tbuckley/cabot-search huggingface dataset:
SAT0702 Local and systemic inflammation in patients with early rheumatoid arthritis with chlamydia trachomatis infection
Authors: M Natalia, K Svetlana
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> We had to study local and systemic inflammation in rheumatoid arthritis patients with persistence Chlamydia trachomatis (Ch tr) in the joint <h3>Methods</h3> 31 patients with early RA; mean age 54,5 (10,6) years, disease duration 21,5 (14,4) weeks witch persistence Ch tr in the joint (mRNP Ch tr had been revealed in synovial fluid by NASBA PCR) were enrolled in this study. The comarison group was patients with RA (n=42) without mRNP in synovial fluid (Ch tr-). Mean age was 51,7 (15,4) years, disease duration 20,8 (13,3) weeks. All the patients had been received only symptomatic treatment (NSAID). Disease activity had been detected by DAS 28. Systemic inflammation was estimated by levels of erythrocyte sedimentation rate (ESR), hsp C-reactive protein (hspCRP), orozomucoid (OR) in the blood samples; local inflammation- by detection hsp CRP, OR in synovial fluid. Also we had been detected level of ACCP in the blood samples and synovial fluid. <h3>Results</h3> We didn9t reveal statistically significant differences between levels of ESR, hsp CPR, OR, ACCP in blood samples patients with RA Chtr+ and RA Ch tr-. Level of hsp CPR and OR in synovial fluid of research group (Ch tr+) were significantly higher than comparison group (4,1±0,3 mg/l versus 2,4±0,2 mg/l, p&lt;0,05 –hspCRP and 157,4±17,5mg/dl versus 78,5±18,9 mg/dl, p&lt;0,001- OR). In the group of research (Ch tr+) level of ACCP in synovial fluid was statistically significant higher than comparison group (Ch.tr -) (195,6±37,3 versus 67,9±15,4; p&lt;0,001) <h3>Conclusions</h3> Patients with early RA detected by NASBA PCR in synovial fluid Ch tr+, had been characterized by absence differences compared RA Ch tr- patients in the level of systemic inflammation and had differences in the level of local inflammation. We revealed high level of ACCP in RA patients with Ch tr in the joints, that may be important for understanding some aspects of RA pathogenesis. <h3>Disclosure of Interest</h3> None declared
Targeted inhibition of G <sub>q</sub> signaling induces airway relaxation in mouse models of asthma
Authors: Michaela Matthey, Richard Roberts, Alexander Seidinger, Annika Simon, Ralf Schröder, Markus Kuschak, Suvi Annala, Gabriele M. König, Christa E. Müller, Ian P. Hall, Evi Kostenis, Bernd K. Fleischmann, Daniela Wenzel
Journal: Science Translational Medicine (2017)

Obstructive lung diseases are common causes of disability and death worldwide. A hallmark feature is aberrant activation of Gq protein-dependent signaling cascades. Currently, drugs targeting single G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) are used to reduce airway tone. However, therapeutic efficacy is often limited, because various GPCRs contribute to bronchoconstriction, and chronic exposure to receptor-activating medications results in desensitization. We therefore hypothesized that pharmacological Gq inhibition could serve as a central mechanism to achieve efficient therapeutic bronchorelaxation. We found that the compound FR900359 (FR), a membrane-permeable inhibitor of Gq, was effective in silencing Gq signaling in murine and human airway smooth muscle cells. Moreover, FR both prevented bronchoconstrictor responses and triggered sustained airway relaxation in mouse, pig, and human airway tissue ex vivo. Inhalation of FR in healthy wild-type mice resulted in high local concentrations of the compound in the lungs and prevented airway constriction without acute effects on blood pressure and heart rate. FR administration also protected against airway hyperreactivity in murine models of allergen sensitization using ovalbumin and house dust mite as allergens. Our findings establish FR as a selective Gq inhibitor when applied locally to the airways of mice in vivo and suggest that pharmacological blockade of Gq proteins may be a useful therapeutic strategy to achieve bronchorelaxation in asthmatic lung disease.
AB0601 Anatomic and functional assessment of peripheral perfusion in patients with systemic sclerosis. is there any correlation between capillaroscopic findings and ergospirometry?
Authors: A Sarantopoulos, I Gkougkourelas, A Pataka, I Stanopoulos, I Koulas, P Boura
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Microvasculopathy of systemic circulation in patients with Systemic Sclerosis (SS) is widely assessed by digital capillaroscopy (DC), a method that evaluates the architecture of capillary network and reveals changes of vascular anatomy. On the other hand, ergospirometry (ERG) reveals functional impairment of microcirculation by assessing indirect measures of peripheral tissue ischemia (most suitable VE/VCO2). Since today, there have been studies correlating DC findings with spirometric parameters (respiratory volumes)<sup>1,2</sup>; nevertheless, no reports have been published correlating the same DC findings with ERG parameters (functional microvascular perfusion). <h3>Objectives</h3> To propose the use of DC as a screening tool for impaired functional microvasculopathy by investigating correlations between patterns of capillaroscopic findings with ergospirometric values of peripheral tissue blood perfusion. <h3>Methods</h3> 11 patients (11 women mean age 43+/- 12 ys) with SS were evaluated contemporary with High Resolution Computed Tomography of the chest, ERG, and DC. Parameters were correlated with multiple regression analysis. Statistic significance was considered p&lt;0.05. <h3>Results</h3> Patient data are shown in the table. Patients with late pattern in capillaroscopy had less endurance in exercise test (P&lt;0.05) but no correlation was found between capillaroscopic pattern and VE/VCO2 (P&gt;0.05). Age was a crucial confounding factor. <h3>Conclusions</h3> The correlation of late pattern capillaroscopy findings with reduced ergospirometric endurance in 11 patients indicates that in a larger cohort, specific parameter associations between DC and ERG are probable to emerge. <h3>References</h3> Ghizzoni C, Sebastiani M, Manfredi A, et al. Prevalence and evolution of scleroderma pattern at nailfold videocapillaroscopy in systemic sclerosis patients: Clinical and prognostic implications. Microvasc Res. 2015 May; 99: 92–5. Castellví I, Simeόn-Aznar CP, Sarmiento M, et al. Association Between Nailfold Capillaroscopy Findings and Pulmonary Function Tests in Patients with Systemic Sclerosis. J Rheumatol. 2015 Feb; 42(2): 222–7. <h3>Disclosure of Interest</h3> None declared
AB0564 Temporal arteritis: is there any correlation between ultrasonographic arterial wall involvement and the inflammatory cellular infiltrate at histological examination?
Authors: G Germano, PL Macchioni, A Cavazza, L Cimino, F Muratore, C Salvarani
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Ultrasonographic alterations such as the halo sign and the compression test are now accepted as surrogate markers of artery inflammation. No data have yet been published on the correlation between the ultrasonographic grading of arterial wall inflammation and the grading of cellular infiltrate. <h3>Objectives</h3> To compare a semiquantitative ultrasonographic grading (USG) of TA involvement (halo sign and media-intima thickness) with a semiquantitative grading of the inflammatory burden in patients with giant cell (temporal) arteritis (GCA). <h3>Methods</h3> Fiftheen consecutive patients with new onset clinical symptoms and satisfiing ACR criteria for GCA, with positive halo sign in the frontal branch and positive temporal artery biopsy have been enrolled. For each patients we performed power Doppler ultrasonography of temporal artery with a 18–6 MHz linear probe (Esaote MyLab 70) and measured the maximum halo thickness of TA frontal branch in a quantitative and semiquantitave (0–3) grade of involvement (0 = &lt;0.37 mm, 1 = in between 0.38–0.44, 2 = 0.45–0.6 mm, 3 = &gt;0.6). TA biopsy was done in the same frontal branch evalutaed with US. Then we compared the ultrasonographic data with a semiquantitative (0: absent, 1: mild, 2: moderate, 3: severe) grading of the trasmural cellular inflammatory infiltrate and with the intima-media thickness of the TA biopsy specimen. Moreover US results were correlated with the other patterns of histological alterations (giant cells, calcifications, laminar necrosis). Correlation between variables was done by Rho of Spearman method. <h3>Results</h3> 15 patients, 6 males and 9 females (mean age 71.6±7 years – duration symptoms at onset 1.7±1.3 months – mean ESR 60 mm/h ±29 – mean CRP 8 mg/dl ± 5.2) entered the study. US halo sign was bilateral in 10/15 (66,7%). The mean halo thickness was 0.53 mm ± 0.12. Five patients had USG =1, six patients =2 and four patients =3. The hystological inflammatory grade 1 was present in seven pts, grade 2 in four and grade 3 in four pts. No significant correlation were found between USG and histological inflammatory grade, nor with the presence of giant cells, calcifications, laminar necrosis and intima-media thickness. <h3>Conclusions</h3> No correlation has been found between the size of the halo sign and the hystological inflammatory grading. <h3>Disclosure of Interest</h3> None declared
AB0774 Prevalence, clinical and radiographic characteristics of sacroilitis in patients with psoriasis
Authors: L Stefanović, D Veljković, E Mahmutović, V Skakić
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Psoriasis is a skin disorder that is associated with arthritis. Sacroiliac joint involvement is considered to be less frequent than the other types of psoriatic arthritis. <h3>Objectives</h3> im of the study was to investigate the prevalence of sacroilitis in patients with psoriasis (Ps) in region of Kraljevo, Novi Pazar and Niška banja. <h3>Methods</h3> A multicenter, noninterventional, retrospective, cross-sectional study was conducted at 3 care centers in region of Kraljevo, Novi Pazar and Niška banja. Diagnosis of sacroilitis was based on clinical and antero-posterior pelvic X-rays Prevalence of sacroilitis and its clinical and radiologic characteristics were examined. <h3>Results</h3> Sacroilitis was documented in 24/100 (24%) patients with Ps. There was no significant difference in average age between Ps patients without sacroilitis (47,83) and Ps patients with sacroilitis (49,9). Sacroiliitis appeared to be unilateral in 12,5% and bilateral in 87.5% of patients. Ps preceded sacroilitis in 62,50% and sacroilitis preceded Ps in 29,17% of cases; concomitant onset of Ps and sacroilitis was present in 8,33%. Peripheral arthritis was found in 67,89% patients with sacroilitis. <h3>Conclusions</h3> The prevalence of sacroilitis and related spondylitis is high in patient with Ps. We found predominantly bilateral sacroilitis which is characteristic of ankylosing spondylitis. This is in contrast to present knowledge about the association of psoriasis and sacroiliitis. In 68% sacroilitis patients we found associated peripheral arthritis. <h3>Disclosure of Interest</h3> None declared
Epigenetic Modification of MicroRNA-200b Contributes to Diabetic Vasculopathy
Authors: Kanhaiya Singh, Durba Pal, Mithun Sinha, Subhadip Ghatak, Surya C. Gnyawali, Savita Khanna, Sashwati Roy, Chandan K. Sen
Journal: Molecular Therapy (2017)

Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work recognized miR-200b as a critical angiomiR, which must be transiently downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy by epigenetic modification of a miR promoter. In human microvascular endothelial cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and compromised endothelial function as manifested by diminished endothelial nitric oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO production, and compromised VE-cadherin expression. Bisulfite-sequencing documented HG-induced miR-200b promoter hypomethylation in HMECs and diabetic wound-site endothelial cells. In HMECs, HG compromised endothelial function. Methyl donor S-adenosyl-L-methionine (SAM) corrected miR-200b promoter hypomethylaton and rescued endothelial function. In vivo, wound-site administration of SAM to diabetic mice improved wound perfusion by limiting the pathogenic rise of miR-200b. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics and ingenuity pathway analysis identified HG-induced proteins and principal clusters in HMECs sensitive to the genetic inhibition of miR-200b. This work presents the first evidence of the miR-200b promoter methylation as a critical determinant of diabetic wound angiogenesis.
Cirrhotic patients with portal hypertension-related bleeding and an indication for early-TIPS: A large multicentre audit with real-life results
Authors: Dominique Thabut, Arnaud Pauwels, Nicolas Carbonell, Andre Jean Remy, Pierre Nahon, Xavier Causse, Jean-Paul Cervoni, Jean-François Cadranel, Isabelle Archambeaud, Slim Bramli, Florent Ehrhard, Philippe Ah-Soune, Florian Rostain, Alexandre Pariente, Julien Vergniol, Jean-Pierre Dupuychaffray, Anne-Laure Pelletier, Florence Skinazi, Anne Guillygomarc'h, René-Louis Vitte, Jean Henrion, Stéphanie Combet, Marika Rudler, Christophe Bureau, Roland Amathieu, Isabelle Archambeaud, Cécilia D'Arondel de Hayes, Karim Aziz, Hélène Barraud, Guy Bellaïche, Pierre-Olivier Bernard, Bruno Bour, Farah Zerouala Boussarah, Louis Buscail, Karine Chageanu-Derrode, Innocenti Dadamessi, Mathilde David, Thong Dao, François Dewaele, Nina Dib, Laurence Donato, Sylva Doumet, Marie Eccochard, Khaldoun Elriz, Stéphanie Faure, Anne-laure Gillet, Pascal Guivarch, Vincent Jouannaud, Laure Lamare, Yann Le Bricquir, Vincent Leroy, Véronique Lousteau-ratti, Alexandre Louvet, Gilles Macaigne, Stéphanie De Montigny, Eric Nguyen Khac, Violaine Ozenne, Jean-Louis Payen, Agnès Pélaquier, Jean-Marc Perarnau, Aurélie Plessier, Dr Joanna Pofelski, Ghassan Riachi, Jacques-Arnaud Seyrig, Faouzi Saliba, Philippe Sogni
Journal: Journal of Hepatology (2017)
Randomized, double-blind, phase 3 study evaluating efficacy and safety of ABP 215 compared with bevacizumab in patients with non-squamous NSCLC.
Authors: Nick Thatcher, Michael Thomas, Luis Paz-Ares, Gyula Ostoros, Zhiying Pan, Jerome H. Goldschmidt, Vladimir Hanes
Journal: Journal of Clinical Oncology (2016)

9095 Background: ABP 215 is a biosimilar candidate highly similar to BEV, a VEGF inhibitor, in analytical and functional comparisons. Pharmacokinetic similarity between ABP 215 and BEV has been demonstrated in a phase 1 study. Here we present primary efficacy and safety results from a phase 3 study in non-small cell lung cancer (NSCLC). Methods: In this double-blind, active-controlled trial, subjects with non-squamous NSCLC on first-line chemotherapy with carboplatin and paclitaxel were randomized (1:1) to ABP 215 or BEV (15 mg/kg IV infusion Q3W for 6 cycles). Patients (Pts) remained on treatment until 21 days after the last dose of investigational product (IP) or study specified chemotherapy. Clinical equivalence of the primary endpoint was evaluated by comparing the 2-sided 90% confidence interval (CI) of the risk ratio (RR) of objective response rate (ORR) between study arms with the prespecified margin (0.67, 1.5). Results: Baseline characteristics were balanced between groups (ABP 215: n = 328; BEV: n = 314). ORR (ITT population) was 39.0% (n = 128) for ABP 215 and 41.7% (n = 131) for BEV; the RR for ORR was 0.93 (90% CI: 0.80, 1.09). Pts with grade ≥ 3 treatment-emergent adverse events (TEAEs) were 42.9% in ABP 215 group vs 44.3% in BEV group; TEAEs leading to IP discontinuation affected 18.8% and 17.2% subjects in the two groups. Pts reporting at least one serious TEAE were 26.2% in ABP 215 group vs 23.0% in BEV group. TEAEs with > 10% incidence included alopecia, nausea, neutropenia, peripheral neuropathy, and hypertension. Patients developing binding antibodies were 1.4% in the ABP 215 group vs 2.5% in the BEV group; no subject tested positive for neutralizing antibodies. Conclusions: The study met its primary endpoint demonstrating that ABP 215 is clinically similar to BEV. TEAEs were comparable between ABP 215 and BEV. Clinical trial information: NCT01966003.
The EpSSG NRSTS 2005 treatment protocol for desmoid-type fibromatosis in children: an international prospective case series
Authors: Daniel Orbach, Bernadette Brennan, Gianni Bisogno, Max Van Noesel, Véronique Minard-Colin, Julia Daragjati, Michela Casanova, Nadege Corradini, Ilaria Zanetti, Gian Luca De Salvo, Anne Sophie Defachelles, Anna Kelsey, Myriam Ben Arush, Nadine Francotte, Andrea Ferrari
Journal: The Lancet Child & Adolescent Health (2017)
FRI0306 Long term drug-free remission is feasible in severe behcet's disease after cessation of successful anti-tnf treatment: a single center, retrospective longitudinal outcome study
Authors: PP Sfikakis, A Arida, S Panopoulos, K Fragiadaki, G Pentazos, A Laskari, M Tektonidou, N Markomichelakis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The efficacy of anti-TNF treatment for patients with severe forms of Behcet9s disease (BD) is well established (ref), but long term data on the outcome after cessation of such treatment are lacking. <h3>Objectives</h3> To examine whether sustained long term remission of severe BD is feasible after cessation of successful anti-TNF treatment. <h3>Methods</h3> This retrospective longitudinal outcome study was conducted in December 2016 and included all patients with severe BD refractory to conventional immunosuppressive therapy who were considered complete responders to continuous anti-TNF treatment in our center, the first being treated in 2000. Study9s endpoint was the proportion of patients achieving sustained complete remission of BD for at least 3 years after cessation of the anti-TNF agent. <h3>Results</h3> A total of 28 patients in whom infliximab and/or adalimumab treatment was given, always combined with azathioprine unless not tolerated (n=2), and discontinued anytime before December 2013 were eligible for analysis. Following cessation of successful anti-TNF treatment (median duration of 2 years) 13/28 patients achieved the study9s end-point. The main reason for anti-TNF administration was sight-threatening ocular disease (n=12) or intestinal disease (n=1). The remaining 15 patients relapsed within 1.5 year (main reason for anti-TNF: ocular disease, n=9; neuro-BD, n=2; severe mucocutaneous disease, n=3; intestinal disease, n=1; median treatment duration of 24 months); 12/15 were successfully re-treated with anti-TNF. So far, 3 of them (ocular disease, n=2; neuro-BD, n=1) have achieved the study9s end-point (median re-treatment duration of 2 years). Overall, our 16 patients who achieved the study9s end-point (57%) are in complete disease remission ranging from 3 to 12 years (5.7 years, median). Nine patients with severe ocular disease are currently any drug-free (32%), whereas the 7 remaining patients are on low doses of conventional immunosuppressive therapy (25%). Notably, those patients on drug-free remission had shorter median disease duration at initiation of anti-TNF treatment, compared to the remaining patients (1 versus 3 years, respectively). <h3>Conclusions</h3> Sustained drug-free remission for many years after cessation of successful anti-TNF treatment is feasible in some patients with severe BD. Since anti-TNF-induced "cure" can never be differentiated from a spontaneous remission by natural history, further studies should examine whether early anti-TNF treatment must be intended for every patient with severe BD. <h3>References</h3> Hatemi G, et al. EULAR recommendations for the management of Behçet disease. Ann Rheum Dis. 2008 Dec;67(12):1656–62. <h3>Disclosure of Interest</h3> None declared
Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells
Authors: Gregory A. Wasserman, Aleksander D. Szymaniak, Anne C. Hinds, Kazuko Yamamoto, Hirofumi Kamata, Nicole M.S. Smith, Kristie L. Hilliard, Claudia Carrieri, Adam T. Labadorf, Lee J. Quinton, Xingbin Ai, Xaralabos Varelas, Felicia Chen, Joseph P. Mizgerd, Alan Fine, Dónal O’Carroll, Matthew R. Jones
Journal: Journal of Clinical Investigation (2017)

P-element-induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells. Isolation and next-generation sequencing of MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells. Mice lacking MIWI2 exhibited an altered balance of airway epithelial cells, demonstrating fewer multiciliated cells and an increase in club cells. During pneumococcal pneumonia, Miwi2-deficient mice exhibited increased expression of inflammatory mediators and increased immune cell recruitment, leading to enhanced bacterial clearance. Taken together, our data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. By demonstrating roles for MIWI2 in airway cell identity and pulmonary innate immunity, these studies elucidate unanticipated physiological functions for Piwi proteins in somatic tissues.
Annals Story Slam - Becoming Batman
Authors: Nilay Shah
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - Becoming BatmanFREENilay Shah, MDNilay Shah, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0057 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Becoming Batman "Becoming Batman," by Dr. Nilay Shah (Duration 06:42)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Nilay Shah, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, [email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...