tbuckley/cabot-search huggingface dataset:
SAT0237 MYOCARDIAL FDG-PET/CT FINDINGS IN CHILDREN WITH TAKAYASU ARTERITIS
Authors: Kenichi Nishimura, Seira Hattori, Ayako Murase, Ai Ohnishi, Ryoki Hara, Shuichi Ito
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Takayasu arteritis (TAK) is a chronic large-vessel vasculitis affecting the aorta and its major branches<sup>1)</sup>. In Japan, <sup>18</sup>F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) was approved since April 2018. Recently, usefulness of FDG-PET/CT to diagnose TAK or assess disease activity has been reported<sup>2)</sup>. However, the findings in children with TAK except for vascular lesions remain unknown. <h3>Objectives:</h3> We aimed to retrospectively analyse the FDG-PET/CT findings in children with TAK except for vascular lesions. <h3>Methods:</h3> This is a single-center retrospective observational study. We evaluated 9 children with TAK and compared them with 10 children with other rheumatic disease (systemic juvenile idiopathic arthritis; 5, polyarticular juvenile idiopathic arthritis; 1, juvenile dermatomyositis; 1, Crohn's disease; 2, Kikuchi's disease; 1) (control group). All children underwent FDG-PET/CT before the treatment. We compared the two groups for the age at performed FDG-PET/CT, sex, duration of onset to performed FDG-PET/CT, FDG-PET/CT findings. Binary data were analyzed by Fisher's exact test. <h3>Results:</h3> Median age of the performed FDG-PET/CT was 13.9 (range; 11.1-14.9) years old in TAK children and 5.4 (1.4-12.4) years old in control group. Both groups include 6 females. Median duration of onset to performed FDG-PET/CT was 1 (range; 0-12) months in TAK children and 0 (0-12) months in control group. FDG accumulation in bone marrow was observed in 7 TAK patients (78%) and in 7 (70%) of control group. Moreover, FDG accumulation in spleen was observed in 7 TAK patients (78%) and in 10 (100%) of control group. These findings were common in both groups. On the other hand, FDG accumulation in left ventricular myocardium was observed in 8 TAK patients (89%) but in 3 (30%) of control group (p=0.02). Six TAK children received follow-up FDG-PET/CT. Myocardium FDG accumulation was continued in 3 children but resolved in 2. TAK children with persistent accumulation in myocardium had ascending aorta dilation later. <h3>Conclusion:</h3> FDG accumulation in left ventricular myocardium would be a characteristic finding in children with TAK, and possibly related to later ascending aorta dilation. <h3>References</h3> [1] Jennette JC, Falk RJ, Bacon PA, et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum 2013; 65: 1-11 [2] Danve A, O'Dell J. The Role of 18F Fluorodeoxyglucose Positron Emission Tomography Scanning in the Diagnosis and Management of Systemic Vasculitis. Int J Rheum Dis 2015; 18: 714-24 <h3>Disclosure of Interests:</h3> None declared
Abstract P061: Perfluoroalkyl Acids and Stroke Risk in Persons with and without Diabetes: A Salutatory Effect of High Oxygen Carrying Capacity Environmental Contaminants
Authors: Baqiyyah Conway, Tina Costacou
Journal: Circulation (2016)

Background: Perfluroakly acids (PFAAs) are persistent environmental contaminants linked to certain adverse health outcomes; however, their association with macrovascular diseases has been equivocal. PFAAs are also potent oxygen transporters used in organ preservation and synthetic blood development. Little information is available on the relationship of PFAAs with risk of stroke, for which ischemia in the brain blood vessels is a major cause. Persons with diabetes are at 2-to-9-fold increased risk of stroke, largely due to an increased risk of ischemic stroke. We thus tested the association of four common PFAAs with stroke, and whether this varied by diabetes status. Methods: Participants were drawn from the C8 Health Project (n=5,270 and 48,832 w/ and w/out diabetes, respectively, age≥20 ys), which collected blood samples, self-reported demographics, medical diagnoses, height, and weight in 2005-2006 as part of a legal settlement following perfluorooctanoate (PFOA) contamination of drinking water in West Virginia and Ohio. Four PFAAs were assessed separately: PFOA, perfluorononaoic acid (PFNA), perfluorohexane sulfonate (PFHxS), and perfluoroctane sulfonate (PFOS). Estimated glomerular filtration rate (eGFR) was assessed via the MDRD formula. Results: There were 344 (6.5%) stroke cases among those with diabetes and 731 (1.5%) among those without diabetes. Adjusting for age, sex, and eGFR, higher concentrations of each of the PFAAs were associated with a lower likelihood of stroke (OR for PFOA=0.93, 0.88-0.97; OR for PFNA=0.83, 0.74-0.94; OR for PFOS=0.83, 0.77-0.90; OR for PFHxS=0.82, 0.76-0.89). Effect modification by diabetes status was observed for the sulfonate PFAAs (p-interaction &lt;0.001 each). In those with diabetes, higher concentrations of PFOS were associated with a significantly greater reduction in the likelihood of stroke (OR=0.76, 0.69-0.87) than the risk reduction in those without diabetes (OR=0.93, 0.84-1.04). For PFHxS, higher serum concentrations were associated with 31% lower likelihood of stroke in persons with diabetes (OR=0.69, 0.61-0.79) but only a 3% lower likelihood in persons without diabetes (OR=9=0.97, 0.88-1.07). No such effect modification by diabetes status was observed for PFOA or PFNA (p-interaction&gt;0.30 each). Conclusion: PFAAs are inversely related to stroke risk. This relationship appears to be stronger in persons with diabetes, perhaps due to the salutary effect of the high oxygen carrying capacity of these substances and the longer half- life of PFAA sulfonates in human proteins than the non-sufonate containing PFAAs.
Abstract 18035: Diastolic Pulmonary Gradient in Risk Stratifying Pre-Heart Transplant Pulmonary Hypertension
Authors: Marjan Mujib, Rayan Yousefzai, Matthew Jankowich, Nishant Shah, Alan Morrison, Sartaj Gill, Wen-Chih Wu, Gaurav Choudhary
Journal: Circulation (2017)

Background: Pulmonary vascular resistance (PVR) is used as a surrogate of pulmonary vascular remodeling and risk-predictor of post-transplant outcomes when selecting heart transplant (HT) candidate...
Exploring the genetic basis of human population differences in DNA methylation and their causal impact on immune gene regulation
Authors: Lucas T. Husquin, Maxime Rotival, Maud Fagny, Hélène Quach, Nora Zidane, Lisa M. McEwen, Julia L. MacIsaac, Michael S. Kobor, Hugues Aschard, Etienne Patin, Lluis Quintana-Murci
Journal: Genome biology (2018)

DNA methylation is influenced by both environmental and genetic factors and is increasingly thought to affect variation in complex traits and diseases. Yet, the extent of ancestry-related differences in DNA methylation, their genetic determinants, and their respective causal impact on immune gene regulation remain elusive. We report extensive population differences in DNA methylation between 156 individuals of African and European descent, detected in primary monocytes that are used as a model of a major innate immunity cell type. Most of these differences (~ 70%) are driven by DNA sequence variants nearby CpG sites, which account for ~ 60% of the variance in DNA methylation. We also identify several master regulators of DNA methylation variation in trans, including a regulatory hub nearby the transcription factor-encoding CTCF gene, which contributes markedly to ancestry-related differences in DNA methylation. Furthermore, we establish that variation in DNA methylation is associated with varying gene expression levels following mostly, but not exclusively, a canonical model of negative associations, particularly in enhancer regions. Specifically, we find that DNA methylation highly correlates with transcriptional activity of 811 and 230 genes, at the basal state and upon immune stimulation, respectively. Finally, using a Bayesian approach, we estimate causal mediation effects of DNA methylation on gene expression in ~ 20% of the studied cases, indicating that DNA methylation can play an active role in immune gene regulation. Using a system-level approach, our study reveals substantial ancestry-related differences in DNA methylation and provides evidence for their causal impact on immune gene regulation.
AB1407-HPR NEUROLOGICAL MANIFESTATIONS DURING THE BEHCET DISEASE
Authors: Skouri Wafa, sameh sayhi, Najah Boussetta, Rim Dhahri, Faida Ajili, Louzir Bassem
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> behcet disease MB is a systemic inflammatory disease whose common histopathological substratum is a vasculitis that can reach all vessels. Neurological impairment is one of the diagnostic criteria for MB. A serious condition affects the functional and vital prognosis. <h3>Objectives</h3> The aim of our work was to study the epidemiological, clinical, therapeutic and evolutionary characteristics of patients with BD with neurological involvement. <h3>Methods</h3> This was a retrospective, monocentric, descriptive study of NB from the adult population collected from a population of 150 patients monitored for MB. The study was conducted in the Neurology and Internal Medicine departments over a period of 19 years, from January 1997 to December 2015. Patients meeting the criteria of the international Study Group of the MB of 1990, those of the criteria of the International Criteria for Behcet Disease (ICBD) and the diagnostic criteria of Neuro-behcet defined proposed by the international consensus of experts of 2014. <h3>Results</h3> We collect 35 patients. The gender ration was at 6 with 30 men for 5 women. The mean age of our population was 34+- 1.92 years. The neurological manifestations had inaugurated the MB in 55% of the cases. Ninety-four percent of patients had central nervous system involvement, while two patients had peripheral polyradiculoneuritis. Central involvement was parenchymal in 85% of cases, nonparenchymatous in 3% of cases and lixed in 6% of cases. Cerebral imaging showed predominant demyelinating lesions in periventricular and brain stem in 15 patients, a peudo-tumor appearance in 3 patients, and vascular lesions with arterial aneurysm and cerebral thrombophlebitis in 2 patients. Therapeutically, all patients received corticosteroid therapy with immunosuppressive therapy for 15 patients. Three patients had received an immunomodulatory treatment of anti-TNF a Type. The evolution was by push in 60% of cases, primary progressive in 20% of cases and secondarily progressive in the rest of the cases. Three-quarters of patients with parenchymal brain injury had a favorable outcome. The Outcome was unfavorable in all patients with diffuse disease, brain stem damage, spinal cord injury, angio-behavior, polyradiculoneuropathy and mixed impairment. The change in visual impairment (NORB) was favorable in one case in two. <h3>Conclusion</h3> Neurological manifestations of MB are serious complications, and are typically poor prognosis both on a vital and functional level. Mortality remains high and neurological sequelae (motor and neuropsychological) are heavy. The prognosis in all the worse because the treatment is instituted late, hence the interest of an early and well conducted treatment <h3>Disclosure of Interests</h3> None declared
Chemotherapeutic Dose Scheduling Based on Tumor Growth Rates Provides a Case for Low-Dose Metronomic High-Entropy Therapies
Authors: Jeffrey West, Paul K. Newton
Journal: Cancer Research (2017)

We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted MTD strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction. This advantage was magnified for fast-growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this article agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low-volume tumors. Cancer Res; 77(23); 6717-28. ©2017 AACR.
THU0610 ANALYSIS OF ANTINUCLEAR ANTIBODY ANTIBODIES POSITIVITY AND THEIR MAJOR KARYOTYPES IN PATIENTS WITH AUTOIMMUNE DISEASES AND HEALTHY SUBJECTS
Authors: Qiujing Wei, Yutong Jiang, Jiewen Xie, Jun Qi, Jieruo Gu
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Autoantibodies, especially antinuclear antibodies (ANA), play an important role in the diagnosis and differential diagnosis of autoimmune disease (AID), disease monitoring, efficacy observation and pathogenesis research. <h3>Objectives</h3> Our aim was to investigate the rate of ANA positivity and their major karyotypes in different AIDs and healthy controls. <h3>Methods</h3> The distribution and positive rate of Antinuclear antibody (ANA) karyotypes detected by indirect immunofluorescence in 3704 patients with AID and 1073 healthy subjects were retrospectively analyzed. <h3>Results</h3> The positive rate of ANA in different AID groups was 90.7% (1845/2034) in SLE, 54% (525/973) in RA, 86.4% (267/309) in SS, 90.3% (140/155) in pSS, 92.3% (36/39) in MCTD, 93.4% (128/137) in PBC and 49.1% (28/57) in the AIH group. The positive rate of ANA in the health subjects was 11.5% (123/1073), see Figure 1. Totally, the positive rate of ANA in the AID group was 80.1% (2967/3704). The karyotypes were detected as homogeneous type (15.8% (586/3704)), nuclear particle type (49.7% (1840/3704)), cytoplasmic particle type (5.3% (196/3704)), mixed type (2.8% (91/3704)) which was mainly composed of nuclear membrane/cytoplasmic granules, more common in PBC. See Table 1. The karyotype of ANA in the health group was mainly homozygous (7.0% (75/1073)). Figure 1 ANA positive rate in difference AID patients and healthy subjects <h3>Conclusion</h3> There are differences in ANA positive rates among patients with different AIDs. Some mixed karyotype analyses may provide important evidence for the diagnosis of PBC and AIH. Healthy subjects can have partial ANA positivity which is predominantly homogenous. <h3>Disclosure of Interests</h3> None declared
SAT0431 RED GINSENG EXTRACTS SUPPRESS MONOSODIUM URATE CRYSTAL INDUCED NLRP3 ACTIVATION
Authors: Jennifer Lee, Moon Young Kim, Sung-Hwan Park
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> It is well known that red ginseng extracts (RGE) has anti-inflammatory properties. <h3>Objectives</h3> We aimed to investigate if RGE could suppress monosodium urate crystal (MSU) - induced NLRP3 activation and thus could be a potential therapeutic for gout. <h3>Methods</h3> Acute air-pouch model was used to investigate <i>in vivo</i> effect on acute gouty inflammation of RGE in mice. Human monocyte cell line –THP-1- was stimulated with MSU in the presence of RGE and expression of NLRP3, ASC, caspase-1, IL-1β was measured by PCR, immunoblotting and ELISA. Twenty four gout patients in intercritical period were randomized either to red ginseng tablet or placebo receiving group in a double-blind manner. After 3months of taking red ginseng tablets (RGT)/placebo, expression of NLRP3 and inflammatory cytokines of peripheral blood mononuclear cell was addressed by PCR. <h3>Results</h3> RGE sufficiently inhibited acute gouty inflammation in air-pouch mouse model, represented by reduced number of white blood cells in air pouch lavage fluid. <i>In vitro</i>, RGE dose-dependently suppressed MSU-induced IL-1 β production of THP-1 cells. RGE did not affect NLRP3 or pro IL-1 β expression. However, ASC oligomerization was inhibited and suppreseed NLRP3 inflammasome assembly. Patients taking RGT for 3 months showed significantly reduced NLRP3 expression compared to baseline, which was not observed in the control group. <h3>Conclusion</h3> RGE successfully suppressed MSU-induced acute inflammation in mouse model. Also, RGT reduced NLRP3 expression in intercritical gout patients. These results suggest that red ginseng can be implicated as a therapeutic agent for gout. <h3>References</h3> [1] Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440(7081):237-41. [2] 2 Kingsbury SR, Conaghan PG, McDermott MF. The role of the NLRP3 inflammasome in gout. Journal of inflammation research. 2011;4:39-49. <h3>Disclosure of Interests</h3> None declared
AB0662 UTILITY OF NAILFOLD CAPILLAROSCOPY FOR THE EARLY DIAGNOSIS OF SYSTEMIC SCLEROSIS SPECTRUM OF DISEASES IN ASIA
Authors: Cassandra Hong, Andrea Low
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The utility of nailfold capillaroscopy (NFC) has largely been evaluated in patients with Raynaud's Phenomenon (RP). However, in equatorial countries, RP occurs in only 79% (1) and 84% (2) of patients in Singapore and Malaysia respectively. In the early stages of Systemic Sclerosis (SSc), patients may develop autoantibodies or puffy fingers before the onset of RP (3). <h3>Objectives</h3> There is no data on the utility of NFC in patients with non-RP features suggestive of the scleroderma-spectrum of diseases (SSc, mixed connective tissues disease, dermatomyositis). We aim to compare the utility of NFC for the early diagnosis of the SSc-spectrum of diseases in patients who present with and without RP. <h3>Methods</h3> Patients referred to our institution for NFC evaluation from March 2010 – March 2017 were recruited. Patients with confirmed diagnosis of a connective tissue disease were excluded. Eligible patients were divided into 4 groups: (I) RP with or without positive aNA; (II) Undifferentiated non-RP features to suggest SSc-spectrum diseases and negative aNA; (III) Undifferentiated non-RP features to suggest SSc-spectrum diseases and positive aNA &gt;1/400 and (IV) Positive SSc-associated autoantibodies without features to suggest SSc-spectrum diseases. Images were analysed at 200x magnification using a software analysis program. Patients were noted to have normal, aspecific or SSc pattern on NFC, defined by the presence of &gt;1 giant capillary, avascular areas or &gt;2 dilated capillaries with areas of hemorrhage. <h3>Results</h3> 133 patients were recruited (mean age 55 years, 87% female; 76% Chinese, 7% Malay, 10% indian, 7% other ethnicity). ANA was positive in 74 (82.2%) patients (n=25 anti-centromere, n=3 anti-Scl70). Taking into consideration NFC patterns, the clinical outcomes were normal in 32 patients (35.6%), connective tissue disease (CTD) suspected in 33 patients (36.7%), and definite CTD in 25 patients (27.8%). Diagnostic yield for SSc-spectrum of diseases was highest in Groups I and III (Table 1). <h3>Conclusion</h3> In patients without RP, NFC was most useful to confirm a diagnosis in those with undifferentiated features to suggest SSc-spectrum of diseases and positive aNA. <h3>References</h3> [1] Santosa a, Tan C, Teng G, et al. Lung and gastrointestinal complications are leading causes of death in SCORE, a multi-ethnic Singapore systemic sclerosis cohort. Scand J Rheumatol2016Nov;45(6):499-506. [2] Pagalavan L, ong S. Demography, clinical and laboratory features of systemic sclerosis in a Malaysian rheumatology centre. Med J Malaysia. 2007Jun;62(2):117-21. [3] Englert H, Champion D, Wu J, et al. Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'. Intern Med J. 2011Feb;41(2):197-9. <h3>Disclosure of interests</h3> None declared
AB1418-HPR MOBILE-PHONE-BASED HOME EXERCISE TRAINING PROGRAM IN PATIENTS WITH KNEE OSTEOARTHRITIS
Authors: Onur Aydogdu, Uhud Sevinç, Zübeyir Sarı
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Most rehabilitation programs are hospital-based and rely on regular supervision (1). However, mobile health technologies such as smartphone applications may provide lower-cost ways to monitor and train the patients (2). We have developed a mobile-phone application for monitoring and training the patients at home. <h3>Objectives</h3> The purpose of this study was to compare a mobile-phone-based home exercise training program along with supervised physiotherapy program to a brochure-based home exercise training program along with supervised physiotherapy program in patients with knee osteoarthritis. We hypothesized that the patients who received mobile-phone-based home exercise training program along with supervised physiotherapy program over 3 weeks would have better balance, quality of life and less pain and disability score versus the patients who received brochure-based home exercise training program along with supervised physiotherapy program. <h3>Methods</h3> This was a randomized, prospective, comparative clinical study. The study included 40 patients, aged 4565 years, who diagnosed with a grade 2-3 knee osteoarthritis. The patients were randomly divided into two groups. While one group (n=20) received a mobile-phone-based home exercise training program along with supervised physiotherapy program, the second group (n=20) received a brochure-based home exercise training program along with supervised physiotherapy program as 15 sessions for a total of three weeks, five sessions per week. Pain intensity, balance, disability, and quality of life were measured with Visual Analogue Scale, Berg Balance Scale, WOMAC, and SF-36, respectively. All of the assessments procedures were performed again after the treatment. <h3>Results</h3> There were statistically significant improvements in measures of pain intensity, balance, disability, and quality of life between pre- and post treatment in both groups (p&lt;0.05). However, no significant differences were found in any of patient outcome variables between the groups (p&gt;0.05). <h3>Conclusion</h3> We could report that mobile-phone-based home exercise training program is not superior to brochure-based home exercise training program in terms of patient outcomes over 3-week program. <h3>References</h3> [1] Wang CH, Chou PC, Joa WC, et al. Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study. BMC Pulm Med. 2014Aug30;14:142. [2] Persell SD, Karmali KN, Stein N, et al. Design of a randomized controlled trial comparing a mobile phone-based hypertension health coaching application to home blood pressure monitoring alone: The Smart Hypertension Control Study. Contemp Clin Trials. 2018Oct;73:92-97. <h3>Disclosure of Interests</h3> None declared