sup><sup>1</sup></sup> <h3>Objectives</h3> To develop clinical practice recommendations for the acquisition and interpretation of MRI of the spine and sacroiliac joints (SIJs) in the investigation of axSpA through a collaboration between rheumatologists and radiologists. <h3>Methods</h3> A working group comprising 9 rheumatologists and 9 musculoskeletal radiologists with an interest in axSpA was established. The EULAR standardised operating procedures were followed.<sup><sup>2</sup></sup> Two working group meetings were held, the first to define the scope of the exercise and the second to review the results of the Systematic Literature Review that informed the recommendations. An anonymised Delphi process was used to formulate the final set of recommendations. The level of evidence and strength of recommendation was added to the recommendations. The level of agreement by working group members was assessed using a numerical rating scale. <h3>Results</h3> A total of 2 overarching principles and 7 recommendations were formulated (figure 1). The first 3 recommendations address the MRI acquisition protocol, namely anatomical areas to be scanned and sequences to be used. The remaining 4 recommendations address the interpretation of active and structural lesions of the spine and SIJs. <h3>Conclusions</h3> A UK joint rheumatology and radiology consensus on the most appropriate MRI acquisition protocol and interpretation of images in the investigation of axSpA was achieved. This consensus will help standardise practices and ensure prompt and effective patient management in the diagnosis and treatment of axSpA. <h3>References</h3> [1] Bennett, et al. J Rheumatol2017. [2] van der Heijde, et al. Ann Rheum Dis2015. <h3>Acknowledgements</h3> This work was financially supported by the British Society for Spondyloarthritis (BRITSpA). <h3>Disclosure of Interest</h3> None declared
THU0021 Differential effects of tr14 versus diclofenac on cox/lox pathways revealed by rnaseq
Authors: G. St. Laurent, I. Toma, B. Seilheimer, M. Tackett, J. Zhou, M. Ri, D. Shtokalo, Y. Vyatkin, T. Jepson, K. Cesnulevicius, T. Mccaffrey
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-inflammatory agents are used widely in treating numerous pain and inflammatory conditions. With a focus on the COX/LOX pathways in cutaneous wound repair in mice, the therapeutic activities of Tr14 (Traumeel), a multicomponent/multitarget natural product, and diclofenac (NSAID), a non-selective cyclooxygenase (COX) inhibitor were compared. The COX enzymes convert arachidonic acid into prostaglandins and thromboxanes, while the lipoxygenase (LOX) pathway generates more pro-inflammatory leukotrienes. Differential effects were identified via transcriptome analysis (RNAseq). <h3>Objectives</h3> To compare the transcriptomic changes after administration of Tr14 or diclofenac in a mouse cutaneous wound healing model, with particular emphasis on the COX/LOX pathway. <h3>Methods</h3> After abrasive wounding, the wounds were treated with topical Tr14 (34 mg/ml) in combination with subcutaneous Tr14 injections (9.5 mg/ml), or with subcutaneous Tr14 injections only, or topical diclofenac at clinically relevant doses (2 mg/ml). Skin samples were analysed for RNA transcript profiling by RNAseq at specific times (12 hour, 24 hour, 36 hour, 72 hour, 96 hour, 120 hour, 192 hour) after injury. Differentially expressed genes (DEGs) were computed at each time point between diclofenac vs control or Tr14 vs control, using EdgeR. <h3>Results</h3> At early time points (12–36 hour), both control and Tr14-treated wounds showed marked increase in the inducible COX2 enzyme mRNA, while diclofenac-treated wounds did not, likely due to blocking the PGE2 necessary for the feedback induction. Tr14, in contrast, had a striking inhibitory effect on mRNA levels for leukotriene A4 hydrolase, which converts LTA4 to LTB4; microsomal glutathione S-transferase, which converts LTA4 to LTC4; and gamma-glutamyltransferase (LTC4 &gt;LTD4). In contrast, Tr14, but not diclofenac strongly induced Nrf2 mRNA at 12–36 hours. <h3>Conclusions</h3> Tr14 and diclofenac had very different effects on the COX/LOX synthetic pathway after cutaneous wounding. Tr14 allowed normal autoinduction of COX2 mRNA by PGE2, but suppressed mRNA levels for the key enzymes in the leukotriene synthetic pathway. A likely explanation for these effects is that Tr14 strongly induced Nrf2 mRNA, which is known to co-repress the leukotriene enzymes via transcription factor Bach1. <h3>Disclosure of Interest</h3> None declared
Use of Statins, Survival and Incidence of Thrombosis Among Older Adults with Polycythemia Vera: A Population-Based Study
Authors: Nikolai Podoltsev, Mengxin Zhu, Rong Wang, Amer M. Zeidan, Xiaoyi Wang, Amy J. Davidoff, Scott F Huntington, Smith Giri, Steven D. Gore, Xiaomei Ma
Journal: Blood (2018)
LCL161, an Oral Smac Mimetic/IAP Antagonist for Patients with Myelofibrosis (MF): Novel Translational Findings Among Long-Term Responders in a Phase 2 Clinical Trial
Authors: Naveen Pemmaraju, Bing Z Carter, Hagop M. Kantarjian, Jorge E. Cortes, Tapan M. Kadia, Guillermo Garcia-Manero, Courtney D. DiNardo, Prithviraj Bose, Naval G. Daver, Marina Y. Konopleva, Maro N. Ohanian, Sherry A. Pierce, Lingsha Zhou, Zeev E. Estrov, Gautam Borthakur, Karina Salinas, Po Yee Mak, Nitin Jain, Elias J. Jabbour, Srdan Verstovsek
Journal: Blood (2018)
Abstract 18150: Prediction of Imminent Deterioration of Children after Stage I Palliation Using Real-Time Processing of Physiological Data
Authors: Craig G Rusin, Sebastian I Acosta, Eric L Vu, Risa B Myers, Kenneth M Brady, Daniel J Penny
Journal: Circulation (2014)

Patients after stage 1 palliation (S1P) for hypoplastic left heart syndrome (HLHS) and related lesions are at risk of life threatening deterioration resulting in shock, cardiac arrest, &amp; hypoxemia. We hypothesize that these sudden deteriorations may be forecast by subtle, previously unidentified changes in cardiorespiratory dynamics. Identification of these precursors may provide an opportunity for early, life-saving intervention. We created complete high-resolution physiological recordings for all patients who had a primary admission of S1P after Jan. 1, 2013. We used the SickbayTM system (Medical Informatics Corp, Houston, TX) to collect high frequency physiological waveforms including EKG, ABP, LAP, SpO2 and Chest Impedance (60Hz - 240Hz), as well as HR, RR, Temp. and ST segment vital signs (0.5 Hz) during the patient’s interstage hospitalization. A logistic regression model was constructed to discriminate between physiological characteristics observed in the hours prior to deterioration from the characteristics observed &gt;24 hours prior to or &gt;96 hours after a clinical deterioration. Model validation was done using a standard bagging approach with a REPtree classifier and 10 fold cross validation. Twenty five patients were included in the study. Of these, 15 (60%) were found to have one or more deterioration events (arrest, CPR, unplanned intubation), with 24 total events observed during the interstage period. Characteristics associated with imminent deterioration were low SpO2 and depressed ST segment. Changes in physiological dynamics could be detected 1-2 hours before overt deterioration occurs (ROC area = 0.89) (Figure 1). This altered physiological state remains for ~96 hours after deterioration. In conclusion, it is possible to identify clinical deterioration in HLHS patients during their interstage period ~1-2 hours before overt deterioration occurs, providing an opportunity for early, life-saving intervention to be administered.
SAT0636 Repeatability of mri diffusion weighted imagingof sacroiliac joints in patients with axial spondyloarthritis and healthy subjects
Authors: J.M. Møller, M. Østergaard, H.S. Thomsen, I.J. Sørensen, O.R. Madsen, S.J. Pedersen
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Bone marrow oedema (BME) localised in sacroiliac joints (SIJ) as assessed by Short Tau Inversion Recovery (STIR) or T2 weighted fat saturated (T2w FS) sequences is one of the two cornerstones in the classification criterion for axial spondyloarthritis (SpA). Since Diffusion Weighted Imaging (DWI) can quantify water diffusion by measuring the Apparent Diffusion Coefficient (ADC), DWI may potentially be an alternative or supplementary imaging method to STIR or T2w FS.<sup>1</sup> <h3>Objectives</h3> The purpose was to measure the repeatability of (ADC) in a standardised Region-of-Interest (ROI) setting in healthy subjects and in active and chronic SpA patients and to compare the subjects. <h3>Methods</h3> SpA patients and sex- and age- matched healthy subjects were examined twice within 7±2 days in the same MRI unit. Short Tau Inversion Recovery (STIR), T1 weighted and DWI sequences were performed in the semi-coronal plane. ADC map was calculated on basis of 4 b values: 0; 50; 500; 800. On each consecutive slice in the cartilaginous compartment the SIJ was divided into four quadrants. From the joint surface a 5 mm deep ROI was drawn. In all ROIs median and 95th percentile ADC values were measured. Intraclass Correlation Coefficients (ICC) were measured to assess repeatability, and unpaired T tests to compare subgroups. Actives were defined as BME on STIR and non-actives as no BME on STIR. <h3>Results</h3> 25 SpA patients and 24 healthy subjects were enrolled. For all subjects inter-reader ICC was 0.66 and intra-reader ICC 0.92 for the median ADC and 0.57 and 0.74 for the 95th percentile ADC. In SpA patients, healthy subjects, females, males, actives and non-actives Inter-reader ICC was 0.79, 0.27, 0.42, 0.72, 0.78 and 0.52 for the median ADC and 0.74; 0.73, 0.68, 0.60, 0.88, 0.64, and 0.64 for the 95th percentile. Intrareader ICC was excellent for median ADC and good to excellent for 95th percentile ADC (table 1). Significant differences in median (figure 1A) and 95th percentile (fig 1B) ADC were measured between females versus males (p=0.03; p=0.02) and actives versus non-actives (p=0.01; p=0.01) but not in patients versus healthy controls. <h3>Conclusions</h3> ADC seems a reliable parameter in SpA patients but not in healthy subjects. Our data encourage further studies of ADC measurements for discrimination of SpA patients with or without active inflammation. <h3>Reference</h3> [1] Navallas M, et al. Radiographics2013;33(4):933–956. <h3>Disclosure of Interest</h3> None declared
Minimal Residual Disease Detection at RNA and Leukemic Stem Cell (LSC) Level. Comparison of Qpcr, d-PCR and CD26 Stem Cell Measurements in Chronic Myeloid Leukemia (CML) Patients in Deep Molecular Response (DMR)
Authors: Elisabetta Abruzzese, Monica Bocchia, Simona Bernardi, Malgorzata Monika Trawinska, Donatella Raspadori, Camilla Zanaglio, Francesco Bondanini, Anna Sicuranza, Paola Pacelli, Michele Malagola, Paolo de Fabritiis
Journal: Blood (2018)
AB0776 Muscle ultrasonography: a potential new diagnostic tool for inflammatory myopathies
Authors: K. Bhansing, C. Saris, J. Fransen, F. van den Hoogen, A. Verrips, R. Cooper, P. van Riel, B. van Engelen, S. Pillen, M. Vonk
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Quantitative muscle ultrasound (QMUS) imaging has proven to be a useful, non-invasive technique to visualise normal and pathological skeletal muscle tissue.<sup>1</sup> Electromyography (EMG) findings are not always disease specific in patients suspected of idopathic inflammatory myopathies (IIM). <h3>Objectives</h3> To assess diagnostic value of QMUS in patients suspected for an IIM and to compare results with EMG. <h3>Methods</h3> In 57 patients, suspected for IIM, panel diagnosis blinded for QMUS was used as reference standard. QMUS results were used to classify patients according an ultrasound neuromuscular disorder (NMD) algorithm (normal/borderline/abnormal). The predictive value of QMUS and EMG was assessed in a two by two table and a multivariate logistic regression model. <h3>Results</h3> Twenty-two patients (39%) were diagnosed with IIM; 8 polymyositis, 4 dermatomyositis, 4 necrotizing myopathy, 3 inclusion body myositis and 3 non-specific myositis. Sixteen patients were classified with other NMD. We found an increased echointensity of the sternocleidomastoid, biceps, forearm flexor and tibialis anterior in the IIM group. Sensitivity, specificity, positive and negative predictive values (PPV/NPV) were 82%, 51%, 51%, 82% for ultrasound NMD algorithm and 63%, 64%, 50%, 75% for EMG. Multivariate analyses showed area under the curve (AUC) (0.81) (0.69–0.92) for ultrasound NMD algorithm, EMG (0.79) (0.67–0.92) and ultrasound NMD algorithm plus EMG (0.82) (0.70–0.93). <h3>Conclusions</h3> QMUS with NMD algorithm provides a fair diagnostic value for patients suspected for an IIM and is similar to EMG results. A sizeable NPV indicates a low rate of false negative QMUS results. In addition to the relevant PPV for the presence for NMD, QMUS could serve as a potential screening tool for clinicians to detect possible myopathies and to rule out the presence of IIM. <h3>References</h3> [1] Zaidman CM, van Alfen N. Ultrasound in the Assessment of Myopathic Disorders. J Clin Neurophysiol. 2016;33(2):103–1 <h3>Disclosure of Interest</h3> None declared
Abstract O.46: A Phase I/IIa Dose Escalating, Open-label Study of Atorvastatin in Children with Acute Kawasaki Disease and Coronary Artery Abnormalities
Authors: Adriana H Tremoulet, Pei-Ni Jone, Samuel Dominguez, Marsha Anderson, Heather Heizer, Mary Glode, Jane C Burns
Journal: Circulation (2015)

Background: Although high-dose intravenous immunoglobulin plus aspirin reduces the risk of coronary artery damage, 5-10% of children with Kawasaki disease (KD) will go on to develop coronary artery aneurysms that may result in myocardial ischemia, infarction, or death. Arterial damage in KD results from immune activation and vessel wall infiltration by myofibroblasts, neutrophils, and T-cells with secretion of pro-inflammatory cytokines, elastases, and matrix metalloproteinases. Resolution of inflammation and recovery from the acute illness occurs through T-cell regulation. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, have extensive anti-inflammatory effects that target all of these pathways. These effects are independent of their cholesterol-lowering effect. Given these anti-inflammatory effects, statins would be a reasonable therapy to block coronary artery abnormality (CAA) progression in KD Methods: We designed a Phase I/IIa, two-center, dose-escalating, 6-week open-label study of atorvastatin. Acute KD patients within the first 20 days after fever onset are eligible if they are between the ages of 2 and 17 years old, have had fever for ≥ 3 days, and have ≥ 2 clinical criteria with LAD/RCA z-score ≥ 2.5 or a coronary artery aneurysm (≥ 1.5 x the adjacent segment). Dose escalation (0.125-0.75 mg/kg/day) follows a 3+3 design with evaluations for dose limiting toxicities at 2 and 6 weeks after enrollment. The primary outcome measure is safety with secondary outcome measures including the pharmacokinetics (PK) of atorvastatin, changes in measures of oxidative stress and inflammation, enumeration and characterization of regulatory T-cells, and echocardiographic changes in the internal diameter of the coronary arteries. Results: To date we have enrolled 9 subjects, 7 at Rady Children’s Hospital San Diego and 2 at Children’s Hospital Colorado. The median age at enrollment was 4 years with 5/9 (55%) males and a median illness day at enrollment of 6 days. The median baseline Z worst score was 3.5. The study is currently enrolling at the second dose level. Conclusions: The safety, tolerability, and PK of atorvastatin for acute KD patients will be established by this clinical trial.
OP0256 Hydroxychloroquine reduces risk of incident diabetes mellitus in primary sjÖgren syndrome patients: a propensity score matched population-based cohort study
Authors: W.-S. Chen, C.-Y. Tsai, C.-C. chang
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> HCQ is an antimalarial drug that is widely prescribed for the treatment of Sjögren syndrome. Glucocorticoids may alter glucose metabolism and contribute to diabetes mellitus. Treatment for primary Sjögren syndrome (SS) sometimes requires glucocorticoids that may worsen glucose homoeostasis. HCQ can reduce diabetes risk in SLE and RA. <h3>Objectives</h3> This study aimed to investigate the association of HCQ use and diabetes mellitus risk in primary SS patients. <h3>Methods</h3> This nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. In the period 2002–13, 7311 newly diagnosed primary SS patients were identified after excluding those with a previous diagnosis of RA, SLE or diabetes mellitus. The propensity score matched 4874 patients with at least 6 month hydroxychloroquine exposure after diagnosis and 2437 patients without. Incidence of diabetes mellitus was identified as a new diagnostic code using a diabetes mellitus-specific medication. <h3>Results</h3> Four hundred and ninety-seven newly diagnosed diabetes mellitus patients were identified among primary SS patients (4874 had taken HCQ and 2437 had never taken HCQ), with an average follow-up period of 4.9 years. Compared with patients without HCQ treatment, the hazard ratio (HR) of diabetes mellitus in patients taking HCQ at a cumulative dose ≥175 g was reduced [HR 0.60 (95% CI: 0.45 to 0.80), p&lt;0.001]. Higher prednisolone-equivalent dose (≥88 defined daily dose) was associated with increased risk of developing diabetes mellitus [HR 1.50 (95% CI: 1.11 to 2.03), p=0.001], which was reduced by concomitant HCQ use at a cumulative dose ≥374 g [HR 0.34 (95% CI: 0.22 to 0.56), p=0.001]. <h3>Conclusions</h3> This propensity score matched analysis of Taiwanese patients with primary SS found that use of HCQ is associated with reduced risk of incident diabetes mellitus in a dose-dependent manner. High-dose glucocorticoids increase the risk of diabetes, which can be decreased by concomitant HCQ use. <h3>Disclosure of Interest</h3> None declared
Components and Trends in Door to Treatment Times for Endovascular Therapy in Get With The Guidelines-Stroke Hospitals
Authors: Bijoy K. Menon, Haolin Xu, Margueritte Cox, Jeffrey L. Saver, Mayank Goyal, Eric Peterson, Ying Xian, Roland Matsuoka, Reza Jehan, Dileep Yavagal, Rishi Gupta, Brijesh Mehta, Deepak L. Bhatt, Gregg C. Fonarow, Lee H. Schwamm, Eric E. Smith
Journal: Circulation (2019)

Background: Endovascular therapy (EVT) is standard of care in patients with acute disabling ischemic stroke attributable to large-vessel occlusion and is more effective when delivered quickly. It is currently unclear whether time targets achieved in clinical trials can be achieved in clinical practice. We describe interval times from patient arrival in the emergency department (door) to first pass (treatment initiation) in patients receiving EVT within Get With The Guidelines-Stroke hospitals and analyze patient- and hospital-level variables associated with these times. Methods: Data are from sites participating fully as Comprehensive Stroke Centers within Get With The Guidelines-Stroke hospitals from October 2014 to September 2016. Workflow times analyzed include door to imaging, imaging to arterial access, arterial access to first pass, and the composite door to first pass time. Data are described overall and by calendar-year quarters. Multivariable modeling was used to identify patient- and hospital-level variables associated with workflow times. Results: Among 2929 patients with EVT from 195 hospitals (median age, 71 years [interquartile range {IQR}, 60–81]; 50.7% female; median baseline National Institute of Health Stroke Score, 17 [IQR, 12–22]; median annual EVT administration number, 16 [IQR, 10–27]), median door to first pass time was 130 minutes (IQR, 101–170 minutes), door to imaging time was 12 minutes (IQR, 7–20 minutes), imaging to arterial puncture time was 93 minutes (IQR, 68–126 minutes), and arterial puncture to first pass time was 18 minutes (IQR, 4–31 minutes). Overall, 3% patients achieved a door to first pass time ≤60 minutes. A statistically significant linear time trend was noted for door to first pass time (quarter 4 year 2014 median time, 134.5 minutes to quarter 3 year 2016 median time, 128 minutes, P =0.002). In multivariable analysis, older age, arrival during nonregular hours, and history of diabetes mellitus were associated with longer door to first pass time. Hospitals achieving shorter door to intravenous alteplase administration (door to needle) times were more likely to achieve faster door to first pass time ( P &lt;0.001). Each 5 cases/y increase in EVT case volume was associated with a 3% shorter door to first pass time, up to a case volume of 40 per year ( P &lt;0.001). Conclusions: Although EVT treatment times are modestly improving, additional efforts are needed to streamline workflow so that the true potential of this treatment is realized. These data may inform benchmark goals for EVT workflow times.
Allotransplants for Patients 65 Years or Older with High-Risk Acute Myeloid Leukemia
Authors: Paul Lin, Lauren Westfall Veltri, Katy Rezvani, Betul Oran, Sairah Ahmed, Gheath Alatrash, Rohtesh S. Mehta, Gabriela Rondon, Partow Kebriaei, Uday Popat, Yago Nieto, Chitra Hosing, Roy B Jones, Muzaffar H. Qazilbash, Issa F. Khouri, Elizabeth J. Shpall, Richard E Champlin, David Marin
Journal: Blood (2018)