tbuckley/cabot-search huggingface dataset:
Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis
Authors: Milica Vukmirovic, Xiting Yan, Kevin F. Gibson, Mridu Gulati, Jonas C. Schupp, Giuseppe DeIuliis, Taylor S. Adams, Buqu Hu, Antun Mihaljinec, Tony N. Woolard, Heather Lynn, Nkiruka Emeagwali, Erica L. Herzog, Edward S. Chen, Alison Morris, Joseph K. Leader, Yingze Zhang, Joe G.N. Garcia, Lisa A. Maier, Ronald G. Collman, Wonder P. Drake, Michael J. Becich, Harry Hochheiser, Steven R. Wisniewski, Panayiotis V. Benos, David R. Moller, Antje Prasse, Laura L. Koth, Naftali Kaminski
Journal: European Respiratory Journal (2021)

Background Sarcoidosis is a multisystem granulomatous disease of unknown origin with a variable and often unpredictable course and pattern of organ involvement. In this study we sought to identify specific bronchoalveolar lavage (BAL) cell gene expression patterns indicative of distinct disease phenotypic traits. Methods RNA sequencing by Ion Torrent Proton was performed on BAL cells obtained from 215 well-characterised patients with pulmonary sarcoidosis enrolled in the multicentre Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study. Weighted gene co-expression network analysis and nonparametric statistics were used to analyse genome-wide BAL transcriptome. Validation of results was performed using a microarray expression dataset of an independent sarcoidosis cohort (Freiburg, Germany; n=50). Results Our supervised analysis found associations between distinct transcriptional programmes and major pulmonary phenotypic manifestations of sarcoidosis including T-helper type 1 (Th1) and Th17 pathways associated with hilar lymphadenopathy, transforming growth factor-β1 (TGFB1) and mechanistic target of rapamycin (MTOR) signalling with parenchymal involvement, and interleukin (IL)-7 and IL-2 with airway involvement. Our unsupervised analysis revealed gene modules that uncovered four potential sarcoidosis endotypes including hilar lymphadenopathy with increased acute T-cell immune response; extraocular organ involvement with PI3K activation pathways; chronic and multiorgan disease with increased immune response pathways; and multiorgan involvement, with increased IL-1 and IL-18 immune and inflammatory responses. We validated the occurrence of these endotypes using gene expression, pulmonary function tests and cell differentials from Freiburg. Conclusion Taken together, our results identify BAL gene expression programmes that characterise major pulmonary sarcoidosis phenotypes and suggest the presence of distinct disease molecular endotypes.
POS0997 PERFORMANCE OF ASDAS VERSUS BASDAI DURING PREGNANCY
Authors: P. Fischer, A. Zbinden, F. Foerger
Journal: Annals of the Rheumatic Diseases (2021)

Background: Disease activity in patients with axial spondyloarthritis (axSpA) can be measured by BASDAI and ASDAS. Both instruments were validated in non-pregnant patients with cutoff values for active diseases. In pregnant women with axSpA, however, BASDAI and ASDAS scores might be biased by signs and symptoms of pregnancy itself. Objectives: To compare the performance of ASDAS and BASDAI during pregnancy Methods: Patients with axSpA were prospectively followed before pregnancy, at each trimester and 6 to 12 weeks postpartum. Disease activity was assessed by BASDAI, ASDAS, patient global assessment (PGA) and physician global assessment (PhGA). We analysed the disease course throughout pregnancy and postpartum, the correlation between BASDAI and ASDAS and the agreement in the classification of active disease. We applied receiver operating curves (ROC) to evaluate the cut-off points in pregnant patients. Results: The study involved 40 women with axSpA. Disease activity scores were higher during pregnancy (median ASDAS score: 2.5, median BASDAI score 3.1) than during a non-pregnant state (median ASDAS score 2.3, median BASDAI score 2.1). Median BASDAI scores were highest at the first trimester, median ASDAS scores were highest at the second trimester. ASDAS strongly correlated with BASDAI, both in the pregnant and in the non-pregnant state (r=0.796, r=0.727). However, there was a discordance when analysing the proportion of patients with high disease activity using the common cut-off values (ASDAS &gt;2.1, BASDAS &gt;4). More patients had high disease activity when measured by ASDAS (1 st trimester (T): 63%, 2 nd T: 76%, 3 rd T: 61%) compared to those measured by BASDAI (1 st T 43%, 2 nd T: 39%, 3 rd T: 34%). The κ coefficient showed only fair agreement (κ=0.39). ROC analysis among pregnant patients showed that the cut-off point estimation for high disease activity using ASDAS &gt;2.75 corresponded to a BASDAI &gt;4. The ASDAS &gt;2.75 cut-off for high disease activity had a good agreement with BASDAI &gt;4 (κ=0.657). When ASDAS &gt;2.75 was applied in pregnant women with axSpA, about 40% experienced high disease activity. Conclusion: During pregnancy, the majority of women with axSpA experience ongoing disease activity. However, the cut-off values defining low and high disease activity might differ between pregnant and non-pregnant individuals since BASDAI and ASDAS are biased by pregnancy related symptoms like fatigue and mechanical back pain. Disclosure of Interests: None declared.
POS0559 SPECKLE TRACKING BETTER DETECTS SUBCLINICAL MYOCARDIAL DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: I. Kirillova, T. Popkova, Y. Gorbunova, A. Volkov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2021)

Background: The risk of developing cardiovascular complications and death in rheumatoid arthritis (RA) is 50% higher than in the total population. These clinical events depend from risk factors for cardiovascular diseases, chronic inflammation and inflammatory myocardial infiltration. А new method for detecting early myocardial dysfunction is echocardiography using speckle tracking echocardiography. Objectives: to determine the frequency of myocardial dysfunction (lower global longitudinal epicardial strain of left ventrical (LV), diastolic dysfunction of left ventricle (LVDD)) using standard and novel echocardiographic methods in patients (pts) with RA prior to therapy with bDMARDs, examine its relationship with markers of inflammation. Methods: a total of 28 pts with a valid diagnosis of RA (ACR/EULAR, 2010): 23 f (82%) /5 m (18%) were included, median (Me) age - 56 [interquartile range (IR) 34;65] years, Me RA duration-14,5 [IR 7;87] months; all pts with RA demonstrated a high disease activity (Me DAS28 6.06, [IR 5,4;6,6]), seropositive for IgM RF (88%) and/or ACCP (84%) without any experience of administration of bDMARDs. The control group consisted of 10 healthy subjects, which were matched by sex and age. All pts were assessed for traditional risk factors for cardiovascular disease (ESC guidelines, 2011), echocardiography, tissue Doppler imaging, and the speckle tracking assessment of left ventricle longitudinal strain. DD was allocated according to the ESC guidelines for the diagnosis and treatment of heart failure (2018). Arterial hypertension was detected in 5 pts with RA. Results: In pts with RA LVDD was more often detected (8 (31%) vs 0%, p=0.05) than in controls. The values of E LV (0.77 [0.62;0.94] ms vs 1.25 [1.03;1.51] ms, p=0.0001) were lower than in control group. Speckle-tracking method detected lower global longitudinal epicardial strain (–16.5 [-18.9; -13.6]% vs –21.58 [-22.1;-20.4] %, p=0.0001). 17(61%) RA pts showed a decrease global longitudinal epicardial strain. There were no between-group differences in left ventricular ejection fraction, LV sizes, LV myocardial mass index in RA pts with controls. There were correlations between the global longitudinal epicardial strain and DAS28 (r=0,9, p&lt;0,02), tender joint score (r=0,6, p&lt;0,02), radiological stage (r=0,6, p&lt;0,008); the presence of systemic manifestations (r=0,5, p&lt;0,03). Conclusion: In pts with RA frequently (61%) were detected lower global longitudinal epicardial strain, which are associated with a high activity of the inflammatory process. Speckle-tracking echocardiography is better at detecting early myocardial dysfunction than tissue Doppler. Disclosure of Interests: None declared
POS0850 NAILFOLD CAPILLARY DILATIONS IN RAYNAUD’S PHENOMENON: QUANTIFYING A PREDICTIVE THRESHOLD FOR THE ‘SCLERODERMA PATTERN’
Authors: G. Pacini, M. Pendolino, C. Pizzorni, E. Gotelli, A. Sulli, L. Carmisciano, S. Paolino, V. Smith, M. Cutolo
Journal: Annals of the Rheumatic Diseases (2021)

Background: Non-specific abnormalities could be detected by nailfold videocapillaroscopy (NVC) in subject with primary Raynaud’s Phenomenon (RP) several years before the clinical onset of connective tissue diseases (CTD)s [1]. Previous findings from our group proved that ≤30 μm capillary dilations in RP patients have a negative predictive value for developing the ‘scleroderma pattern’ during follow-up [2]. Objectives: To investigate the role of NVC &gt;30 μm capillary dilations as positive predictive factors of the ‘scleroderma pattern’ in RP patients later developing systemic sclerosis (SSc)-related RP. Methods: A 10-year retrospective NVC-based investigation evaluated the dataset of sequential NVCs of 18 RP patients later developing SSc (cases) and 19 sex- and age-matched RP patients later developing other CTDs (controls). Both cases and controls had ≥1 NVC performed before the ‘scleroderma pattern’/CTD diagnosis (basal NVC) showing &gt;30 μm dilated capillaries. Each NVC was qualitatively and semi-quantitatively assessed, recording number of total capillaries, number and average/site-specific diameters (arterial, apical, venous) of &gt;30 μm dilated capillaries [3]. Statistical analysis was performed to stratify the risk of developing the ‘scleroderma pattern’. Results: Significant differences of capillary diameters were observed between cases and controls both at basal NVC and during follow-up (p&lt;0.001). The proportion of &gt;30 μm dilated capillaries in basal NVC was the strongest predictor of ‘scleroderma pattern’ in a median 3-year time, with a 27% cut-off (PPV 0.79, 95%CI 0.54,0.94; p&lt;0.001). Additional “Higher risk” NVC hallmarks for ‘scleroderma pattern’ development were apical diameter &gt;40 μm (p&lt;0.001), venous diameter &gt;25 µm (p&lt;0.05) and average diameter ≥35 µm (p&lt;0.005). Conversely, CTDs patients showed a stable NVC ‘non-scleroderma pattern’ over a median 10-year time. Conclusion: This is the first study to show that NVC-detected homogeneous and progressive capillary loop dilations in RP patients significantly contribute to predict the ‘scleroderma pattern’ evolution within a median 3-year time, possibly providing a “very early” window of opportunity in SSc pre-clinical stages. References: [1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15(7):753–64. [2] Trombetta AC et al. J Rheumatol 2016;43:599–606. [3] Smith et al. Autoimmun Rev 2020; 19(3):102458. Disclosure of Interests: None declared
AB0874-HPR TELEMEDICINE CONSULTING IN RHEUMATOLOGY: IDENTIFIED PROBLEMS OF NEW TECHNOLOGY
Authors: O. Teplyakova, A. Sarapulova
Journal: Annals of the Rheumatic Diseases (2021)

Background: A feature of healthcare in 2020 was the work in conditions of massive incidence of COVID-19, limited and redistribution of human resources. One of the right decisions in these conditions is to organize schools for patients, which allow simultaneous education and convey the necessary information to a large number of people. The key aspects of the organization of telemedicine schools for patients are presented. Objectives: To assess the feasibility of telemedicine schools for patients as a technology of modern health care in rheumatology. Methods: The work was carried out by the method of a one-stage cross-sectional study of the questionnaire survey of participants of education in rheumatology, conducted in an on-line mode. The number of participants in rheumatology schools was 197 people, the results of the questionnaire were received from 36 respondents. The questionnaire based on the Google platform. Results: 10 key principles of organizing online patient education at the present stage were identified: the use of distance technologies, the interest of a medical institution administration, the team approach, the technical possibilities of implementing schools, adaptation of lecture material for patients, the role of a specialized specialist in the educational process, patient participation, measurement efficiency and timely correction, development and improvement of educational technology for patients, desire for cooperation and exchange of experience. Conclusion: The emergence of new opportunities related to online health education of the population, including educational activities for patients, opens up new prospects for improving clinical care aimed at promoting health and preventing disease. Disclosure of Interests: None declared
68Ga-DOTATATE PET/CT Uptake in Prostate With an Incidental Finding of Prostatic Acinar Adenocarcinoma and Metastatic Neuroendocrine Cancer to the Liver
Authors: Muhammad Umer Nisar, Daniel N. Costa, Liwei Jia, Orhan K. Öz, Lorraine de Blanche
Journal: Clinical Nuclear Medicine (2021)

Abstract A 69-year-old man with history of metastatic neuroendocrine tumor presented for initial staging with 68 Ga-DOTATE PET/CT. 68 Ga-DOTATATE PET/CT showed incidental focal increased DOTATATE uptake in the left apical prostate tissue, which was thought to be of benign etiology. Digital rectal examination later was consistent with a palpable nodule along with elevated prostate-specific antigen of 7.0 ng/mL. MRI of prostate demonstrated a 3.8-cm lesion followed by a targeted biopsy that revealed prostatic acinar adenocarcinoma. Chronic inflammatory cell infiltrates were also noted on biopsy, and this may have been the cause of increased DOTATATE uptake seen on 68 Ga-DOTATATE PET/CT study.
Infection microenvironment-activated nanoparticles for NIR-II photoacoustic imaging-guided photothermal/chemodynamic synergistic anti-infective therapy
Authors: Nan Yang, Heng Guo, Changyu Cao, Xiaorui Wang, Xuejiao Song, Wenjun Wang, Dongliang Yang, Lei Xi, Xiaozhou Mou, Xiaochen Dong
Journal: Biomaterials (2021)
Interpretation of retrospective data evaluating high‐dose methotrexate as central nervous system prophylaxis in diffuse large B‐cell lymphoma; caution required
Authors: Nicolas Martinez‐Calle, Matthew R. Wilson, Toby A. Eyre, Kate Cwynarski, Pamela McKay, Christopher P. Fox
Journal: American Journal of Hematology (2021)

To the Editor: There remains a lack of consensus regarding the efficacy of high-dose methotrexate (HD-MTX) prophylaxis to reduce the risk of central nervous system (CNS) relapse in newly diagnosed patients with systemic diffuse large B-cell lymphoma (DLBCL). The clinical controversy reflects the lack of high-quality evidence supporting optimal prophylaxis strategies, coupled with the poor outcomes of patients who experience CNS relapse. Interest in this area has been rejuvenated recently following the publication of a number of retrospective studies1-6 investigating this critical question. We commend Puckrin and colleagues7 for attempting to address the role of HD-MTX in a retrospective evaluation of their regional practice. Although the authors acknowledge many of the limitations associated with a study of this nature, we feel that the results presented by Puckrin et al. merit a more nuanced and balanced discussion. This is particularly important when interpreting the significance of rare events, in the context of an uncontrolled modest-sized retrospective dataset exposed to a number of biases. Evaluating the effectiveness of strategies to reduce risk of CNS relapse in DLCBL is a priority area to study and, given randomized trial data may never be forthcoming, we are reliant on retrospective analyses to contribute data and generate hypotheses in this difficult area. However, it is important to be clear on the limitations of retrospective studies and to adopt appropriate caution when interpreting data generated. Based on the data and analyses presented by Puckrin et al., we believe that it is simply not possible to draw clear conclusions on the effectiveness or otherwise of HD-MTX as CNS prophylaxis. The statement included in the title of the Puckrin et al. manuscript cannot be robustly defended by the data presented. This study and other similar analyses,2, 4-6 highlight the urgent need for much larger, adequately powered, international collaborative studies of uniformly treated patients at high risk of CNS relapse in order to more confidently address this important clinical question. The authors declare no conflict of interest. Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Obesity, venous capacitance, and venous compliance in heart failure with preserved ejection fraction
Authors: Hidemi Sorimachi, Daniel Burkhoff, Frederik H. Verbrugge, Kazunori Omote, Masaru Obokata, Yogesh N.V. Reddy, Naoki Takahashi, Kenji Sunagawa, Barry A. Borlaug
Journal: European Journal of Heart Failure (2021)
Constellation of Von Hippel–Lindau Disease–Related Findings on a 68Ga-DOTATATE PET/CT
Authors: Charles Marcus, Priya Dayamani John, Monica Giles, Ila Sethi
Journal: Clinical Nuclear Medicine (2021)

Abstract Von Hippel–Lindau (VHL) is a rare predominantly hereditary syndrome characterized by multiple benign and malignant tumors that can affect different organ systems. We present representative images of a 68 Ga-DOTATATE PET/CT in a patient with confirmed VHL gene mutation, which demonstrates a constellation of findings commonly seen in these patients in one single imaging modality.
POS0246 THE WORLDWIDE INCIDENCE AND PREVALENCE OF ANCA VASCULITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF EPIDEMIOLOGICAL STUDIES
Authors: R. Redondo Rodriguez, N. Mena-Vázquez, A. M. Cabezas-Lucena, F. Godoy-Navarrete, M. Morales-Águila, S. Manrique Arija
Journal: Annals of the Rheumatic Diseases (2021)

Objectives: To evaluate the worldwide incidence and prevalence of ANCA vasculitis through a systematic review of the literature and meta-analysis. Methods: A systematic search of MEDLINE and EMBASE search engines was carried out for studies that analyzed the incidence and prevalence of ANCA vasculitis in different geographical areas . Inclusion criteria : patients diagnosed with ANCA vasculitis according to ACR criteria/ Chapel Hill Consensus and adult patients (&gt; 16 years). All ANCA vasculitis (microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis) were considered. Exclusion criteria : editorials, conference abstracts, case or cases series reports and narrative reviews; insufficient description of the methods; lack of data to compute incidence or prevalence; and duplicate studies. Variables : Main variable: the pooled prevalence measured by the number of prevalent cases per million / person-year (95% CI) and the pooled incidence measured as the number of incident cases per million / person-year (95% CI). Secondary variables : the prevalence and incidence of each vasculitis ANCA and according geographic area. A meta-analysis was undertaken to estimate the pooled incidence and the pooled prevalence per million / person-years. The 95% CI and I2 for heterogeneity were calculated. Results: Twenty four studies were included. The pooled incidence (95% CI) was 12.2 per million / person-year (8.4-16.5) and the pooled prevalence (95% CI) was 130 per million / person-year (67.5-213). The individual incidence for each vasculitis was: GPA (6.7), MPA (5.9) and EGPA (1.6). The individual prevalence for each vasculitis was: GPA (69.3), MPA (21.9) and EGPA (13.5). In the analysis by continents, the pooled incidence for GPA vasculitis was higher in Europe (7.5), while the pooled incidence for MPA vasculitis was higher in America (6.9) and for EGPA vasculitis it was higher in Asia (1.8). The pooled prevalence for GPA and MPA vasculitis was higher in Europe (83.9,24.4 respectively) than in America (14.2, 12.8 respectively). Conclusion: The pooled incidence and the pooled prevalence are higher in the case of GPA vasculitis compared to the rest of ANCA vasculitis. In general there is a predominance of incidence and prevalence of all ANCA vasculitis in the northern hemisphere compared to the south. Figure 1. The pooled incidence ANCA vasculitis. Figure 2. The pooled prevalence ANCA vasculitis Disclosure of Interests: None declared
AB0059 STUDY OF THE ANTI-INFLAMMATORY EFFECT OF CINNAMOMUM VERUM IN RATS
Authors: R. Dhouibi, A. Hanène, S. Ben Youssef, M. Ben Salem, R. Marrakchi, S. Charfi, S. Hammami, K. Ksouda
Journal: Annals of the Rheumatic Diseases (2021)

Background: Inflammatory response is a common physiological response that protects the host of many harmful stimuli such as toxins, local injuries and pathogens. Today, non-steroidal anti-inflammatory drugs are the most commonly prescribed for the treatment of many inflammatory treatments. However, long term administration of these NSAIDs causes many adverse effects, including gastrointestinal ulcers and bleeding and kidney damage. Therefore, the need for new anti-inflammatory drugs with fewer side effects is required. Objectives: The aim of our study was to evaluate the anti-inflammatory activity of Cinnamomum verum ( C. Verum ) on rats while testing the dose effect and the typical effect of the solvent. Methods: The edema was induced by injection of carrageenan solution (CARR) in paw of rats according to the method of Winter et al, 1963. The measurements of volumes of right hind paw of each rat were taken before induction of edema and each 1 h, 2 h, 3 h, 4 h and 5 h after the injection of carrageenan. 7 groups of 6 rats received, one hour before the injection of the carrageenan, different treatment: G1= witness, G2=CARR + saline solution, G3= CARR+ Acetylsalicylic acid, G4= CARR + C. verum - MeOH 100, G5= CARR + C. verum - MeOH 300, G6= CARR + CARR + C. verum - EtOH 100 and G7= CARR + C.verum - EtOH 300. Results: For this test, the volume of edema increases with time, this increase is greater in the group treated with saline solution than with the extracts of C.Verum and with Acetylsalicylic acid. The extracts of C. Verum administered intraperitoneally one hour before the injection of the carrageenan, reduced the edema in the third hour after. Conclusion: The interesting anti-inflammatory activity of Cinnamomum verum recorded in this work may at least in part support its popular use in traditional medicine [1, 2]. References: [1]Mirza Muhammad Fahd Qadir, Attya Bhatti, Muhammad Usman Ashraf, Mansur Abdullah Sandhu, Sidrah Anjum, Peter John. Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice. Inflammopharmacology 2018 Feb;26(1):157-170. [2]Heping Cao, Joseph F Urban Jr, Richard A Anderson. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr 2008 May;138(5):833-40. Disclosure of Interests: None declared