tbuckley/cabot-search huggingface dataset:
SAT0589 Therapeutic education in the management of fears and beliefs in patients with chronic low back pain
Authors: R Maaoui, A Khezami, I Ksibi, I Lajnef, H Rahali, R Dhahri, I Gharsallah, L Metoui, F Lajili, S Othmani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The notions of apprehension-avoidance and beliefs are among the psychosocial factors associated with the occurrence, maintenance and strengthening of the chronic painful process. Therapeutic education is increasingly described in the literature as a means to manage these factors in order to limit the transition to a chronic stage. <h3>Objectives</h3> The aim of this study is to examine the effect of therapeutic education on fears and beliefs in chronic low back pain. <h3>Methods</h3> A prospective, comparative study was conducted with two groups of 50 patients each one having chronic low back pain. Both groups had benefited from the same physical rehabilitation program. The second group concurrently attended therapeutic education sessions. Fears and beliefs of patients and their kinesiophobia were evaluated with the FABQ: Fear-Avoidance beliefs questionnaire and the TSK: Tampa scale of kinesiophobia for the evaluation of kinesiophobia index. <h3>Results</h3> The initial evaluation of apprehension-avoidance showed a high FABQ score in two groups. Management that was limited to physical rehabilitation demonstrated no effect on the apprehension-avoidance indices evaluated by the FABQ scale. However, there was a clear improvement in apprehension and avoidance in the G2 and with a statically significant difference (P=0.03). An initial and high kinesiophobic score (≥48) was noted in two groups. G1 patients showed no significant improvement in their TSK scores after the end of the program. G2 patients who benefited from a therapeutic education workshop improved their TSK scores significantly after the program completion compared to G2. <h3>Conclusions</h3> The integration of the patient into the therapeutic education workshops improved the behavior of apprehension and kinesiophobia. This further supports the usefulness of applying cognitive therapy to our patients when restructuring of preconceived ideas about movement and physical activities. <h3>References</h3> Nguyen C, Poiraudeau S, Revel M. Lombalgie chronique: facteurs de passage à la chronicité. Rev rhum.2009;76:537–42. Butron AK, Waddel G, Tilloston KM, Sumerton N. Information and advice to patients with back pain can have positive effects. A randomized controlled trial of a novel educational book in primary care. Spine. 1999;24:2481–91. Fritz JM, George SZ, Delitto A.The role of fear-avoidance beliefs in acute low back pain: relationships with current and future disability and work status.Pain. 2000;94:7–15 <h3>Disclosure of Interest</h3> None declared
THU0487 Real-life treatment with canakinumab in systemic juvenile idiopathic arthritis – first experience from the biker registry
Authors: G Horneff, F Dressler, A Thon, K Minden
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Canakinumab (CAN) had demonstrated its efficacy and safety in SJIA pts (1). <h3>Objectives</h3> To report on the experience with CAN treatment in SJIA in the clinical practice in Germany. <h3>Methods</h3> Data on patients9 and disease characteristics, disease activity and safety reports from the German BIKER registry were analysed. <h3>Results</h3> Until Dec. 2016, 37 pts exposed to CAN were identified. In 12 pts used CAN as first biologic, 25 pts were pretreated: Tocilizumab 15, Anakinra 11, Etanercept 9, Adalimumab 9. 3 patients in the pre-exposed cohort had experienced a macrophage activation syndrome. Pts9 and disease characteristics are outlined in table 1. Pts pretreated were older, had a longer disease duration and more comorbidities than naïve patients. The proportion of pts with active arthritis, active systemic features and both were comparable. Disease activity at baseline was higher in the naïve cohort suggesting some clinical benefit from pretreatment. Dosing of CAN was comparable (<i>3.9+/-0.4 vs. 3.5+/-0.7mg/kg)</i> as well as the median treatment duration (0.8vs.1year). Treatment efficacy at last follow up was better in the naïve cohort with more pts reaching a PedACR 30/50/70/90 response while JADAS- or ACR-remission rates were comparable. Treatment was discontinued by 42% in the naïve and 48% in the exposed cohort. Reasons were inefficacy (n=7;19%), intolerance (n=2;5%) and remission (n=7;19%) of the disease and other (n=2;5%). <h3>Conclusions</h3> First experience with CAN for treatment of sJIA in clinical practice is presented. A high proportion of pts gained significant improvement. JADAS remission was reached by about 50% and ACR remission by 25–57% in both biologics pre-exposed and naïve pts while few pts discontinued treatment in remission so far. Intolerance was rare. The further long term surveillance of sJIA pts exposed CAN is intended by the registry. <h3>References</h3> Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med 2012;367(25):2396–406. <h3>Acknowledgements</h3> The authors thank I.Foeldvari, M.Hufnagel, J.Kuemmerle-Deschner, F.Weller-Heinemann, M.Sailer-Hoeck, A.Hospach, G.Heubner, C.Rietschel and B-U.Keck for contributing to the Canakinumab cohort. The German Registry is supported by an unrestricted grant from Abbvie, Germany Novartis, Germany, and Roche, Germany. <h3>Disclosure of Interest</h3> G. Horneff Speakers bureau: Abbvie, Novartis, Chugai, F. Dressler Speakers bureau: Novartis, Pfizer, A. Thon: None declared, K. Minden Speakers bureau: Abbvie, Pfizer,Roche,Genzyme,Pharm-Allergan
Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression
Authors: Mi Hee Park, Hyung-Mun Yun, Chul Ju Hwang, Sang Ick Park, Sang Bae Han, Dae Youn Hwang, Do-Young Yoon, Sanghyeon Kim, Jin Tae Hong
Journal: Theranostics (2017)

Some epidemiological studies suggest an inverse correlation between cancer incidence and Alzheimer's disease (AD). In this study, we demonstrated experimental evidences for this inverse relationship. In the co-expression network analysis using the microarray data and GEO profile of gene expression omnibus data analysis, we showed that the expression of peroxiredoxin 6 (PRDX6), a tumor promoting protein was significantly increased in human squamous lung cancer, but decreased in mutant presenilin 2 (PS2) containing AD patient. We also found in animal model that mutant PS2 transgenic mice displayed a reduced incidence of spontaneous and carcinogen-induced lung tumor development compared to wildtype transgenic mice. Agreed with network and GEO profile study, we also revealed that significantly reduced expression of PRDX6 and activity of iPLA2 in these animal models. PS2 mutations increased their interaction with PRDX6, thereby increasing iPLA2 cleavage via increased γ-secretase leading to loss of PRDX6 activity. However, knockdown or inhibition of γ-secretase abolished the inhibitory effect of mutant PSs. Moreover, PS2 mutant skin fibroblasts derived from patients with AD showed diminished iPLA2 activity by the elevated γ-secretase activity. Thus, the present data suggest that PS2 mutations suppress lung tumor development by inhibiting the iPLA2 activity of PRDX6 via a γ-secretase cleavage mechanism and may explain the inverse relationship between cancer and AD incidence.
ラット坐骨神経欠損修復のためのガイドとしてのマイクロチューブを用いた生分解性多孔質ゼイン導管の設計と最適化【Powered by NICT】
Authors: Wang Guo-Wu, Yang Hui, Wu Wei-Feng, Zhang Ping, Wang Jin-Ye
Journal: Biomaterials (2017)
AB0593 Anca-associated vasculitis with both MPO-ANCA and PR3-ANCA shares characteristics of ANCA-associated vasculitis with single ANCA
Authors: SM Kim, J Kim, SW Kang, S-C Shim, S-J Yoo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are heterogeneous group of necrotizing inflammation of small vessel and the presence of the ANCA. ANCAs are defined according to the target antigens, leukocyte proteinase 3 (PR3) and myeloperoxidase (MPO). Recently, the ANCA specificity could be better for classification of ANCA-associated vasculitides than the clinical diagnosis. A few patients have both MPO- and PR3 ANCA. However, the clinical characteristics of these patients were not known in detail. <h3>Objectives</h3> To analyze organ involvement of patients with ANCA-associated vasculitis according to ANCA type focusing both MPO- and PR3-ANCA (both-ANCA) positive vasculitis <h3>Methods</h3> The medical records of the patients with positive ANCA and clinical diagnosis or the patients with positive ANCA and vasculitis diagnosis confirmed by biopsy were reviewed at two regional tertiary hospitals. The age at diagnosis, sex, and the organ involvement of kidney, lung, upper airway (nose/sinus/ear), skin, peripheral nervous system, central nervous system, and gastrointestinal tract were collected. The clinical variables were analyzed by ANCA type. <h3>Results</h3> Total 82 patients with positive ANCA and clinical diagnosis or histologic diagnosis of vasculitis were searched. MPO-ANCA positive patients was 63 (76.8%), PR3-ANCA 9 (11.0%), and both MPO- and PR3-ANCA was 10 (12.2%). The age at diagnosis of patients with PR3-ANCA was younger than patients with MPO-ANCA or both-ANCA (PR3-ANCA, 49.6 vs. MPO-ANCA, 66.1 vs. both-ANCA, 62.1, p&lt;0.05). Moreover, kidney involvement were MPO-ANCA was 77.8%, PR3-ANCA 22.2%, and both-ANCA 80% (p&lt;0.05). Upper airway involvement was also significantly associated with ANCA type (PR3-ANCA, 66.7% vs. MPO-ANCA, 23.8% vs. both-ANCA, 50.0%, p&lt;0.05). The involvement of skin, central or peripheral nervous system, gastrointestinal tract or the presence of lung fibrosis and lung nodule or mass did not differ according to ANCA type. <h3>Conclusions</h3> ANCA-associated vasculitis with both MPO-ANCA and PR3-ANCA has more kidney involvement than ANCA-associated vasculitis with PR3-ANCA and more upper airway involvement than ANCA-associated vasculitis with MPO-ANCA. <h3>Disclosure of Interest</h3> None declared
Regulation of PD-L1 in breast cancer.
Authors: Ioannis Zerdes, Nikolaos Tsesmetzis, John Lovrot, Charlotte Rolny, Jonas C. S. Bergh, Georgios Rassidakis, Theodoros Foukakis
Journal: Journal of Clinical Oncology (2017)

e23088 Background: Programmed death ligand 1 (PD-L1, CD274) is currently being investigated as a therapeutic target in breast cancer (BC), however its transcriptional regulation has not been elucidated. Methods: Three BC cells lines, one negative (MCF7) and two positive (MDA-MB-231, BT549) for PD-L1 were used. Protein expression of potential regulators of PD-L1, including Myc, STAT3, p-rpS6 (mTOR effector), Erk and p53 was assessed by western blotting and immunohistochemistry. Furthermore, transfections with small interfering RNAs (siRNAs) of selected proteins or plasmids and pharmacologic inhibition were performed. Fluorescent in situ hybridization (FISH) analysis was used for PD-L1 gene amplification studies. Publically available gene expression data derived from The Cancer Genome Atlas (TCGA) database (cBioportal) were analyzed for correlations between mRNA levels of PD-L1 and potential regulators. Results: PD-L1 gene amplification was not detected in BC cells expressing PD-L1, suggesting non-genetic regulation of PD-L1 expression. Additionally, the correlation between CD274 transcript levels and copy-number alterations (CNA) in primary BC was weak. Pharmacological treatment with either Myc (expressed in MDA-MB-231) or mTOR (p-rpS6 expressed in all three cell lines) inhibitors did not affect PD-L1 expression. STAT3 protein was expressed in all cell lines and STAT3 mRNA levels had a weak positive correlation with PD-L1 (Spearman’s rho = 0.25) in the TCGA dataset. Both gene silencing using STAT3 siRNA and pharmacologic inhibition of STAT3 activity resulted in decreased PD-L1 protein levels in BT549 and MDA-MB-231 cells respectively. Multiple DNA binding sites for STAT3 were identified in silico on the PD-L1 gene promoter suggesting that the observed regulatory effects are likely transcriptional. Conclusions: STAT3 can act as an inducer of PD-L1 expression, while Myc and mTOR seem to have no effect in PD-L1 regulation in BC.
Abstract 12771: A Novel Rotational Speed Modulation System Used With an Implantable Continuous-flow Left Ventricular Assist Device Provides Good Pulsatility on Peripheral Organ Perfusion
Authors: Noritsugu Naito, Takashi Nishimura, Kei Iizuka, Yoshiaki Takewa, Minoru Ono, Eisuke Tatsumi
Journal: Circulation (2016)

Introduction: Continuous-flow left ventricular assist devices (CFLVAD) is widely used to treat patients with end-stage heart failure. Even though the continuous flow is not physiologic, outcomes of CFLVAD have been improved. We have developed a novel rotational speed (RS) modulation system used with CFLVAD (EVAHEART), which can change RS in synchronization with the native cardiac cycle. We have reported that the system can change cardiac load and optimize coronary artery flow. We conducted the present study to investigate the influence of our system on peripheral perfusion. Methods: We implanted EVAHEART devices by the left ventricular apex drainage and the descending aortic perfusion via left thoracotomy in seven adult goats (56.8 ± 8.1 kg). Cardiogenic shock was induced by a beta adrenergic antagonist and coronary artery ligations. We evaluated blood flow, pulsatility index (PI), and maximum time derivative of flow rate (max dQ/dt) of carotid artery (CA), mesenteric artery (MA), renal artery (RA), respectively, using ultrasonic flow meters directly placed on the arteries. Mean tissue blood flow (TBF) of the heart and omentum and PIs of TBF were measured using the TBF meter. Venous lactate level, cerebral oxygen extraction rate (ExO2) and regional saturation of oxygen (rSO2) of brain, kidney, and leg muscle were also evaluated. Those data were collected with a bypass rate of 100% under four conditions: circuit clamp, continuous mode (constant RS), co-pulse mode (increase RS during systole), and counter-pulse mode (increase RS during diastole). Results: PIs of CA and RA in the copulse mode were significantly higher than those in the other modes. Max dq/dt of CA and MA were significantly higher in the copulse mode than those in the counter-pulse mode. Max dq/dt of the three arteries in the copulse mode tended to be higher than those in the other modes. PIs of TBF of the heart and the omentum in the copulse mode tended to be higher than those in the other modes. As for the metabolic changes in each mode, there were no significant differences in levels of lactate, cerebral ExO2, or rSO2. Conclusions: The copulse mode of our novel RS modulation system may provide better pulsatility not only in the large vessels but also in the peripheral perfusion.
Psychiatric Comorbidities Are Associated with Increased Cost of Care and Healthcare Utilization in Multiple Myeloma (MM) Patients
Authors: Shehzad Niazi, Ryan D Frank, Mayank Sharma, Vivek Roy, Steve Ames, Aaron Spaulding, Gerardo Colon-Otero, Asher A. Chanan-Khan, Sikander Ailawadhi
Journal: Blood (2016)
SAT0109 Quantitative estimates of damage and distress, in addition to inflammation, and the proportion each of the 3 variables affects clinical management decisions (total=100%) may clarify assessment of clinical status in patients with rheumatoid arthritis (RA)
Authors: KA Gibson, I Castrejon, T Pincus
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Quantitative assessment in rheumatoid arthritis (RA) is directed to inflammatory activity (INF) and not to joint damage (DAM) and distress (STR - seen as fibromyalgia, depression, etc.). However, DAM and STR may affect clinical management and outcomes of treatment in many RA patients. For example, an RA patient with well-controlled INF who has secondary fibromyalgia may have 0 swollen joints (SJC) and an ESR≥ of 15, but nonetheless have a DAS28 of 5.1, CDAI of ≥22, and RAPID3 of ≥16 (indicating high activity), based on 14/28 tender joints and a patient global assessment of 80/100. Therefore, quantitative estimates of DAM, and STR, as well as INF may clarify patient status and clinical management decisions. <h3>Objectives</h3> To analyze physician quantitative estimates for the proportion of management decisions attributed to INF, DAM, or STR (total=100%) in RA patients seen in routine care. <h3>Methods</h3> At one academic rheumatology center, the rheumatologist completes four 0–10 visual analog scales (VAS) for overall global assessment (DOCGL), INF, DAM, and STR. In patients with DOCGL ≥2, the proportion of management decisions are estimated as %INF+%DAM+%STR=100%. Cross-tabulations were computed for various phenotypes in 5 INF+DAM and INF+STR categories, 0, 1–20%, 21–40%, 42–60%, and 61–100%. <h3>Results</h3> Among the 77 RA patients, &gt;40% of clinical management decisions were attributed to INF in only 31 (40%), versus &gt;40% to DAM in 33 (43%), and &gt;40% to STR in 17 (22%) (Table). No category of INF+DAM or INF+STR included more than 20% of the patients, and patients were found in 17 of 25 possible categories for combinations of INF+DAM and INF+STR. The 13 patients (17%) in whom INF was estimated to contribute 0% to management included 3 of 5 DAM and 5 of 5 STR categories (Table). The 23 patients with 1–20% of management attributed to INF included 4/5 DAM and 5/5 STR categories. The 10 with 21–40% INF included 4/5 DAM and 4 STR categories. The 16 with 41–60% attributed to INF included 3 DAM and 2 STR categories. Only 15 of the 77 patients (19%) had &gt;60% attributed to INF. <h3>Conclusions</h3> Quantitative physician estimates of the proportion of clinical management decisions attributed INF, DAM, and STR may help clarify RA patient status and document a basis for clinical decisions. High levels of DAM and/or STR may explain in part why a target of RA remission often is not met in many patients seen in routine clinical care.<sup>1</sup> <h3>References</h3> Tymms et al, Arth Care &amp; Res 66:190–196, 2014. <h3>Disclosure of Interest</h3> K. Gibson: None declared, I. Castrejon: None declared, T. Pincus Shareholder of: Health Report Services, Inc
SAT0137 Bone mineral density measurement intervals for seropositive rheumatoid arthritis patients not treated for osteoporosis
Authors: W Park, K-H Jung, S-R Kwon, M-J Lim, S-G Park, M-J Jo
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoporosis occurs more frequently in rheumatoid arthritis (RA) patients than in healthy individuals. However the appropriate interval for the bone mineral density (BMD) measurement in RA patients is not well established. <h3>Objectives</h3> This study investigated the effective BMD measurement interval and the risk factors associated with the development of osteoporosis for RA patients. <h3>Methods</h3> A retrospective study was performed on 511 RA patients aged more than 40 years old who had undergone BMD (DXA, GE LUNAR PRODIGY ADVANCE) testing more than once and who had normal BMD or osteopenia at the baseline BMD test and no history of any fracture of the spine or femur. The subjects were categorized into four subgroups: normal BMD (T-score &gt; -1), mild (-1 ≥ T-score &gt; -1.5), moderate (-1.5 ≥ T-score &gt; -2), and advanced (-2 ≥ T-score &gt; -2.5) osteopenia. The BMD testing interval was defined as the estimated time for 10% of the RA patients to make the transition into osteoporosis without osteoporotic fracture or the administration of any osteoporosis drug. <h3>Results</h3> The observation period was 2,214 patient-years, with an average of 4.3 years. The estimated BMD testing interval was more than 10 years for normal, 4.3 years for mild, 2.5 years for moderate, and 1.5 years for advanced osteopenia in each of the RA patient groups. <h3>Conclusions</h3> Our study indicated that in normal or osteopenic RA groups, a baseline BMD T-score is the most important factor in estimating the interval in which osteoporosis is predicted to occur. In addition, we recommend that the BMD measuring interval should be greater than 10 years in normal BMD RA patients, 4 years in mild, 2 years in moderate, and 1 year in advanced osteopenic RA patients on the basis of L-spine BMD. <h3>Disclosure of Interest</h3> None declared
Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B-cell precursor acute lymphoblastic leukaemia: results of the EORTC CLG 58881 and 58951 trials
Authors: C Piette, S Suciu, E Clappier, Y Bertrand, S Drunat, S Girard, K Yakouben, G Plat, N Dastugue, F Mazingue, N Grardel, N van Roy, A Uyttebroeck, V Costa, O Minckes, N Sirvent, P Simon, P Lutz, A Ferster, C Pluchart, M Poirée, C Freycon, M-F Dresse, F Millot, C Chantrain, J van der Werff ten Bosch, K Norga, C Gilotay, P-S Rohrlich, Y Benoit, H Cavé
Journal: Leukemia (2017)
Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities
Authors: Colleen T. Curley, Natasha D. Sheybani, Timothy N. Bullock, Richard J. Price
Journal: Theranostics (2017)

Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies.Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems.With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy.Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system.One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue.When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma.Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue.In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease.We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings.Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area.