tbuckley/cabot-search huggingface dataset:
FRI0030 Synovial mast cells identify patients with a severe phenotype in a cohort of dmard naÏve patients with early rheumatoid arthritis
Authors: F Rivellese, F Humby, A Nerviani, S Pagani, D Mauro, A de Paulis, G Marone, C Pitzalis
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Mast cells (MCs) are among the immune cells participating to the inflammatory response in Rheumatoid Arthritis (RA), but their exact contribution to disease development and progression is unclear. <h3>Objectives</h3> To evaluate the presence of MCs in the synovia of patients with early RA naïve to treatment and their correlation with baseline clinical phenotype, response to DMARDs and disease progression. <h3>Methods</h3> DMARD-naïve patients with early (&lt;12 months) RA (n=99) fulfilling the 2010 ACR/EULAR criteria were recruited as part of the Pathobiology of Early Arthritis Cohort at Barts Health NHS Trust. Sections of paraffin embedded synovial tissue obtained by ultrasound-guided synovial biopsy were stained by immunohistochemistry for CD117 (c-kit) and patients were classified into MC+ and MC- groups. Differences in clinical parameters at baseline and 6 months and progression in radiographic damage at 12 months were evaluated. The expression of Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL) by human primary MCs was assessed by western blot and immunofluorescence. <h3>Results</h3> The presence of synovial CD117+ MCs was significantly associated with highly active disease (DAS28, ESR, CRP, tender and swollen joint counts, p&lt;0.05). At the 6 months follow-up, there were no differences in terms of response to treatment with synthetic DMARDs (e.g. DAS28 remission 38.8% in MC+ vs 42.9% in MC-, p=0.725). Nonetheless, MC+ patients showed a significantly higher prevalence of radiographic progression at 12 months (progressors/non progressors 13/38 in MC+ vs 0/28 in MC-, p=0.003, n=79). When progressors were compared with non progressors, there were no differences in clinical parameters at baseline (inflammatory markers, DAS28, ACPA or RF positivity). Because of the observed association of MCs with radiographic progression, we looked for mechanisms that could link MCs to bone erosions, and we found that human primary MCs express the osteoclast activator RANKL. <h3>Conclusions</h3> We show that synovial MCs identify patients with a severe clinical phenotype in a DMARD-naïve early RA cohort. In particular, despite a similar rate of response to DMARDs at 6 months, the presence of synovial MCs at baseline was significantly associated with radiographic progression at 12 months. As clinical parameters at baseline showed no association with radiographic progression, our work suggests that the analysis of synovial MCs could help to identify patients at high risk of progression in radiographic damage, warranting further investigations to confirm the association of MCs with the development of joint damage and their direct contribution to bone erosion, possibly via a RANKL-mediated activation of osteoclasts. <h3>Disclosure of Interest</h3> None declared
Unrelated matched versus autologous transplantation in adult patients with good and intermediate risk acute myelogenous leukemia in first molecular remission
Authors: Norbert‐Claude Gorin, Myriam Labopin, Thomas Pabst, Peter Remenyi, Depei Wu, Anne Huynh, Liisa Volin, Jean Yves Cahn, Ibrahim Yakoub‐Agha, Melanie Mercier, Mohamed Houhou, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2017)

Patients with Acute Myelogenous Leukemia have a better outcome if reaching molecular remission. We compared the outcome of 373 patients autografted and 335 patients allografted with a 10/10 compatible unrelated donor in first molecular remission. Patients were stratified using the ELN European Leukemia Net classification. ELN favorable group: (234 auto and 70 unrelated transplants). By univariate analysis, in the auto group, the Non Relapse Mortality (NRM) was lower (3.7% versus 19%; P < 10-4 ), Relapse Incidence (RI) higher (29% versus 17%, P < 10-4 ), Leukemia Free Survival (LFS) identical (67% versus 64%) and Overall Survival (OS) better than in the allogeneic group (83% versus 62%; P = .008). By multivariate analysis, autologous transplantation was associated with a lower NRM (HR: 4, P = .01) and a better OS (HR: 2.08, P = .04). ELN intermediate group 1: (87 autologous and 172 unrelated transplants). By univariate analysis, in the auto group, NRM was lower (2.5% versus 11.8%; P = .03), RI higher (59% versus 18%, P < 10-6 ), LFS lower (39% versus 70%; P < 10-6 ) and OS lower than in the unrelated donor group (61% versus 74%; P = .005). By multivariate analysis, unrelated donor was superior to autologous transplantation for LFS (HR: 0.36, P < 10-5) and OS (HR: 0.53, P = .01). ELN intermediate group 2: (52 autologous and 93 unrelated donors). The outcome was identical. We conclude that good risk patients get higher benefit from autologous transplantation. Intermediate risk 2 patients have the same outcome and Intermediate risk 1 patients get higher benefit from unrelated donor transplants.
OP0038 Myositis autoantibodies outperform clinical subgroup classification in predicting muscle weakness in myositis patients
Authors: I Pinal-Fernandez, W Huang, M Casal-Dominguez, E Tiniakou, C Parks, K Pak, J Albayda, JJ Paik, SK Danoff, L Christopher-Stine, AL Mammen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Myositis patients may be classified as belonging to one of four clinical groups: dermatomyositis (DM), polymyositis (PM), clinically amyopathic dermatomyositis (CADM) or necrotizing myositis (NM). Alternatively, myositis patients may be classified according to myositis autoantibody status. <h3>Objectives</h3> The aim of this study was to determine whether clinical groups or myositis autoantibodies provide better prognostic categories with regard to muscle involvement in these patients. <h3>Methods</h3> All Johns Hopkins Myositis Center patients from 2002 to 2015 with a myositis specific autoantibody confirmed by two different immunologic techniques were included. Autoantibody groups accounting for less than 2% of the final sample size were excluded. Strength (analyzed as the average of deltoid and hip flexor strength using Kendall9s scale) and log transformed CK levels were compared between the different autoantibody groups using multilevel regression models adjusted for age, time from disease onset, sex, race and treatments. Models with different combinations of key variables were compared using the likelihood ratio test to ascertain if autoantibody groups and clinical subgroups provided the same amount of information regarding muscle weakness and CK levels over time. <h3>Results</h3> 483 patients with 4181 visits were included and 10 different autoantibody groups were identified. Muscle weakness and CK levels followed a gradient among both antibody and clinical groups. Anti-SRP patients had the greatest weakness, followed by anti-HMGCR, anti-Mi2 and anti-NXP2, and then anti-Jo1. CK levels were highest in anti-HMGCR patients, followed by anti-SRP, anti-PL7, anti-Jo1 and anti-Mi2. Interestingly, strength and CK levels were dissociated in two groups: anti-NXP2 patients had significant weakness with low CK levels and anti-PL7 patients were relatively strong despite high CK levels. Multilevel regression models showed autoantibody groups explained the strength and the CK variability better than the clinical groups (AIC difference&gt;20). Indeed, adding clinical groups to a model using only autoantibodies did not improve the model9s ability to predict strength (p=0.2) and only mildly improved its ability to predict CK (p=0.01). In comparison, adding the autoantibodies to a model using the clinical groups resulted in a marked improvement in predicting both CK and strength (both p&lt;0.001). <h3>Conclusions</h3> In patients with myositis, autoantibody status predicts strength and CK levels better than clinical grouping. <h3>Disclosure of Interest</h3> None declared
PAZOTHYR: A randomized, multicenter, open-label, phase II study of the optimal scheme of pazopanib in radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC).
Authors: Christelle De La Fouchardiere, Dalac Audrey, Yann Godbert, Stephane Bardet, Vincent Rohmer, Fieffe Sandrine, Sophie Leboulleux, Martin Schlumberger, Alain Ravaud, Christine Do Cao, Stéphane Vignot, Damien Pouessel, Claire Cropet, Florent Quiblier, Julien Gautier, David Pérol
Journal: Journal of Clinical Oncology (2014)

TPS6106 Background: Patients with locally advanced/metastatic progressive RAIR-DTC usually have a poor prognosis and may receive tyrosine kinase inhibitors (TKI) as first line therapy. Pazopanib (P) emerged as a promising alternative in a phase II study, with high Objective Response Rates (ORR) (49%; n=18/37) and prolonged Progression-Free Survival (PFS) (mPFS = 11.7 months) (Bible et al. Lancet Oncol. 2010). However, as with other tyrosine kinase inhibitors, the toxicity profile of P leads physicians to consider dose modifications (dose reductions, temporary and/or permanent discontinuation) that may jeopardize the clinical outcome. In addition, the probability of severe toxicity and the difficulty for patients to tolerate mild to moderate events increases with the treatment duration. We decided to investigate an alternative scheme of P preserving clinical benefits for patients and their well-being. Methods: A randomized, multicenter, open-label phase II study is ongoing in French patients with advanced RAIR-DTC to identify the optimal treatment strategy, through a new approach. After a 6-month period of continuous P treatment following inclusion, patients with controlled disease (CR, PR or SD) are randomized between a standard strategy (daily P maintained until disease progression (PD) or unacceptable toxicity) and an experimental sequential scheme in which P is temporarily stopped every 6 cycles, and reintroduced as soon as the patient experience PD (RECIST 1.1). This sequential scheme is followed until a PD occurs under P. The primary objective of the study is to compare the two arms in terms of Time to Treatment Failure, defined as the time from randomization to permanent discontinuation of treatment due to any cause. Secondary endpoints of the study include ORR and duration of response, disease control rate, PFS and overall survival. Quality of Life Questionnaire C30 will provide precious complementary data on the potential impact of the proposed strategy on patients’ quality of daily living. To date, 13 of the planned 168 patients have been enrolled and 2 patients have been randomized. Clinical trial information: NCT01813136.
SP0004 Peptidyl arginine deiminase 4 and rheumatoid arthritis: from human genetics to murine models
Authors: K Yamamoto
Journal: Annals of the Rheumatic Diseases (2017)

We have previously reported that functional haplotypes of peptidyl arginine deiminase 4 <i>(PADI4</i>) are associated with rheumatoid arthritis (RA). We found that transcripts of the risk haplotype of <i>PADI4</i> are more stable than those of the non-risk haplotypes, suggesting that increased expression and function of PAD4 (encoded by <i>PADI4</i> gene) increase the risk of RA. The association has been confirmed by several studies with different ethnics. Further, we also reported <i>PADI4</i> polymorphisms highly predispose male smokers to RA. Since PAD4 catalyzes an arginine residue in a protein to citrulline and anti-citrullinated protein antibodies (ACPA) are highly specific in RA, it has been reasonable to speculate that increased PAD4 is associated with increased citrullinated proteins, leading to the initiations of tolerance breakdown or inflammatory arthritis. However, the mechanisms of PAD4 involvement turned out to be more complex than previously thought in animal models. In order to investigate the pathological process in detail, we made <i>Padi4</i> knockout mice. Decreased severity of experimental autoimmune arthritis wad observed in these mice. Further, we found PAD4 regulates the pro-apoptotic fate of neutrophils, and promotes the expression of pro-inflammatory cytokines in macrophages. These actions could result in the pro-arthritic roles of <i>PADI4</i>. Recently, neutrophil extracellular traps (NETs) were reported as an important immune stimulator in RA and SLE, and PADI4 is required for the generation of NETs. Especially, NET-containing immune complex (IC) stimulated plasmacytoid dendritic cells to accelerate the interferon secretion in SLE. Therefore, <i>PADI4</i> could play several different roles in the immune system and also in the pathogenesis of autoimmune diseases. <h3>Disclosure of Interest</h3> None declared
The impact of skin hyperpigmentation and hyperchromia on quality of life: A cross-sectional study
Authors: Mayra B.C. Maymone, Hind H. Neamah, Stephen A. Wirya, Nicole M. Patzelt, Eric A. Secemsky, Pedro Q. Zancanaro, Neelam A. Vashi
Journal: Journal of the American Academy of Dermatology (2017)
The Mortality and Myocardial Effects of Antidepressants Are Moderated by Preexisting Cardiovascular Disease: A Meta-Analysis
Authors: Marta M. Maslej, Benjamin M. Bolker, Marley J. Russell, Keifer Eaton, Zachary Durisko, Steven D. Hollon, G. Marie Swanson, J. Anderson Thomson Jr., Benoit H. Mulsant, Paul W. Andrews
Journal: Psychotherapy and Psychosomatics (2017)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Antidepressants (ADs) are commonly prescribed medications, but their long-term health effects are debated. ADs disrupt multiple adaptive processes regulated by evolutionarily ancient biochemicals, potentially increasing mortality. However, many ADs also have anticlotting properties that can be efficacious in treating cardiovascular disease. We conducted a meta-analysis assessing the effects of ADs on all-cause mortality and cardiovascular events in general-population and cardiovascular-patient samples. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Two reviewers independently assessed articles from PubMed, EMBASE, and Google Scholar for AD-related mortality controlling for depression and other comorbidities. From these articles, we extracted information about cardiovascular events, cardiovascular risk status, and AD class. We conducted mixed-effect meta-analyses testing sample type and AD class as moderators of all-cause mortality and new cardiovascular events. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Seventeen studies met our search criteria. Sample type consistently moderated health risks. In general-population samples, AD use increased the risks of mortality (HR = 1.33, 95% CI: 1.14-1.55) and new cardiovascular events (HR = 1.14, 95% CI: 1.08-1.21). In cardiovascular patients, AD use did not significantly affect risks. AD class also moderated mortality, but the serotonin reuptake inhibitors were not significantly different from tricyclic ADs (TCAs) (HR = 1.10, 95% CI: 0.93-1.31, &lt;i&gt;p&lt;/i&gt; = 0.27). Only “other ADs” were differentiable from TCAs (HR = 1.35, 95% CI: 1.08-1.69). Mortality risk estimates increased when we analyzed the subset of studies controlling for premedication depression, suggesting the absence of confounding by indication. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The results support the hypothesis that ADs are harmful in the general population but less harmful in cardiovascular patients.
SAT0303 Clinical differences between definite and probable antiphospholipid (APS) patients: should they be treated the same?
Authors: F Signorelli, G Balbi, RA Levy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The management of patients with recurrent thromboses/pregnancy morbidity and transient detection of antiphospholipids antibodies (aPL) can be a medical challenge. Although these patients are commonly seen in practice, there are no specific guidelines for the treatment in this situations. <h3>Objectives</h3> To investigate the clinical differences between definite and probable APS patients. <h3>Methods</h3> We performed a cross-sectional study in a group of 90 outpatients seen in our department. Seventy-seven of them met the Sydney classficiation criteria for definte APS, and thirteen had thrombosis or gestational morbidity, but no definite serological criteria for the diagnosis of APS. Clinical and serological features were collected during visits and by chart review, and the two groups were compared. Transient aPL was defined as only one detection of aPL (lupus anticoagulant, anticardiolipin IgM/IgG and/or anti-beta-2-glycoprotein 1 IgM/IgG) after 2 or more assays, at least 12 weeks apart. <h3>Results</h3> Demographic and clinical characteristics are shown in Table 1. In a bivariate analysis, there was no difference between groups regarding the criteria and non-criteria manifestations of APS, except for the presence of livedo (p=0.033). In a multivariate regression analysis, the model was adjusted to age, sex, and variables with p&lt;0.10 in the bivariate analysis (age, sex, race, livedo, Raynaud9s phenomenon). No difference between groups was found after the analysis. <h3>Conclusions</h3> This study suggests patients with transient detection of aPL have the same clinical characteristics of patients with definite APS, including thrombotic features, pregnancy morbidity, and non-criteria manifestations. In this context, our data suggests that both groups should be treated according to the current treatment guidelines for APS. <h3>Disclosure of Interest</h3> None declared
Thawed and Washed Apheresis Products Keep an Excellent CD34+ Cells Viability for 24 Hours Using Either Voluven or Normal Saline Plus Albumin
Authors: Miguel Blanquer Blanquer, Carmen Alguero, Pilar Menchon, Assumpta Ferrer, Pilar Martínez Avilés, Ana García Hernandez, Francisca Iniesta, Jose Maria Moraleda
Journal: Blood (2016)
C/EBP homologous protein–induced loss of intestinal epithelial stemness contributes to bile duct ligation–induced cholestatic liver injury in mice
Authors: Runping Liu, Xiaojiaoyang Li, Zhiming Huang, Derrick Zhao, Bhagyalaxmi Sukka Ganesh, Guanhua Lai, William M. Pandak, Phillip B Hylemon, Jasmohan S. Bajaj, Arun J. Sanyal, Huiping Zhou
Journal: Hepatology (2017)

Impaired intestinal barrier function promotes the progression of various liver diseases, including cholestatic liver diseases. The close association of primary sclerosing cholangitis (PSC) with inflammatory bowel disease highlights the importance of the gut‐liver axis. It has been reported that bile duct ligation (BDL)‐induced liver fibrosis is significantly reduced in C/EBP homologous protein knockout (CHOP −/− ) mice. However, the underlying mechanisms remain unclear. In the current study, we demonstrate that BDL induces striking and acute hepatic endoplasmic reticulum (ER) stress responses after 1 day, which return to normal after 3 days. No significant hepatocyte apoptosis is detected 7‐14 days following BDL. However, the inflammatory response is significantly increased after 7 days, which is similar to what we found in human PSC liver samples. BDL‐induced loss of stemness in intestinal stem cells (ISCs), disruption of intestinal barrier function, bacterial translocation, activation of hepatic inflammation, M2 macrophage polarization and liver fibrosis are significantly reduced in CHOP −/− mice. In addition, intestinal organoids derived from CHOP −/− mice contain more and longer crypt structures than those from wild‐type (WT) mice, which is consistent with the upregulation of stem cell markers (leucine‐rich repeat‐containing G‐protein‐coupled receptor 5, olfactomedin 4, and SRY [sex determining region Y]‐box 9) and in vivo findings that CHOP −/− mice have longer villi and crypts as compared to WT mice. Similarly, mRNA levels of CD14, interleukin‐1β, tumor necrosis factor‐alpha, and monocyte chemotactic protein‐1 are increased and stem cell proliferation is suppressed in the duodenum of patients with cirrhosis. Conclusion: Activation of ER stress and subsequent loss of stemness of ISCs plays a critical role in BDL‐induced systemic inflammation and cholestatic liver injury. Modulation of the ER stress response represents a potential therapeutic strategy for cholestatic liver diseases as well as other inflammatory diseases. (H epatology 2018;67:1441‐1457).
AB0222 The serum anti-citrullinated protein/peptide antibodies in children with juvenile idiopathic arthritis
Authors: H Zeng
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objectives</h3> To investigate the diagnostic value and prognostic usefulness of anti-citrullinated protein/peptide antibodies (ACPA) in children with juvenile idiopathic arthritis (JIA). <h3>Methods</h3> The presence of ACPAs in the serum samples from 81 JIA patients were determined using Anti-CCP IgG, CCCP3.1 IgG and IgA ELISA. Citrullinated Protein Antibodies, Anti-MCV, and Aeskulisa RA/CP-Detect which coated various citrullinated antigen substrates: synthetic cyclic peptide, recombinant rat filaggrin, mutated human vimentin, and IgG-derived peptides. 55 children with other joint diseases and 49 healthy donors were control groups. The diagnostic performance of ACPAs was analyzed and correlations between ACPAs and radiological damage were evaluated. <h3>Results</h3> CPAs in 8.8–28.4% of JIA group were detected with specificity of 84.6–98.1%. ACPAs could be seen in all subtypes of JIA, and high levels of ACPAs were particularly found in the RF positive JIA patients No healthy control had increased ACPA tested for CCP, CCP3.1, and CPA, whilst 3and 2 of healthy controls were found positive to MCV and RA/CP, respectively. The presence of ACPAs correlated more frequently with the presence of RF (P&lt;0.05). The ACPA positivities in 18 JIA patients with radiological damage were 27.8–55.6%, which higher than that in patients without damage, and of the ACPA (CCP, CCP3.1, CPA, or MCV) positive JIA patients, 62.5%, 62.5%, 52.9%, 43.5% respectively had radiological damage, which significantly higher than that in JIA patients without ACPA (P&lt;0.05). <h3>Conclusions</h3> This study confirms the main presence of ACPAs in children with polyarticular JIA, especially those with RF positive using ELISA based methods, and ACPAs relate significantly with joint erosions in JIA. <h3>Disclosure of Interest</h3> None declared
Restrictive Cardiomyopathy
Authors: Eli Muchtar, Lori A. Blauwet, Morie A. Gertz
Journal: Circulation Research (2017)

Restrictive cardiomyopathy (RCM) is characterized by nondilated left or right ventricle with diastolic dysfunction. The restrictive cardiomyopathies are a heterogenous group of myocardial diseases that vary according to pathogenesis, clinical presentation, diagnostic evaluation and criteria, treatment, and prognosis. In this review, an overview of RCMs will be presented followed by a detailed discussion on 3 major causes of RCM, for which tailored interventions are available: cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis. Each of these 3 RCMs is challenging to diagnose, and recognition of each disease entity is frequently delayed. Clinical clues to promote recognition of cardiac amyloidosis, cardiac sarcoidosis, and cardiac hemochromatosis and imaging techniques used to facilitate diagnosis are discussed. Disease-specific therapies are reviewed. Early recognition remains a key barrier to improving survival in all RCMs.