tbuckley/cabot-search huggingface dataset:
FRI0041 INCIDENCE AND TREND OF PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) IN PATIENTS WITH RHEUMATOID ARTHRITIS IN SPAIN. (TREND-AR STUDY)
Authors: María Espinosa, Alberto García-Vadillo, Carmen Barbadillo, Natalia Crespí-Villarías, Manuel Fernandez-Prada, María Galindo-Izquierdo, Hilda Godoy, Angeles Herranz Varela, Cristina Macía-Villa, Concepción Morado Quiroga, Jose Luis Morell Hita, Marina Peña, Elia Perez-Fernandez, Javier Quirós, Virginia Villaverde, Cristina Martinez-Prada, Ramón Mazzucchelli
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Treatment with biological agents is recognized as a potential risk factor for the development of Progressive Multifocal Leukoencephalopathy (PML), a rare and often fatal demyelinating disease of the CNS caused by John Cunningham Virus infection. <h3>Objectives</h3> Analyze the incidence and trend of hospital admissions for PML in patients with RA, in Spain, during the period between 1999 and 2015. <h3>Methods</h3> Population study based on the analysis of a national administrative database that includes a Minimum Basic Data Set (MBDS) of the income of patients with RA (ICD 9 714). Period: January 1, 1999, to December 31, 2015. The cases of PML were identified due to the presence in the primary and secondary diagnosis of the codes ICD 9 046.0 to 046.9. The population at risk was estimated through the population census of the National Institute of Statistics, with an estimated prevalence of RA of 0.5% in both sexes (0.2% in men and 0.8% in women). Crude and adjusted rates were calculated at national level. The trend was analyzed using Generalized Linear Models (MLG) using the variable year as the analysis variable. <h3>Results</h3> Of the total of 338,343 hospital admissions in patients with RA during the 17 years of the study period, only 14 cases (0.004%) of PML were recorded, nine (64.3%) were women and 5 (35.7%) men. The mean age was 69.5 years (SD 16.8); 74.56 (SD14.8) in women and 60 (SD18.1) in men (p = 0.145). Five patients (35.7%) died during admission (2 women and 3 men) (p = 0.266). The average of the Charlson index was 2.21 (SD 1.7); 3 (SD 2.5) in women and 1.78 (SD 1.1) in men (p = 0.227). The crude incidence rate of PML was 0.54/100,000 inhabitants * year, 0.85/100,000 inhabitants * year in men and 0.37/100,000 inhabitants * year in women. The Relative Risk male: female was 2.34. The gross rate of PML increased from 0.32/105 * year in the period 1999-2002, to 0.74 between 2011 and 2015, both in women (from 0.19 in the period 1999-2002 to 0.52 from 2011 to 2015) as well as men (from 0.82 in the period 1999-2002 to 1.64 during 2011-2015). It is estimated that this increase is of 19.7% per year. <h3>Conclusion</h3> In Spain, between 1999 and 2015, there has been an increase in the incidence rate of PML in patients with RA. We estimate an annual increase of 19,7%. <h3> Disclosure of Interests: </h3> None declared
PS1275 INVASIVE ASPERGILLOSIS CAUSED BY ”RARE“ PATHOGENS: CLINICAL REGISTRY DATA ANALYSIS
Authors: O. Shadrivova, I. Ryabinin, E. Desyatik, Y. Borzova, A. Volkova, M. Popova, T. Bogomolova, L. Zubarovskaya, B. Afanasyev, N. Vasilyeva, N. Klimko
Journal: HemaSphere (2019)

Background: Publications describing invasive aspergillosis (IA) caused by “rare” pathogens are limited. Species identification of the pathogen is necessary for the selection of antifungal therapy, as some Aspergillus spp. may be resistant to antifungal drugs. Aims: Analysis clinical registry data of patients with IA caused by “rare” pathogens Methods: Retrospective analysis of patients with IA caused by “rare” pathogens in 1998–2019 yy. For the IA diagnosis EORTC / MSD, 2008 criteria were used. In accordance with the European guidelines, DNA sequencing and MALDI‐TOF were used to identify of the “rare” Aspergillus spp. Results: In our registry we included 800 patients with IA. In 227 patients Aspergillus spp. were isolated. The “rare” pathogens were detected in 18 (8%), and these patients were included in group I; age varied from 5 to 67 years, median – 40.5,males – 50%. The control group consisted 209 patients with other Aspergillus spp. ( A. fumigatus,A. niger and A. flavus ), from 1 to 99 years old, median ‐ 47, males – 53%. In both groups IA predominantly occurs in patients with hematologic malignancies (73% vs 76%): acute leukemia – 27% vs 33%, lymphoma – 22% vs 27%, multiple myeloma 12% vs 6%, chronic leukemia 6% in each group, other hematological diseases – 6% vs 4%. We identified, IA caused by ”rare“ pathogens more often developed in children(22% vs 11%, p &lt; 0.05). In addition to standard risk factors, in patients with ”rare“ pathogens more often was detected lymphocytopenia 67% vs 55%, with duration 21 vs 14 days, p &lt; 0.05, less frequent was noted fever (46% vs 78%, p &lt; 0.05), but significantly more lung damage accompanied by hemoptysis (17% vs 10%, p &lt; 0.05). “Rare” pathogens were A. ustus – 38% , A. nidulans – 22% , A. calidoustus – 8%, A. versicolor – 8%, A.glaucus – 8%, A. candidus – 8%, and A. sydowii – 8%. In controlgroup etiological agents were A. fumigatus – 52% ,A. niger – 31%, A. flavus– 17%. Two or more species of Aspergillu s were isolated in 44% vs 9%, p &lt; 0.05. Antifungal therapy was used in 100% vs 97% of patients. Twelve weeks overall survival rate was 82% vs 81%. In the group with “rare” pathogens more frequently observed relapse of IA – 33% vs 12%, p &lt;0.05. Summary/Conclusion: Patients with “rare” pathogens account for 8% of patients with isolated Aspergillus spp. cultures. IA caused by ”rare“ pathogens, more often occurs in children – 22%. The features of IA caused by “rare” pathogens are: long‐term lymphocytopenia (67%, median ‐ 21 days), combination of two or more pathogens – 44%, high relapse rate – 33%. Survival of patients with “rare” pathogens does not differ from the total cohort of patients – 82%.
Abstract 15161: Angiotensin Ii Receptors and Nadph Oxidase Mediate Angiotensin Ii Stimulation Of Neuronal Nitric Oxide Synthase Protein Expression and Activity in Murine Left Ventricular Myocardium
Authors: Ji Hyun Jang, Chun Zi Jin, Sung Joon Kim, Yin Hua Zhang
Journal: Circulation (2012)

Nitric oxide (NO) deficiency is responsible for increased oxidative stress and myocardial pathogenesis. Convincing evidence has shown that the protein expression and activity of neuronal nitric oxi...
Abstract 16511: Discoidin Domain Receptor-1: A Novel Molecular Switch Regulating Fibrocalcific Response in Vascular Smooth Muscle Cells
Authors: Jona B Krohn, Joshua D Hutcheson, Eduardo Martinez-Martinez, Carlijn Bouten, Michelle P Bendeck, Elena Aikawa
Journal: Circulation (2015)

Background: Extracellular vesicle (EV)-derived microcalcifications formed in collagen-poor fibrous caps contribute to plaque rupture. Collagen accumulation and calcification are major determinants of plaque stability, although the mechanisms linking fibrotic and calcific responses are unknown. The collagen receptor discoidin domain receptor-1 (DDR-1) regulates plaque calcification in vivo ; however, its role in the release of calcifying EVs remains unclear. We hypothesize that DDR-1 regulates the processes of fibrosis and EV-induced calcification in atherosclerotic plaques. Methods and results: Smooth muscle cells (SMC) from the carotid arteries of wild type and DDR-1 knockout (DDR-1 -/- ) mice (n=5 per group) were cultured in control or calcifying media. At days 14 and 21, cells were harvested and EVs isolated for analysis. Compared to wild type cells, DDR-1 -/- SMCs exhibited a 3.5-fold increase in EV release (p&lt;0.001) as well as elevated EV calcifying potential determined by EV-bound alkaline phosphatase (ALP) activity (470.4±30.0 vs. 19.1±2.3 ng/well/mg protein). DDR-1 -/- SMCs showed an increase in ALP activity (220.3±31.2 vs. 6.9±1.2 ng/well/mg protein), calcification measured by alizarin red S absorbance (3.56±0.11 vs. 0.10±0.0008), and collagen type I accumulation (p=0.04). Transforming growth factor-β (TGFβ) signaling has been implicated in both fibrotic and calcific responses. DDR-1 -/- cells released significantly more TGFβ in calcifying medium (253.4±12.4 vs. 167.2±8.8 pg/ml, p&lt;0.001), suggesting a connection between DDR-1 and TGFβ signaling. A selective TGFβ receptor I inhibitor mitigated the osteogenic potential of the DDR-1 -/- phenotype with a significant decrease in EV release, ALP activity in SMCs and EVs, extracellular matrix calcification and collagen production. Analysis of TGFβ-associated pathways in DDR-1 -/- SMCs revealed significantly increased p38 phosphorylation while phosphorylated Smad3 and JNK were inhibited. Conclusion: DDR-1 interferes with TGFβ-mediated p38 phosphorylation to restrict EV-induced calcification. DDR-1 concomitantly attenuates collagen accumulation in vascular SMCs, establishing a novel mechanism of cell-matrix interaction in arterial fibrocalcific responses.
PB2258 ERYTHROPOIESIS STIMULATING AGENTS (ESAS) IN MANAGEMENT OF MYELODYSPLASTIC SYNDROMES: RECAMDS TRIAL
Authors: C. Cerchione, G. Martinelli, I. Soriente, A. M. D’Arco, P. Danise, G. Cerciello, F. Pane, F. Alfinito
Journal: HemaSphere (2019)

Background: Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low‐risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Aims: Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion‐dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. Methods: 183 patients, treated with standard‐dose ESAs, have been retrospectively analyzed (Table 1). Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R‐IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1‐118). Results: Overall response rate (ORR) was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non‐responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic‐responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic‐responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion‐dependence, regarded as first signs of progression of disease. Non‐responders were 30/183 (16.3%): in the macrocytic non‐responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic. Summary/Conclusion: These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses.
Germline Pathogenic Variants in 7636 Japanese Patients With Prostate Cancer and 12 366 Controls
Authors: Yukihide Momozawa, Yusuke Iwasaki, Makoto Hirata, Xiaoxi Liu, Yoichiro Kamatani, Atsushi Takahashi, Kokichi Sugano, Teruhiko Yoshida, Yoshinori Murakami, Koichi Matsuda, Hidewaki Nakagawa, Amanda B Spurdle, Michiaki Kubo
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Genetic testing has been conducted in patients with prostate cancer (PCa) using multigene panels, but no centralized guidelines for genetic testing exist. To overcome this limitation, we investigated the demographic and clinical characteristics of patients with pathogenic variants. Methods We sequenced eight genes associated with hereditary PCa in 7636 unselected Japanese patients with PCa and 12 366 male, cancer-free control individuals. We assigned clinical significance for all 1456 variants using the American College of Medical Genetics and Genomics guidelines and ClinVar. We compared the frequency of carriers bearing pathogenic variants between cases and control participants with calculated PCa risk in each gene and documented the demographic and clinical characteristics of patients bearing pathogenic variants. All statistical tests were two-sided. Results We identified 136 pathogenic variants, and 2.9% of patients and 0.8% of control individuals had a pathogenic variant. Association with PCa risk was statistically significant for variants in BRCA2 (P &amp;lt; .001, odds ratio [OR] = 5.65, 95% confidence interval [CI] = 3.55 to 9.32), HOXB13 (P &amp;lt; .001, OR = 4.73, 95% CI = 2.84 to 8.19), and ATM (P &amp;lt; .001, OR = 2.86, 95% CI = 1.63 to 5.15). We detected recurrent new pathogenic variants such as p.Gly132Glu of HOXB13. Patients with pathogenic variants were 2.0 years younger at diagnosis and more often had smoking and alcohol drinking histories as well as family histories of breast, pancreatic, lung, and liver cancers. Conclusions This largest sequencing study of PCa heredity provides additional evidence supporting the latest consensus among clinicians for developing genetic testing guidelines for PCa.
Abstract 15210: Differential Phosphorylation of Members of the Mitogen Activated Protein Kinase and Apoptosis Pathways in Response to Ischemic Preconditioning in Rat Myocardium
Authors: Kiersten A Liddy, Melanie Y White, Benjamin L Parker, Nestor Solis, Brett D Hambly, Stuart J Cordwell
Journal: Circulation (2012)

Despite being first described 26 years ago, the protective mechanisms of ischemic preconditioning (IPC) are still largely unknown. A response to conditioning stimuli is rapidly mounted, and thus ph...
SAT0452 VITAMIN D INSUFFICIENCY AND DEFICIENCY ARE ASSOCIATED WITH A HIGHER LEVEL OF SERUM URIC ACID: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nipith Charoenngam, Ben Ponvilawan, Patompong Ungprasert
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Several studies have revealed a relationship between vitamin D status and a number of non-skeletal health conditions such as insulin resistance, metabolic syndrome, cardiovascular diseases, inflammatory diseases, infection and malignancy. The interaction between serum uric acid and vitamin D has also been observed. A study found that uric acid can suppress 1-alpha-hydroxylase in vitro and in vivo, leading to the reduction in the conversion of the storage form of 25-hydroxyvitamin D into the active form of 1,25-dihydroxyvitamin D [1]. In fact, several epidemiological studies have suggested that patients with vitamin D insufficiency and deficiency tend to have a higher level of serum uric acid compared to those with adequate vitamin D level although the results were inconsistent across the studies. <h3>Objectives:</h3> To compare serum uric level between individuals with normal vitamin D level versus patients with vitamin D deficiency and vitamin D insufficiency. <h3>Methods:</h3> A systematic review was conducted using MEDLINE and EMBASE database from inception to October 2018 to identify all studies that compared the level of serum uric acid between individuals with normal vitamin D level and patients with vitamin D insufficiency/deficiency. Eligible studies must be cohort or cross-sectional studies that consisted of two groups of adult participants, one with normal level of vitamin D (vitamin D level &gt;30 ng/ml) and one with vitamin D insufficiency (vitamin D level 20-30 ng/ml) or vitamin D deficiency (vitamin D level of &lt;20 ng/ml). Mean serum uric acid level and standard deviation of participants in each group were extracted from each study to calculate mean difference (MD) between the groups. Pooled MD was then calculated by combining MDs of each study using random-effects model. <h3>Results:</h3> A total of seven cross-sectional studies were eligible for the meta-analyses. Individuals with normal vitamin D level had a significantly lower serum uric acid level than patients with vitamin D insufficiency with the pooled MD of -0.33 mg/dL (95% CI, -0.61, -0.04) (figure 1) and also had a significantly lower serum uric acid level than patients with vitamin D deficiency with the pooled MD of -0.45 mg/dL (95% CI, -0.82, -0.08) (figure 2). The statistical heterogeneity was high with the I<sup>2</sup> of 78% and 89%, respectively. Funnel plots of both meta-analyses were fairly symmetric which did not suggest the presence of publication bias. <h3>Conclusion:</h3> Both patients with vitamin D insufficiency and patients with vitamin D deficiency had a significantly higher level of serum uric acid compared to individuals with normal vitamin D level. <h3>References</h3> [1] Chen W, et al. (2014) Uric acid suppresses 1 alpha hydroxylase in vitro and in vivo. Metabolism. 63, 150-60. <h3>Disclosure of Interests:</h3> None declared
PB2029 HEPATITIS B REACTIVATION DURING TREATMENT OF TYROSINE KINASE INHIBITORS—EXPERIENCE IN 175 ADULT PATIENTS WITH CHRONIC MYELOID LEUKEMIA
Authors: Y.‐H. Wang, J.‐D. Liang, W.‐H. Sheng, F.‐M. Tien, C.‐Y. Chen, J.‐L. Tang, H.‐F. Tien
Journal: HemaSphere (2019)

Background: The cause of hepatitis B virus (HBV) reactivation in patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) is unclear. Aims: Taiwan has a high prevalence of HBV infection, and this study aimed to investigate the epidemiology of HBV reactivation in patients with CML treated with TKIs. Methods: We retrospectively reviewed 175 adult patients with CML who were treated using TKIs at National Taiwan University Hospital between January 2008 and July 2018. HBV infection status and reactivation were reviewed during follow‐up. Results: A total of 99 men and 76 women with a median age of 46 years (range: 18–97) were enrolled in this study. Twenty‐one (12%) of 175 patients were carrying HBV when they were diagnosed with CML. Eight HBV carriers were prophylactically treated using an antiviral agent, and the others were closely followed‐up. At a median follow‐up period of 41 months (range 1–129 months), 6 (28.6%) of the 21 HBV carriers had 7 episodes of HBV reactivation. Two (1.3%) of the 154 negative hepatitis B surface antigen (HBsAg) patients had reverse seroconversion and became positive HBsAg, and both patients had acute blastic transformation and allogeneic transplantation. A univariate analysis revealed positive HBsAg and negative anti‐Hepatitis B surface antibodies (anti‐HBs Ab) significantly correlated with HBV reactivation. In this retrospective cohort study, the incidence of HBV reactivation was 0.5 per 100 person‐years in patients with CML carrying HBV who had been treated with TKIs and 0.076 per 100 person‐years in all patients with CML treated with TKIs. Summary/Conclusion: HBV reactivation could develop in patients with CML treated with TKI, especially in those who are HBV carriers. The incidence is lower than it is in hematological patients with HBV carrier status who have been treated with chemotherapy, immunotherapy and stem cell transplantation. We suggest that all patients with CML with positive HBsAg undergo prophylaxis with an antiviral agent. The cause of HBV reactivation in patients with resolved HBV infection and no allogeneic transplantation is unclear, and although the risk is low, further investigation is required. image
FRI0317 NOVEL CLASSIFICATION OF IDIOPATHIC INFLAMMATORYMYOPATHIES BASED ON DISTINCTIVE FEATURES AND AUTOANTIBODIES: ANALYSIS OF 67 KOREAN PATIENTS
Authors: Sang Wan Chung, In Seol Yoo, Su-Jin Yoo, Jinhyun Kim, Seong Wook Kang, Seungcheol Shim, Mihye Kwon, Chung-Il Joung, Seung-Jae Hong, Yeon-Ah Lee
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> SinceBohan and Peter first described their diagnostic criteria foridiopathic inflammatorymyopathies (IIM) in 1975, new discoveries suchas myositis-specific and myositis-associated autoantibodies (Abs) have been made. <h3>Objectives</h3> To investigate correlations between specificmyositis Abs and their frequenciesand clinical associationsacross different IIM groups, collectively demonstrating theutility of the new clinicoserologic classification in Koreanadult patients with IIM. <h3>Methods</h3> We conducted a multicenter cohort study including 67adult patients (age≥18 years) who have been diagnosed as IIM by ENMC criteria.Immunoblot assay with Euroline strip(EUROIMMUN, Germany)was performed using the sera of definite deramatomyositis (DM, n=36), definite polymyositis (PM, n=25), amyopathic DM (n=4), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (IMNM, n=1). Patients were classifiedbased on three classifications: 1) novel clinicoserologic classification suggested by Troyanov et al. in 2017. 2) 2017 EULAR/ACR classification criteria. 3) 2004 European neuromuscular center (ENMC) criteria.Associations ofmyositis Absand clinical subsets of IIM were investigated. <h3>Results</h3> The distribution of the various IIM differed strikingly from those using the 3 classifications (Fig1). According to the 2004 ENMC classification and 2017 EULAR/ACR classification criteria, DM and PM was the most and the second frequent entities (DM: 55.2%, 56.7%; PM: 35.8%, 37.3%). But, using the new clinicoserologic classification,overlapmyositis(OM) is the major type of IIM and the frequency of PM is significantly decreased.Anti-ARS Abs specificity included anti-Jo-1(16.4%), -OJ(4.6%), -EJ(6.2%) -PL-7(3.1%), and -PL-12(4.6%). Interstitial lung disease was closely associated with anti-MDA5,and anti-ARS Abs, while DM-specific skin lesion was frequently observed in patients with anti-TIF1γ and anti-ARS Abs. Sevenpatients with cancer-associated DM were identified. They were positive for anti-TIFγ (5/7) and anti- SRP(3/7) (table 1). <h3>Conclusion</h3> Novel classification based on distinctive features and new myositis Absreflects the clinical phenotype of IIM better. Establishment of a system routinely available to screen myositis Abs is needed. Thiswill be beneficial to providemore precise diagnosis and proper management for patients with IIM. <h3>Reference:</h3> [1] Jean-Luc Senecal, Jean-Pierre Raynauld, Yves Troyanov. A New Classification of Adult Autoimmune Myositis. Arthritis Rheum2017;69:878-884. <h3>Disclosure of Interests</h3> None declared