tbuckley/cabot-search huggingface dataset:
MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1
Authors: Rui Baptista, Carla Marques, Steve Catarino, Francisco J Enguita, Marina C Costa, Paulo Matafome, Mónica Zuzarte, Graça Castro, Abílio Reis, Pedro Monteiro, Mariano Pêgo, Paulo Pereira, Henrique Girão
Journal: Cardiovascular Research (2017)

MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary hypertension (PH), a multifactorial and progressive condition associated with an increased afterload of the right ventricle leading to heart failure and death. The main aim of this study was to correlate the levels of miR-424(322) with the severity and prognosis of PH and with right ventricle hypertrophy progression. Additionally, we intended to evaluate the mechanisms and signalling pathways whereby miR-424(322) secreted by pulmonary arterial endothelial cells (PAECs) impacts cardiomyocytes.Using quantitative real-time PCR, we showed that the levels of circulating miR-424(322) are higher in PH patients when compared with healthy subjects. Moreover, we found that miR-424(322) levels correlated with more severe symptoms and haemodynamics. In the subgroup of Eisenmenger syndrome patients, miR-424(322) displayed independent prognostic value. Furthermore, we demonstrated that miR-424(322) targets SMURF1, through which it sustains bone morphogenetic protein receptor 2 signalling. Moreover, we showed that hypoxia induces the secretion of miR-424(322) by PAECs, which after being taken up by cardiomyocytes leads to down-regulation of SMURF1. In the monocrotaline rat model of PH, we found an association between circulating miR-424(322) levels and the stage of right ventricle hypertrophy, as well as an inverse correlation between miR-424(322) and SMURF1 levels in the hypertrophied right ventricle.This study shows that miR-424(322) has diagnostic and prognostic value in PH patients, correlating with markers of disease severity. Additionally, miR-424(322) can target proteins with a direct effect on heart function, suggesting that this miRNA can act as a messenger linking pulmonary vascular disease and right ventricle hypertrophy.
Role of gallium-67 scintigraphy in the evaluation of occult sepsis in the medical ICU
Authors: Wei-Chun Chen, Chia-Hung Chen, Wei Chen, Yao-Ling Lee, Chuen-Ming Shih
Journal: European Respiratory Journal (2012)

Patients in intensive care units (ICUs) frequently have multiple infections or persistent fever despite management. This study was to evaluate the diagnostic contribution of gallium-67 scintigraphy in ICU patients with suspected occult sepsis. One hundred and seventeen patients who had undergone gallium-67 scintigraphy in the ICU of our medical center over a 3-year period were retrospectively reviewed and analyzed. Patients were categorized into Group 1 (n = 84), those with a known infectious source, but who still had persistent fever or sepsis despite antibiotic treatment or abscess drainage; or Group 2 (n = 33), those without an evident infectious source after clinical, physical, and imaging studies. Among these patients, 19 (16.2%) had a new diagnosis. In Group 1, 12 patients (14%) had a new infection, including pneumonia (4 patients), bed sore infection (2 patients), pulmonary tuberculosis (2 patients), leg cellulitis (1 patient), psoas muscle abscess (1 patient), osteomyelitis (1 patient), and infective endocarditis (1 patient). In Group 2, seven patients (21.2%) had a new infectious source, including septic arthritis (3 patients), osteomyelitis (2 patients), neck abscess (1 patient), and cholecystitis (1 patient). Gallium-67 scintigraphy helped to detect new or additional infectious sites, particularly bone, joint, and soft tissues.
FRI0295 High risk of idiopathic osteonecrosis in sle patients with high antiphospholipid score and hypertriglyceridemia
Authors: R Hisada, M Kato, N Ohnishi, M Kono, S Tanimura, E Sugawara, H Nakamura, K Ohmura, S Shimamura, Y Fujieda, K Oku, T Bohgaki, O Amengual, S Yasuda, T Atsumi
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Systemic lupus erythematosus (SLE) patients are prone to develop idiopathic osteonecrosis (ION) compared to other connective tissue disease patients or healthy subjects. ION has been shown to occur as a result of ischemia, however, the involvement of antiphospholipid antibodies (aPL) in its pathophysiology remains to be elucidated. In the last years, our group introduced a quantitative marker of aPL "antiphospholipid score (aPL-S)", which well reflected the risk of developing thrombosis [1]. <h3>Objectives</h3> We aimed to identify the impact of aPL on the development of ION using aPL-S. <h3>Methods</h3> A single center retrospective study comprising 82 consecutive patients who were diagnosed SLE at the Rheumatology department of Hokkaido University Hospital and underwent magnetic resonance imaging (MRI) of hip joints from January 2000 to December 2016. Among all the enrolled patients, aPL-S, which is calculated from 0 to 86, as well as classical risk factors for ION were evaluated. <h3>Results</h3> All 82 patients (13 males and 69 females) were given glucocorticoids. ION of the femoral head was diagnosed by MRI scan in 37 patients. Male (ION(+): ION(-) 10/37 (27%) vs 3/45 (7%), p=0.016), malar rush (ION(+): ION(-) 22/37 (59%) vs 16/45 (36%), p=0.045), aPL positivity (ION(+): ION(-) 22/37 (59%) vs 15/45 (33%), p=0.026), high aPL-S (&gt;30) (ION(+): ION(-) 9/37 (24%) vs 3/45 (7%), p=0.031), hypertriglyceridemia (fasting triglyceride levels &gt;150 mg/dL) (ION(+): ION(-) 23/37 (62%) vs 12/45 (27%), p=0.002) and high dose of glucocorticoids (equivalent to 0.8mg/kg or more prednisolone) (ION(+): ION(-) 34/37 (92%) vs 21/45 (47%), p&lt;0.001) were identified as risk factors for ION at univariate analysis. Multivariate analysis confirmed high aPL-S (OR 5.27; 95% CI 1.08 to 34.52, p=0.040), hypertriglyceridemia (OR 5.66; 95% CI 1.79 to 20.73, p=0.003) and high dose of glucocorticoids (OR 16.11; 95% CI 4.01 to 92.54, p&lt;0.001) as independent variables. Of note, in 6 patients who had both high aPL-S and hypertriglyceridemia, 83% (5/6) developed ION (Figure 1). Conversely, systemic lupus erythematosus disease activity index and pulsed methylprednisolone therapy were not identified as risk factors for ION. <h3>Conclusions</h3> We newly identified high aPL-S as a risk factor for ION. Furthermore, SLE patients who have both high aPL-S and hypertriglyceridemia are at very high risk of ION. These findings suggest the involvement of microvascular occlusion in the pathophysiology of ION in SLE. <h3>References</h3> Otomo K, et al. Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. Arthritis Rheum. 2012. <h3>Disclosure of Interest</h3> None declared
THU0704 Evaluation of the accuracy of hand and foot mri in the early identification of ra: using the prevalence of low-graded inflammation in the symptom-free population as reference reduces false-positive mri results
Authors: AC Boer, LE Burgers, L Mangnus, RM Ten Brinck, WP Nieuwenhuis, HW Van Steenbergen, M Reijnierse, TW Huizinga, AH van der Helm van Mil
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Early identification of rheumatoid arthritis (RA) is important, because it allows early treatment initiation and is associated with better disease outcomes. In this perspective, the use of hand and foot MRI in the diagnostic process of rheumatoid arthritis (RA) has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. However, the diagnostic value of MRI is still undetermined. Most studies focussed on the sensitivity rather than the specificity of inflammation detected on MRI. It is known that symptom-free persons can also show inflammation on MRI. Consequently, it has been questioned if MRI-findings in symptom-free volunteers are relevant to consider as a reference when defining a "positive MRI". <h3>Objectives</h3> To determine the value of considering MRI-findings in a control group for the predictive accuracy of MRI when defining a positive MRI. <h3>Methods</h3> 225 patients with CSA and 201 patients with UA underwent MRI of MCP-, wrist- and MTP-joints at baseline and were followed for 1 year on progression to arthritis and RA respectively. MRI was considered positive either if ≥1 joint showed inflammation (called "uncorrected definition"), or if ≥1 joint had inflammation that was present in &lt;5% of persons of the same age-category at the same location in a symptom free reference population (called "5% corrected definition"). MRI scans were scored according to RAMRIS method. Test characteristics were compared for both definitions, hence with and without the incorporation of a reference population when defining a "positive MRI". <h3>Results</h3> By using MRI-data of symptom-free volunteers as reference, the specificity of MRI-detected inflammation increased from 22% to 56% in CSA-patients, and from 10% to 36% in UA-patients. The sensitivity was not affected; it was 88% and 85% in CSA-patients and 93% and 93% in UA-patients. The accuracy also increased, from 32% to 60% in CSA-patients and 22% to 44% in UA-patients. <h3>Conclusions</h3> The use of a reference population resulted in a substantial reduction of false-positive results, without affecting the sensitivity. This is of high importance because of the potential risks of false-positive MRI-results, for example in the setting of UA as a positive MRI-result may influence the decision to initiate disease modifying medication. Although a reference population is generally used in medicine for other tests to derive a definition of a positive test result, this is the first study demonstrating the value of a reference population to define a "positive MRI". <h3>Disclosure of Interest</h3> None declared
SAT0698 Disease activity during and after pregnancy in women with axial spondyloarthritis
Authors: K Ursin, S Lydersen, J Skomsvoll, M Wallenius
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Studies on disease activity of ankylosing spondylitis in pregnancy have shown diverging results. A large retrospective study from 1998 without validated disease activity scores found no particular pattern of disease course during pregnancy (1). Later two small studies demonstrated a tendency towards lower disease activity in the beginning of pregnancy and deterioration in late pregnancy (2,3). None of these studies included women with non-radiographic axial spondyloarthritis. The only large study was conducted before the widespread use of biological DMARDs. <h3>Objectives</h3> The aim of this project was to prospectively study disease activity in women with axial spondyloarthritis before, during and after pregnancy with BASDAI as disease activity measure. <h3>Methods</h3> RevNatus is a Norwegian nationwide register designed for the follow-up of pregnant women with rheumatic diseases. RevNatus included 181 full term pregnancies in 168 women with axial spondyloarthritis between 2006 and 2016. The women had seven visits at a rheumatology unit; before pregnancy, in each trimester, and six weeks, six months and twelve months postpartum. BASDAI-values from each visit were analyzed in a linear mixed model. <h3>Results</h3> Even though we found a statistically significant relationship between disease activity and time point in the follow-up period, our study demonstrated that women with axial spondyloarthritis had stable, low disease activity during and after pregnancy. Disease activity in second trimester was significantly higher than six weeks after delivery, but the change in estimated mean BASDAI was small (BASDAI 3.97 vs. BASDAI 3.46, p=0.005). The figure below shows changes in disease activity throughout the study period. <h3>Conclusions</h3> Studying women with axial spondyloarthritis, we found that disease activity was highest in second trimester, but altogether stable in the period from planning pregnancy to one year after delivery. <h3>References</h3> Ostensen M, Ostensen H. Ankylosing spondylitis - The female aspect. J Rheumatol. 1998;25(1):120–4. Ostensen M, Fuhrer L, Mathieu R, Seitz M, Villiger PM. A prospective study of pregnant patients with rheumatoid arthritis and ankylosing spondylitis using validated clinical instruments. Ann Rheum Dis. 2004;63(10):1212–7. Lui NL, Haroon N, Carty A, Shen H, Cook RJ, Shanmugarajah S, et al. Effect of pregnancy on ankylosing spondylitis: A case-control study. J Rheumatol. 2011;38(11):2442–4. <h3>Disclosure of Interest</h3> None declared
AB0404 Similar remission rates among rheumatoid arthritis patients treated with anti tnf and non-anti tnf therapies: real-life data
Authors: JA Gόmez-Puerta, N Duque, M Saldarriaga, LA González, C Cerόn, L Uribe Botero, OJ Felipe-Díaz
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Several biological DMARD (bDMARD) therapies have been approved for use in rheumatoid arthritis (RA) and are classified according to their respective therapeutic target: Anti TNF therapies and non-Anti TNF therapies. They are very effective in most of patients but their comparative efficacy in daily clinical is less well known. <h3>Objectives</h3> Our aim was to compare the efficacy of anti-TNF therapies vs non-Anti TNF therapies in a cohort of Colombian RA patients followed in different arthritis clinics under daily clinical practice conditions. <h3>Methods</h3> We conducted a cross-sectional study including with RA patients treated at Medicarte IPS from March 2009 to December 2016. Medicarte is a referral center for the integral medical care and pharmaco-surveillance of patients under biologic therapies in 13 cities in Colombia for inflammatory arthropathies, mainly RA, psoriatic arthritis and spondyloartropathies. Clinical information was obtained from electronic clinical records and medical claims. Only those patients with disease activity scores (DAS-28) at baseline and at the last visit were included. Remission was defined as DAS-28 &lt;2.6 on the last visit. Patients treated only with conventional DMARD and/or tofacitinib were excluded. <h3>Results</h3> A total of 1,020 patients with RA were identified. 844 patients (88% female) were included in the final analysis, 416 patients with anti TNF and 428 with non-anti TNF therapies (Rituximab 199, Tocilizumab 125 and Abatacept in 104 patients). The mean age was 55.2±11.8 years, with a mean disease duration of 15.2±9.5 years. bDMARD therapy was used for a mean time period of 3.2±2.5 years. Eighty three percent of patients were treated in combination therapy and 80% of patients were seropositive (CCP and/or RF). Both groups did not differ significantly on baseline clinical characteristics (see Table), with 2 exceptions: patients who received Anti-TNF therapies were treated more frequently as first line therapy (75.2% vs 53.2%, p&lt;0.001) and received in a higher proportion combined therapy (90.9% vs 75.0%, p&lt;0.001). A total of 59% of patient achieved remission at the last visit. Three year remission rates were slightly higher but not significant in patients treated with non-anti TNF therapies vs anti-TNF therapies (59.6% vs 53.3%, p=NS). We did not find significant differences in remission rates according serological status. <h3>Conclusions</h3> In real-life setting, a meaningful proportion of RA patients achieved remission on the last visit. Patients treated with anti-TNF and non-anti TNF therapies had similar baseline characteristics and after a mean time period of treatment of 3 years, achieved similar remission rates. <h3>Disclosure of Interest</h3> None declared
THU0308 Extensive analysis of T cell receptor gamma (TCRG) gene rearrangements reveals a similar repertoire in eosinophilic granulomatosis with polyangiitis (EGPA) and in hypereosinophilic syndrome (HES)
Authors: C Baldini, S Galimberti, E Ciabatti, I Petrini, G Tarrini, M Latorre, E Elefante, F Ferro, R Grossi, N Pisanti, M Petrini, M Mosca
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Hypereosinophilia-associated syndromes are a heterogeneous group of diseases characterized by sustained and elevated blood eosinophilia with evidence of eosinophil-induced organ damage. Classically, Eosinophilic granulomatosis with polyangiitis (EGPA) and Hypereosinophilic syndrome (HES) present several overlapping clinical and laboratory features, making it challenging to correctly insert patients in restricted and well-defined categories with specific and more effective therapeutic approaches. Therefore, great efforts are ongoing searching for novel biomarkers able to differentiate these two disorders in daily practice. <h3>Objectives</h3> To detect T cell receptor gamma (TCRG) clonal rearrangements in EGPA and HES, comparing the frequency distribution of V region and J region segment utilization in the study population. <h3>Methods</h3> In this single center study, we included consecutive patients with a diagnosis of EGPA and HES. Inclusion criteria were: documentation of a persistent peripheral eosinophilic count of ≥1.5 x109/L and signs or symptoms of organ involvement. Clinical and laboratory data of the patients were collected. Sequence-based determination of the frequency distribution of TCRG Gene Rearrangements was performed using next-generation sequencing with the Illumina MiSeq (LymphoTrack TRG assay, Invivoscribe). <h3>Results</h3> We included 21 patients (9 with EGPA and 12 with HES). Four EGPA patients were MPO-ANCA positive. We detected TCRG clonal rearrangements in 44% (4/9) patients with EGPA and in 42% (5/12) patients with HES (p-value = n.s). No association was observed between TCRG clonal rearrangements and ANCA status in EGPA patients. Recurrent TCRG gene rearrangements were observed; in particular, Vg10JgP1 (5 cases) and Vg4Jg1/2 (4 cases) were detected in both EGPA and HES, whereas Vg9Jg1/2 (2 cases) and Vg10Jg1/2 (2 cases) were found only in patients with HES. <h3>Conclusions</h3> Even if preliminary, this study reveals a similar T cell receptor gamma repertoire in EGPA and HES, thus suggesting a possible antigen-driven inflammatory response underlying hypereosinophilia in both EGPA and HES. Moreover, our results would suggest that the TCR clonality cannot be used as a tool for the differential diagnosis between EGPA and HES. <h3>Disclosure of Interest</h3> None declared
Antipsychotics to Treat Agitation or Psychosis in Patients With Dementia
Authors: Daniel Yohanna, Adam S. Cifu
Journal: JAMA (2017)

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Biologically active quinoline and quinazoline alkaloids part I
Authors: Xiao‐Fei Shang, Susan L. Morris‐Natschke, Ying‐Qian Liu, Xiao Guo, Xiao‐Shan Xu, Masuo Goto, Jun‐Cai Li, Guan‐Zhou Yang, Kuo‐Hsiung Lee
Journal: Medicinal Research Reviews (2017)

Quinoline and quinazoline alkaloids, two important classes of N-based heterocyclic compounds, have attracted tremendous attention from researchers worldwide since the 19th century. Over the past 200 years, many compounds from these two classes were isolated from natural sources, and most of them and their modified analogs possess significant bioactivities. Quinine and camptothecin are two of the most famous and important quinoline alkaloids, and their discoveries opened new areas in antimalarial and anticancer drug development, respectively. In this review, we survey the literature on bioactive alkaloids from these two classes and highlight research achievements prior to the year 2008 (Part I). Over 200 molecules with a broad range of bioactivities, including antitumor, antimalarial, antibacterial and antifungal, antiparasitic and insecticidal, antiviral, antiplatelet, anti-inflammatory, herbicidal, antioxidant and other activities, were reviewed. This survey should provide new clues or possibilities for the discovery of new and better drugs from the original naturally occurring quinoline and quinazoline alkaloids.
Tipping Point for Patent Foramen Ovale Closure
Authors: Allan H. Ropper
Journal: New England Journal of Medicine (2017)

On the basis of what I had read previously in the Journal, I recently explained to my 44-year-old patient that closing his patent foramen ovale (PFO) after his stroke was not advisable. How can we now have three trials showing that closure prevents recurrent stroke, given that in the past 5 years, the Journal published articles from three other trials that showed the opposite? It would be simple if the conversion from a negative to a positive outlook with respect to PFO closure could be explained by studying the various antiplatelet and anticoagulant treatments, or the various durations of follow-up . . .