tbuckley/cabot-search huggingface dataset:
SP0006 Looking back at 70 years of eular and 30 years of hp involvement: a nursing perspective
Authors: J Hill
Journal: Annals of the Rheumatic Diseases (2017)

At the 1987 EULAR Congress held in Athens, a British nurse, Vicky Stephenson, arranged a meeting that was attended by about 30 health professionals. The meeting decided that a working group of Health Professionals from different professions and countries should work towards establishing a Standing Committee within EULAR. This was achieved in 1989 and since that time, the role of Health Professionals within EULAR has changed dramatically. In this lecture, I will describe the evolution of rheumatology nursing over the past thirty years, and the part that EULAR has played in the dissemination, education and facilitation of best nursing practice and experiences within Europe. This will be illustrated by two pieces of work. In late 2009, EULAR part funded a Web-based survey to evaluate the status of extended roles undertaken by health professionals in Europe. The data from this survey relating to nursing has been extracted and analysed separately and will be presented. The following year, EULAR also funded a study to investigate the role of the nurse in the management of chronic inflammatory arthritis. The important recommendations resulting from this piece of work will also be shown. Following the recommendations project, a number of other important nursing initiatives have been launched under the auspices of EULAR. These will be highlighted to enable delegates to understand how far rheumatology nursing has developed and how far it still has to go. <h3>Disclosure of Interest</h3> None declared
Neuroendocrine tumors (NET) of the gastrointestinal tract: Experience at Winship Cancer Institute of Emory University.
Authors: Syed Farhan Zafar, Dattatraya Hari Patil, John S. Kauh, Volkan Adsay, David A. Kooby, Edith Brutcher, Shishir Kumar Maithel, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2012)

e14692 Background: NET are relatively uncommon malignancies with variable natural history and often indolent clinical behavior. Pancreatic neuroendocrine tumors (PNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract other than pancreatic (GNET). The objective of our study was to compare the clinicopathologic characteristics, presentation, treatment and survival outcomes in PNET and GNET. Methods: After IRB approval, we identified 125 patients (pts) with NET of the gastrointestinal tract from 2006-2011 in the Winship Institute cancer registry. A retrospective chart review was performed. Patients were categorized in mutually exclusive groups of PNET and GNET. Results: Demographic information and comparison of basic characteristics are listed in the table. Treatment modalities employed for PNET included surgery (72%), chemotherapy (30%), biological therapy (13%) and somatostatin analogues (11%). Liver-directed therapies were employed for hepatic metastases in 9 pts with PNET. Most common modality was radiofrequency ablation (4 pts) followed by Yttrium-90 embolization (3 pts), chemoembolization (1 pt) and bland embolization (1 pt). Majority of GNET were of midgut origin (47%) followed by foregut (35%) and hidgut (13%). Treatment for GNET included surgery (64%), chemotherapy (11%) and somatostatin analogues (17%). 90% of pts in PNET and 89% in GNET were alive at median follow up of 82 months. Conclusions: Overall, pts with NET have good prognosis. In our series, patients with PNET and GNET, had comparable survival outcomes even in advanced stage. These patients should be evaluated by a multidisciplinary team as new therapies become available. [Table: see text]
AB1216-HPR The effects of application of iontophoresis and phonophoresis in patients with subacromial impingement syndrome
Authors: A Yildiz, E Kusan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Subacromial impingement syndrome (SIS) is defined as the mechanical compression of subacromial structures between the coraco-acromial arch and the humerus during active elevation of the arm above shoulder height. <h3>Objectives</h3> The aim of the study was to investigate the effects of applications of iontophoresis and phonophoresis, which has been used in addition to physiotherapy program on pain and disability level in patients with SIS. <h3>Methods</h3> The study was conducted with subjects (n=43) diagnosed with SIS. The subjects were divided into two groups randomly as iontophoresis group (IG) and phonophoresis group (PG). Diclofenac sodium iontophoresis was applied to the first group (n=22), diclofenac sodium phonophoresis was applied to the second group (n=21). In addition all of groups therapy program includes superficial heat, transcutaneous electrical nerve stimulation and exercise. The groups were evaluated before and after treatment in terms of pain and scores of shoulder disability. Visual analog scale was used to assess of pain (night pain, rest pain, pain with motion and pain in functional use), Shoulder Disability Questionnaire (SDQ) and Disabilities of the Arm Shoulder and Hand (DASH) were used to assess of shoulder disability. <h3>Results</h3> 43 patients with IS aged 18 to 65 years were recruited to the study. Demographic data were similar in the groups. After treatments pain severity (night pain and pain in functional use) was significantly decreased in both groups (p&lt;0,05) and in the scores of disability of shoulder (p&lt;0,05) in both groups. Pain relief was similar in groups. SDQ and DASH scores were improved in two groups after treatments. But there was no difference between the groups in terms of functionality and disability scores. <h3>Conclusions</h3> This study shows that diclofenac sodium iontophoresis and phonophorosis that are used in patients with subacromial impingement syndrome have similar positive therapeutic effects on shoulder functions. <h3>References</h3> Kuhn JE. Exercise in the treatment of rotator cuff impingement: a systematic review and a synthesized evidence-based rehabilitation protocol. J Shoulder Elbow Surg. 2009 Apr;18(1):138–60. Sedeek SM et al. Subacromial impingement syndrome: review article. Hard Tissue 2013 Sep 28;2(4):39–43. Ozsahin M et al. Adaptation of the Shoulder Disability Questionnaire to the Turkish population, its reliability and validity. International Journal of Rehabilitation Research. 2008;31(3):241–45. Düger et al. Kol, omuz ve el sorunları anketi (Disabilities of the Arm, Shoulder and Hand – DASH) Türkçe uyarlamasının güvenirliği ve geçerliği. Fiyoter Rehabil. 2006;17(3):99–107. <h3>Disclosure of Interest</h3> None declared
A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors
Authors: Julia E Neumann, Annika K Wefers, Sander Lambo, Edoardo Bianchi, Marie Bockstaller, Mario M Dorostkar, Valerie Meister, Pia Schindler, Andrey Korshunov, Katja von Hoff, Johannes Nowak, Monika Warmuth-Metz, Marlon R Schneider, Ingrid Renner-Müller, Daniel J Merk, Mehdi Shakarami, Tanvi Sharma, Lukas Chavez, Rainer Glass, Jennifer A Chan, M Mark Taketo, Philipp Neumann, Marcel Kool, Ulrich Schüller
Journal: Nature Medicine (2017)
Abstract 28: In Vivo Knockdown of Mirna-15b Results in Increased Cardiac Hypertrophy and Fibrosis in Response to Pressure Overload of the Mouse Heart
Authors: Anke J Tijsen, Ingeborg van der Made, Elza D van Deel, Monika Hiller, Yolan J Reckman, Dirk J Duncker, Yigal M Pinto, Esther E Creemers
Journal: Circulation Research (2012)

MiRNAs play an important role in the control of diverse aspects of cardiac function. MiR-15b is highly expressed in the heart and is found consistently upregulated in hypertrophic and failing hearts. To investigate the function of miR-15b in the heart we set out two experiments. In the first experiment we generated two independent transgenic mouse lines that drive miR-15b expression under the αMHC-promotor and show a three and four fold overexpression of miR-15b. Strikingly, both lines show a decrease in heart weight/tibia length of 20% in adult and aged mice when compared to littermate controls. We investigated the response of these transgenic mice to thoracic aorta constriction (TAC) and found no differences in the hypertrophic response or in cardiac function measured by echocardiography between wild-type and transgenic mice. In a second experiment, we inhibited miR-15b using LNA-based antimiRs. In these mice, TAC resulted in an increased hypertrophic response and increased cardiac fibrosis when compared to a negative control antimiR. A wide range of predicted targets of miR-15 belong to the pathways of the TGFβ-superfamily and using a smad-dependent reporter we show that miR-15b inhibits TGFβ-induced Smad activity in HepG2 cells. One of the predicted targets in the TGFβ pathway is TGFβ receptor 1 (TGFβR1), of which the 3’UTR contains six predicted miR-15 binding sites. This suggests that the phenotype in the transgenic mice and after knockdown of miR-15b may be (partly) mediated by repression of TGFβR1. Indeed, in the adult miR-15b transgenic hearts we found a downregulation of TGFβR1 mRNA and protein and we confirmed binding of miR-15 to the TGFβR1 3’UTR by luciferase assays. In conclusion, miR-15b causes a cardiac hypotrophic phenotype at baseline in transgenic mice and inhibition of miR-15b leads to a stronger hypertrophic and fibrotic response after TAC. Furthermore miR-15b inhibits the TGFβ pathway by targeting the TGFβR1 and possibly other targets in this pathway. This research is funded by the Dutch Heart Foundation (NHF grant #2007B077).
FRI0033 Important role of CD11C+ dendritic cells in inflammatory arthritis
Authors: A Puchner, V Saferding, M Bonelli, H Leiss, R Pfeifle, G Kroenke, M Koenders, J Smolen, K Redlich, S Blüml
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Dendritic cells (DCs) are important antigen presenting cells (APCs) and therefore they play an important role in bridging the innate and the adaptive immune response. DCs can be divided in different subsets with specific functions. As powerful APCs, DCs are thought to play an important role in the induction of autoimmune diseases such as rheumatoid arthritis. However, the active role of DCs in joint inflammation is not known yet. <h3>Methods</h3> We analyzed histological sections of K/BxN serum transfer arthritis as well as hTNFtg arthritis for the presence of CD11c<sup>+</sup> cells by immunohistochemistry. We also performed synovial biopsies and analyzed the cellular composition of the inflammatory infiltrate with respect to DCs. We used CD11c-diphteria toxin receptor (DTR) transgenic mice, which express the human diphtheria-toxin receptor under the CD11c promoter, allowing for specific depletion of CD11c<sup>+</sup> cells by administration of diphtheria toxin (DT). K/BxN serum transfer arthritis was induced, and mice were given either DT or PBS or in wt and BARF3 deficient mice. In addition CD11c DTR mice were crossed into hTNFtg animals and also received either DT or PBS. The severity of arthritis was determined clinically and histologically. <h3>Results</h3> We show that Cd11c<sup>+</sup> cells are present in significant numbers in the synovia of K/BxN and TNF driven arthritis. Both CD8<sup>+</sup>CD11c<sup>+</sup> and CD11b<sup>+</sup>CD11c<sup>+</sup>, can be found in synovial tissue. Upon depletion of CD11c+ cells clinical signs of K/BxN serum transfer arthritis were significantly reduced. Histological analysis found reduced synovial inflammation after the depletion of CD11c<sup>+</sup> cells in K/BxN arthritis. In addition, local bone destruction and the number of osteoclasts was also significantly reduced. Analysis of K/BxN arthritis in wt mice and BATF3<sup>-/-</sup> mice, which lack a subset of DCs, namely CD8<sup>+</sup>CD11<sup>+</sup> DCs, revealed no difference in arthritis severity between the two groups. In addition to K/BxN arthritis, we found that also in TNF-driven arthritis depletion of CD11c<sup>+</sup> cells led to a striking reduction of synovial inflammation and a complete depletion of osteoclasts. <h3>Conclusions</h3> These data show that in addition to initiating an adaptive immune response, CD11c<sup>+</sup> dendritic cells, are also involved in innate effector mechanisms of inflammatory arthritis. Especially CD11b<sup>+</sup>CD11c<sup>+</sup> and monocyte derived inflammatory seem to play a role in inflammatory arthritis, suggesting that they could be an important therapeutic target for patients suffering from inflammatory arthritis. <h3>Disclosure of Interest</h3> None declared
The CRASH report: emergency management dilemmas facing acute physicians in patients with pulmonary arterial hypertension
Authors: Laura C Price, Konstantinos Dimopoulos, Philip Marino, Rafael Alonso-Gonzalez, Colm McCabe, Aleksander Kemnpy, Lorna Swan, Maria Boutsikou, Ahmed Al Zahrani, Gerry J Coghlan, Benjamin E Schreiber, Luke S Howard, Rachel Davies, Mark Toshner, Joanna Pepke-Zaba, Alistair C Church, Andrew Peacock, Paul A Corris, James L Lordan, Sean Gaine, Robin Condliffe, David G Kiely, Stephen John Wort
Journal: Thorax (2017)

Treatment of acute emergencies in patients with pulmonary arterial hypertension (PAH) can be challenging. In the UK and Ireland, management of adult patients with PAH is centred in eight nationally designated pulmonary hypertension (PH) centres. However, many patients live far from these centres and physicians in local hospitals are often required to manage PAH emergencies. A committee of physicians from nationally designated PH centres identified the 'most common' emergency clinical scenarios encountered in patients with PAH. Thereafter, a review of the literature was performed centred on these specified topics and a management approach was developed based on best available evidence and expert consensus. Management protocols were developed on the following PAH emergencies: chest pain (including myocardial ischaemia), right ventricular failure, arrhythmias, sepsis, haemoptysis ('CRASH'), as well as considerations relevant to surgery, anaesthesia and pregnancy. Emergencies are not uncommon in PAH. While expertise in PAH management is essential, all physicians involved in acute care should be aware of the principles of acute management of PAH emergencies. A multidisciplinary approach is necessary, with physicians from tertiary PH centres supporting care locally and planning safe transfer of patients to PH centres when appropriate.
Phase II and pharmacogenomics study of enzastaurin plus temozolomide and radiation therapy in patients with glioblastoma multiforme or gliosarcoma
Authors: N. A. Butowski, K. Lamborn, S. Chang, E. Hsieh, A. Fedoroff, R. Parvataneni, S. Nicol, A. Liepa, D. Thornton, M. Prados
Journal: Journal of Clinical Oncology (2009)

2020 Background: ENZ, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCβ and the PI3K/AKT pathways to induce apoptosis, reduce proliferation, and suppress angiogenesis. The primary endpoint of this single-arm phase II trial was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, PK/PD, and patient-reported outcomes (PROs). A concurrent PGx project assessed the value of pretreatment molecular profiles as predictive of outcome. Magnetic resonance spectroscopy (MRS) was also evaluated during treatment for its value in predicting OS. Methods: Patients enrolled with newly diagnosed GBM/GS and KPS ≥60. Treatment started &lt;5 weeks after diagnosis with RT 60 Gy given over 6 weeks and TMZ 75 mg/m 2 given daily during RT and then at 200 mg/m 2 from days 1–5 of a 28-day cycle. ENZ 250 mg/day was given daily during RT and adjuvantly. Planned treatment duration was 1 year. PGx parameters were: MGMT promoter methylation, mismatch repair status, PKC isoforms, pERK, pCREB, EGFR, PTEN, GSK3B, ser9, VEGF, and pS6. MRS was performed at baseline and at scheduled intervals. Changes in molecular signatures and imaging characteristics relative to survival were estimated using Kaplan-Meier and proportional hazards models. Analyses included phase I patients at ENZ 250 mg/day. Results: From September 2007 to November 2008, 60 phase II patients enrolled; 52 completed RT and eight are receiving RT. Of these, seven patients progressed immediately after RT and 17 progressed after one or more adjuvant cycles; five discontinued due to toxicity; four withdrew from trial. Treatment was well tolerated. The only toxicities seen in more than one-third of pateints were grade 1 fatigue, grade 1 nausea, and grade 1–2 lymphopenia. Grade 1 thrombocytopenia was seen in eight patients and grade 3 lymphopenia in five patients. OS, PFS, PROs, PGx, and imaging findings will be reported. Conclusions: The combination of ENZ plus TMZ during and following RT was well tolerated and may be an active regimen in GBM. This study represents the future of neuro-oncology clinical trial design by employing a novel multi-modal therapy while concurrently studying novel imaging and molecular techniques that may predict efficacy. [Table: see text]
Human leukocyte antigen variants and risk of hepatocellular carcinoma modified by hepatitis C virus genotypes: A genome‐wide association study
Authors: Mei‐Hsuan Lee, Yu‐Han Huang, Hsuan‐Yu Chen, Seik‐Soon Khor, Ya‐Hsuan Chang, Yu‐Ju Lin, Chin‐Lan Jen, Sheng‐Nan Lu, Hwai‐I Yang, Nao Nishida, Masaya Sugiyama, Masashi Mizokami, Yong Yuan, Gibert L'Italien, Katsushi Tokunaga, Chien‐Jen Chen
Journal: Hepatology (2017)

We conducted a genome-wide association study to discover genetic variants associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We genotyped 502 HCC cases and 749 non-HCC controls using the Axiom-CHB genome-wide array. After identifying single-nucleotide polymorphism clusters located in the human leukocyte antigen (HLA) region which were potentially associated with HCC, HLA-DQB1 genotyping was performed to analyze 994 anti-HCV seropositives collected in the period 1991-2013 in a community-based cohort for evaluating long-term predictability of HLA variants for identifying the risk of HCC. Cox proportional hazards models were used to estimate the hazard ratios and 95% confidence intervals of HLA genotypes for determining the aforementioned HCC risk. Eight single-nucleotide polymorphisms in the proximity of HLA-DQB1 were associated with HCC (P < 8.7 × 10-8 ) in the genome-wide association study. Long-term follow-up showed a significant association with HLA-DQB1*03:01 and DQB1*06:02 (P < 0.05). The adjusted hazard ratios associated with HCC were 0.45 (0.30-0.68) and 2.11 (1.34-3.34) for DQB1*03:01 and DQB1*06:02, respectively. After stratification by HCV genotypes, DQB1*03:01 showed protective effects only in patients with HCV genotype 1, whereas DQB1*06:02 conferred risk of HCC only in patients with HCV non-1 genotypes. HLA imputation analyses revealed that HLA-DRB1*15:01, which is in linkage disequilibrium with DQB1*06:02, also increased the risk of HCC (odds ratio, 1.96; 95% confidence interval, 1.31-2.93). Haplotype analysis supported that DQB1*03:01 and DQB1*06:02 are primarily protective and susceptible variants, respectively. Conclusion: HLA-DQB1 was independently associated with HCC; HCV genotypes modified the effects of HLA-DQB1 on the risk of HCC. (Hepatology 2018;67:651-661).
AB1135 Allopurinol and the risk of incident peripheral arterial disease in the elderly americans: a u.s. medicare claims data study
Authors: J Singh, J Cleveland
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Recently we found that use of allopurinol, the most commonly used urate-lowering therapy (ULT), was associated with a reduction of the risk of myocardial infarction and stroke, acute manifestations of CAD. Given that both PAD and CAD are manifestations of atherosclerosis and a similarity of disease pathophysiology between them, an obvious question was whether allopurinol use would reduce PAD. To our knowledge, no previous studies have examined whether allopurinol use reduces the risk of PAD. <h3>Objectives</h3> To examine whether new allopurinol use is independently associated with a reduction of the risk of incident peripheral arterial disease (PAD) in the U.S. elderly. <h3>Methods</h3> We used the 5% random Medicare sample from 2006–2012 to examine the association of allopurinol use and its duration with risk/hazard of incident PAD, in a retrospective cohort study. Multivariable Cox regression models adjusted for demographics, comorbidity, cardiac medications and cardiac conditions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. <h3>Results</h3> We identified 26,985 episodes of incident allopurinol use in 25,282 beneficiaries, of which 3,167 allopurinol use episodes (12%) ended in incident PAD. In multivariable-adjusted analyses, allopurinol use was associated with HR of 0.88 (95% CI, 0.81, 0.95) for incident PAD, as was female gender, 0.84 (95% CI, 0.78, 0.90). In a separate multivariable-adjusted model, compared no allopurinol use, longer durations of allopurinol use were associated with lower HR of PAD: 181 days to 2 years, 0.88 (95% CI, 0.79, 0.97) and &gt;2 years, 0.75 (95% CI, 0.63, 0.89). Other factors significantly associated with a higher hazard of PAD were age 75-&lt;85 and ≥85, female gender, higher Charlson index score, and black race. Sensitivity analyses adjusting for cardiac conditions and medications, confirmed these findings with minimal to no attenuation of hazard ratios. <h3>Conclusions</h3> New allopurinol use was independently associated with a lower risk of PAD in the elderly. Longer allopurinol use durations seemed more protective. Mechanisms of protective effect need to be studied in future studies. <h3>Disclosure of Interest</h3> J. Singh Grant/research support from: Takeda and Savient, Consultant for: Savient, Takeda, Regeneron, Merz, Iroko, Bioiberica, Crealta and Allergan pharmaceuticals, WebMD, UBM LLC and the American College of Rheumatology, J. Cleveland: None declared