tbuckley/cabot-search huggingface dataset:
AB0045 THE RELATIONSHIP BETWEEN CD14 AND VIMENTIN-POSITIVE SYNOVIAL DENDRITIC-SHAPED CELLS AND SYNOVITIS IN RHEUMATOID ARTHRITIS
Authors: R. Kurose, T. Satoh, K. Murakami, A. Kurose, Y. I. Satoh, Y. Ishibashi, K. Ishida, K. Ogasawara, A. Morikawa, T. Sawai
Journal: Annals of the Rheumatic Diseases (2021)

Background: Inflammation in rheumatoid arthritis (RA) is caused by multiple cell types, including infiltrating inflammatory cells, such as lymphocytes, neutrophils, macrophages, and spindle-shaped fibroblasts. Especially, we are focusing on fibroblast-like synoviocytes (FLSs). In our previous study, we have reported that FLSs were positive for multiple markers including CD14, CD68 and HLA-DR, and were dendritic-shaped cells constituting nursing phenomenon between lymph or plasma cells. In addition, in our recent study, we found that CD14+FLSs were positive for vimentin (VIM), which is a marker for mesenchymal cells. There are still many issues to be discussed regarding CD14+VIM+ cells. Objectives: To investigate the relationship between CD14+VIM+ cells and the degree of synovitis in rheumatoid arthritis. Methods: Synovial tissues collected from RA patients who underwent joint surgeries were prepared for this study. First, the proportions of CD14+ cells in RA synovial tissue and control were analyzed using flow cytometry and the concentrations of inflammatory cytokines released by CD14+ cells in RA synovial tissue and control were examined by ELISA. Next, the proportions of CD14+VIM+ cells in RA synovial tissue and control were examined immunohistologically and then we analyzed the results using image analysis software. Also, we statistically analyzed the relationship between the proportion of CD14+VIM+ cells, the degree of synovitis, and clinical data. Results: Results of flow cytometry showed that CD14+ cells were frequently observed in RA synovial tissue than control. Cultured CD14+ cells released more inflammatory cytokines than cultured CD14- cells. Also, results of immunohistological staining showed that many CD14+VIM+ cells were observed in RA synovial tissue than in control. The proportion of CD14+VIM+ cells was correlated with Krenn synovitis score. High proportion cases significantly showed high level of CRP and MMP-3. Conclusion: CD14+VIM+ cells might be involved in the mechanism of chronic immunological inflammation in RA and the proportion of these cells might influence the clinical data. References: [1]Ochi T, Yoshikawa H, Toyosaki-Maeda T, Lipsky PE. Mesenchymal stromal cells. Nurse-like cells reside in thesynovial tissue and bone marrow in rheumatoid arthritis. Arthritis Research&amp;Therapy 2007; 9(1): 201. [2]Ochi T, Sawai T, Murakami K, Kamataki A, Uzuki M, Tomita T, et al. Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between the cell types. Mod Rheum 2018; 29: 1-5. [3]Krenn V, Morawietz L, Burmester GR, Kinne RW, Muller-Ladner U, Muller B, Haupl T. Synovitis score: discrimination between chronic low-grade and high-grade synovitis. Histopathology 2006; 49: 358-64. Disclosure of Interests: None declared
Abstract 416: NF-kB-Mir-23a-27a: a Critical Modulator in Post-myocardial Infarction Remodeling
Authors: Sudhiranjan Gupta, Li Li
Journal: Circulation Research (2017)

Myocardial infarction (MI) is one of the leading causes of death around the world. Myocardial ischemia contributes to the development of MI and initiates cardiomyocyte (CM) apoptosis, myofibroblasts differentiation, fibrosis and left ventricle (LV) remodeling leading to cardiac dysfunction. Previously, we have demonstrated the direct involvement of miRNAs (a new class of post-translational regulator) and NF-κB in LV remodeling. However, NF-κB-mediated miRNA modulation and miRNA/gene networks in post-MI remodeling remain elusive. Furthermore, with an emerging interest to combine cell transplantation with gene therapy, mesenchymal stem cells (MSC) are considered most beneficial of the stem cells in regenerative medicine. We have a paucity of data in genetically modified MSC on their mobilization within infarcted myocardium. We identified a panel of novel dysregulated miRNAs in the wild type (WT) mice subjected to MI using conventional miRNA array. These miRNAs were restored in cardiac-specific IκBα triple-mutant mice (3M, resistant to NF-κB activation) mice indicated NF-κB-dependent regulation. Among them, miR-23a and miR-27a were significantly upregulated in MI. Our study has identified PPARγ-GSK3β-Bcl 2 -axis, a bona-fide target for miR-23a/-27a after unbiased in vitro screening. Our hypothesis is that NF-κB-dependent miR-23a/-27a is a pathogenic niche, exacerbates post-MI remodeling through several target pathways; and inhibition of NF-κB, miR-23a/-27a and transplantation of 3M-MSC mitigates the cardiac damage and abrogates the cardiac damage by restoring PPARγ-GSK3β-Bcl 2 -axis. Inhibition of NF-κB normalized miR-23a/-27a expression and reduced CM death in hypoxia/ reoxygenation (H/R) model. Our data also indicated that miR-23a is a key regulator in simulated H/R-induced injury. Inhibition of miR-23a showed reduction of cell death and improved mitochondrial function in H/R model. Interestingly, 3M-MSC showed significant reduction in apoptosis, inflammation and oxidative stress in H/R-induced CM injury, compared to WT-MSC. Our findings conclude that miR-23a/-27a could be a triggering factor and 3M-MSC provides a better protection in post-MI remodelling indicate new mechanistic information for therapeutic benefit.
Prognostic Value of 18F-FDG PET/CT Metabolic Parameters in Surgically Treated Stage I Lung Adenocarcinoma Patients
Authors: Davide Tosi, Sara Pieropan, Maria Cattoni, Gianluca Bonitta, Sara Franzi, Paolo Mendogni, Andrea Imperatori, Nicola Rotolo, Massimo Castellani, Marco Cuzzocrea, Ilaria Schiorlin, Sabrina Casagrande, Diego De Palma, Mario Nosotti, Lorenzo Dominioni
Journal: Clinical Nuclear Medicine (2021)

Purpose of the Report This article aims to explore the prognostic role of 18 F-FDG PET/CT metabolic parameters in stage I lung adenocarcinoma patients. Patients and Methods One hundred eighty pathological stage I lung adenocarcinoma patients were retrospectively reviewed. Semiquantitative analysis of FDG tumor uptake was performed with TrueD software on the Siemens Leonardo workstation. SUV mean and MTV were calculated using SUV threshold of 41% of SUV max ; the total lesion glycolysis (TLG) was calculated as the product of SUV mean and MTV. Correlation was evaluated using Spearman correlation coefficient. Maximally selected rank statistics was performed to detect the optimal cutoff used for dichotomizing each PET parameter (6.5 for SUV mean , 9.6 for SUV max , and 19.1 for TLG). Results Our main finding was the significant correlation between 18 F-FDG PET/CT parameters (SUV mean , SUV max , and TLG) and disease-free survival in pathologic stage I non–small cell lung cancer. SUV mean has the greatest accuracy in recurrence prediction (integrated area under the curve, 0.803; 95% confidence interval, 0.689–0.918). We run the maximally selected rank statistics to provide the classification of observations in 2 groups by a continuous predictor parameter; the free from recurrence rate was significantly greater in patients with SUV mean ≤6.5, SUV max ≤9.6, and TLG ≤19.1. Conclusions Our research supports the hypothesis that SUV mean , SUV max , and TLG are well correlated with free from recurrence rate in stage I adenocarcinoma patients, subjected to pulmonary lobectomy. Our findings also indicate these markers as promising prognostic indicators.
AB0701 ANTIBODY RAPID TEST POSITIVE HEALTH CARE WORKERS AT A GERMAN UNIVERSITY HOSPITAL: FIRST WAVE CHARACTERISTICS
Authors: M. Beck, A. Nieters, M. Rizzi, U. Salzer, J. Thiel, N. Venhoff, N. Peter, H. Eibel, R. Voll, S. Finzel
Journal: Annals of the Rheumatic Diseases (2021)

Background: Freiburg was among the most heavily affected German cities during the first wave of Sars-Cov-2 infections in spring 2020. Consequently, the University Medical Center Freiburg was one of the first hospitals in Germany to treat Covid19 patients. Objectives: To assess the proportion and characteristics of health care workers (HCW) that have been infected during that first wave SARS-CoV-2 serum IgG and IgM antibodies were measured. Methods: HCW (n=902, mean age: 40.7 years) participated in this study, and filled out an epidemiological questionnaire. Serum samples were analysed for SARS-Cov-2 IgG/IgM antibodies via rapid diagnostic test (RT) and via ELISA. Statistical analyses were performed using STATA 14.2. An exposure prevention score was developed to quantify the adherence to preventive measures in everyday life. Results: 902 HCW were tested by RT, and 499 by ELISA. In total, 11.5% of recruited HCW were antibody-positive in the RT, 12.2% in the ELISA. 87.5% of RT positives, 98% of ELISA-positives reported symptoms, compared to 74.6% and 78% of negatives, respectively. Symptoms such as cough (57%/46%), loss of smell and taste (34%/5.2%), fatigue (68%/45%), fever (48%/24%), body aches (45%/22%), and headaches (58%/46%) were reported by significantly more RT positives compared to negatives. The respective differences were even more pronounced (p&lt;0.001) among ELISA-positives compared to negatives with &gt;50% of those positive reported impaired smell or taste compared to less than 7% among the group of ELISA-negatives (p&lt;0.00001). In logistic regression models, shift work and belonging to the lowest quartile of the exposure prevention score were significantly associated with seropositivity in both tests. Exposure towards children was inversely associated with seropositivity, however, in the finally adjusted model only significant for those that were RT-positive, but not ELISA-positive, reflecting the lower specificity of the former. Conclusion: The endemic infection rate in HCW was high. HCW adhering to preventive measures in everyday life had lower infection rates. Disclosure of Interests: Manuel Beck: None declared, Alexandra Nieters: None declared, Marta Rizzi: None declared, Ulrich Salzer: None declared, Jens Thiel Speakers bureau: BMS, Nils Venhoff Speakers bureau: Novartis, Nicole Peter: None declared, Hermann Eibel: None declared, Reinhard Voll Speakers bureau: Novartis, Grant/research support from: BMS, Pfizer, Novartis, Stephanie Finzel Speakers bureau: Novartis
The FADS mouse: A novel mouse model of atopic keratoconjunctivitis
Authors: Satoshi Nunomura, Isao Kitajima, Yasuhiro Nanri, Midori Kitajima, Naoko Ejiri, I-Shuan Lai, Naoko Okada, Kenji Izuhara
Journal: Journal of Allergy and Clinical Immunology (2021)
Association of Socioeconomic Status With Alpha Omega Alpha Honor Society Membership Among Medical Students
Authors: Mytien Nguyen, Hyacinth R. C. Mason, Patrick G. O’Connor, Marcella Nunez-Smith, William A. McDade, Darin Latimore, Dowin Boatright
Journal: JAMA Network Open (2021)

study involved a 2-year time frame and may not represent historical trends in AΩA membership.However, to our knowledge, this study is the largest and only examination of AΩA membership by socioeconomic status to date.Although AΩA membership has been recognized as a marker of merit, our findings suggest that AΩA membership may also be an indicator of privilege.Medical schools must ensure that the learning environment allows all students to thrive irrespective of their backgrounds.
Multicentre Retrospective Analysis of Chronic Lymphocytic Leukaemia Patients Treated with Idelalisib, Real World Data from the UK and Republic of Ireland - a Cohort of 68 Patients
Authors: Fiona Fernando, Jessica Griffin, James Taylor, Marquita Camilleri, Lisa Lowry, Adrian Maraj, Piers Patten, Elvis Aduwa, Alison Delaney, Satyen Gohil, Sunil Iyengar, Vashti Ragoonanan, Nimish Shah, Cloke Rachel, Atchamamba Bobbili, Cesar A. Gomez, Rajesh Krishna, Helen Eagleton, Uzma Faruqi, Amit Nathwani, Maureen Heath, Anupama Jaggia, Robert Michael Ayto
Journal: Blood (2017)
POS0665 TRAJECTORIES OF GLUCOCORTICOID-THERAPY IN EARLY RHEUMATOID ARTHRITIS: FIRST RESULTS OF A SCOPING SYSTEMATIC REVIEW AND META-ANALYSIS OF OBSERVATIONAL COHORT STUDIES
Authors: A. Palmowski, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2021)

Background: Glucocorticoids (GCs) are regularly used as a bridging therapy in early rheumatoid arthritis (eRA). As long-term treatment, especially at higher dosages, may lead to undesirable adverse events, GCs should be tapered as rapidly as clinically feasible. Objectives: To assess real-world trajectories of GC-therapy initiated in patients with eRA and in methotrexate-naïve RA patients. Methods: We conducted a scoping search in MEDLINE (via PubMed) to find articles (years 2005 – 2020) reporting on eRA (or methotrexate-naïve RA) patients from observational cohorts who start or take GCs at baseline. Articles had to describe either dosages or proportions of patients who took GCs or were able to taper GCs at two (minimum) pre-specified time points. The articles were screened by one reviewer (AP). Random-effects meta-analyses pooled results per outcome and time point if ≥3 studies were available. R software with package metafor was used for statistical analyses. A research protocol was published with protocols.io (10.17504/protocols.io.bpyfmptn). Results: Our highly specific search strategy yielded 165 results. Twelve articles on nine cohorts were finally included. Eight cohorts originated in Europe, one in Africa. At baseline, about half of the patients with eRA were prescribed GCs with a mean dosage of 8mg/d prednisone equivalent (fig 1 ). Over time, both the proportion taking GCs and the mean dosage declined. There was substantial heterogeneity between studies. Conclusion: Our results indicate that GCs remain regularly used drugs in eRA patients and in methotrexate-naïve patients with RA. While about 40% of patients still receive GCs after 24 months, mean dosages were tapered to “low” dosages (≤7.5mg/d prednisone equivalent) 1 in all cohorts that reported respective data. Heterogeneity might be caused by country-specific differences. Unfortunately, the validity of sensitivity analyses would be poor due to the paucity of published data regarding GC dosages and proportions of patients taking GCs in observational RA cohorts. Major limitations of this scoping review are the very specific (and consequently less sensitive) search strategy and that the screening was conducted by one reviewer only. References: [1]Buttgereit F, Da Silva JAP, Boers M, et al. Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology. Ann Rheum Dis 2002;61(8):718-22. doi: 10.1136/ard.61.8.718. Figure 1. Meta-analyses of proportions taking glucocorticoids and mean dosages at baseline and 24 months. GCs: Glucocorticoids; CI: Confidence interval. Disclosure of Interests: None declared
POS0038 THE INFLUENCE OF AGE ON THE PREVALENCE OF INFLAMMATORY AND POST-INFLAMMATORY MRI LESIONS IN THE SACROILIAC JOINTS OF PATIENTS WITH AND WITHOUT AXIAL SPONDYLOARTHRITIS
Authors: X. Baraliakos, S. Tsiami, A. Kühn, M. Fruth, J. Braun
Journal: Annals of the Rheumatic Diseases (2021)

Background: Axial spondyloarthritis (axSpA) is clinically characterized by chronic inflammatory back pain and by inflammatory and structural changes in the sacroiliac joint (SIJ) as assessed by magnetic resonance imaging (MRI). Several studies have reported high rates of bone marrow edema (BME) suggestive of inflammatory SIJ changes in up to 20% of individuals in the general population &lt;45 years. An update of the definition of a positive MRI of the SIJ in axSpA for classification purposes, based on the number of slices or quadrants showing BME or structural changes such as erosions or fat lesions (FL), was recently published by ASAS. Objectives: To compare the influence of age on the prevalence of inflammatory and structural MRI changes in the SIJ of patients with chronic low back pain diagnosed with axSpA or non-SpA. Methods: MRIs of the SIJ of patients referred for differential diagnosis of back pain who were finally diagnosed with axSpA or not by experienced rheumatologists, were evaluated using semi-coronal STIR and T1-weighted MRI sequences. All images were scored blinded to, age, sex and diagnosis for the occurrence of BME, FL, erosions and ankylosis on the level of SIJ-quadrants (SIJ-Q). Patient groups were built based on decade of age (until 29, 30-39, 40-49 and ≥50 years). Results: A total of 309 patients (175 axSpA and 134 non-SpA) with complete MRI sets were included in the analysis. The mean age was 38.5±11.4 and 43.4±13.8, 66.9% and 35.8% were male, the mean CRP was 1.6±2.4 and 1.1±2.1mg/dl and the median back pain symptom duration was 48 and 60 months, respectively. The number of SIJ-Q with BME and erosions was significantly higher in axSpA vs. non-SpA independent of the age group (Table 1). In comparison, with exception of the patients in the oldest population (≥50 years), the number of SIJ-Q with FL and the number of patients with at least one FL was not different between subgroups, while the number of erosions and FL but not BME was higher in both groups with increasing age. In the univariate analysis, only female sex was significantly associated with higher occurrence of FL. Conclusion: Despite a relatively high prevalence in non-SpA patients, BME and erosions were significantly more frequent in axSpA independent of age, while the presence of FL was not different between groups. FL and erosions are increasingly found in older age groups independent of diagnosis. These data are relevant for the interpretation of MRI findings in the SIJ of patients suspicious of axSpA. Table 1. Comparison of MRI findings between axSpA and non-SpA patients at different age groups Disclosure of Interests: None declared.
Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19
Authors: Andrew Kam Ho Wong, Isaac Woodhouse, Frank Schneider, Deanna A. Kulpa, Guido Silvestri, Cheryl L. Maier
Journal: Cell Reports Medicine (2021)

The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.
POS1306 TREATMENT STRATEGIES IN CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS (CMRO) OR CHRONIC NON-BACTERIAL OSTEOMYELITIS (CNO): SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: R. Dos-Santos, C. Gomez-Vieites, D. Fernández Fernández, I. González Fernández, A. Souto Vilas, E. Perez-Pampín, A. Mera Varela
Journal: Annals of the Rheumatic Diseases (2021)

Background: Glucocorticoids (GC), bisphosphonates (BP), non-steroidal anti-inflammatory drugs (NSAID) and classical synthetic or biological disease-modifying antirheumatic drugs (cs/bDMARD) have been employed in the treatment of chronic recurrent multifocal osteomyelitis (CRMO) or chronic non-bacterial osteomyelitis (CNO). 1, 2 This one is a rare bone childhood illness and none treatment guidelines have been carried out till present. 3 Objectives: To asses which treatment schedule employed in CRMO had the best response rates and try to expose a treatment recommendation. Methods: A systematic literature review was made using Medline, Embase, Cochrane library and the Web of Science databases. The search strategy focused on synonyms of CRMO. A prevalence meta-analysis was performed to evaluate each treatment response. Stata 15.1 was used to perform statistical analysis. Results: The search identified 1883 articles, of which 43 were finally selected. Complete response rate reached with NSAIDs was acceptable [50% (CI95% 40-60)]. Lower response rates were reached by GC treatment [44% (CI95% 25-63)] or csDMARD [38% (CI95% 28-48)]. The best complete response rates were reached by bDMARD and BP treatments [69% (CI95% 56-82) and 73% (CI95% 62-84), respectively]. Conclusion: This review and meta-analysis supports, taking into account its remission rates and its risk-benefit profile, NSAIDs as potential first-line agents in CRMO treatment. bDMARD and BP have reached the higher remission rates, turning into helpful treatment alternatives. There is not any treatment guidelines driving CRMO patients, but this analysis could help to select a suitable agent for each patient. Decision-making should be individualized. References: [1]Wipff J, Costantino F, Lemelle I, et al . A large national cohort of French patients with chronic recurrent multifocal osteitis. Arthritis &amp; Rheumatol. 2014;67(4):1128-1137. [2]Zhao Y, Wu E Y, Oliver M S, et al. Consensus treatment plans for chronic nonbacterial osteomielitis refractory to nonsteroideal anti-inflammatory drugs and/or with active spinal lesions. Arthritis Care Res. 2018;70(8):1228-1237. [3]Menashe SJ, Aboughalia H, Zhao Y, et al . The many faces of pediatric chronic recurrent multifocal osteomyelitis (CRMO): a practical location- and case-based approach to differenciate CRMO from its mimics. J Magn Reson Imaging. 2020;e27299. Disclosure of Interests: None declared
Antibacterial approaches in tissue engineering using metal ions and nanoparticles: From mechanisms to applications
Authors: Maria Godoy-Gallardo, Ulrich Eckhard, Luis M. Delgado, Yolanda J.D. de Roo Puente, Mireia Hoyos-Nogués, F. Javier Gil, Roman A. Perez
Journal: Bioactive Materials (2021)

Bacterial infection of implanted scaffolds may have fatal consequences and, in combination with the emergence of multidrug bacterial resistance, the development of advanced antibacterial biomaterials and constructs is of great interest. Since decades ago, metals and their ions had been used to minimize bacterial infection risk and, more recently, metal-based nanomaterials, with improved antimicrobial properties, have been advocated as a novel and tunable alternative. A comprehensive review is provided on how metal ions and ion nanoparticles have the potential to decrease or eliminate unwanted bacteria. Antibacterial mechanisms such as oxidative stress induction, ion release and disruption of biomolecules are currently well accepted. However, the exact antimicrobial mechanisms of the discussed metal compounds remain poorly understood. The combination of different metal ions and surface decorations of nanoparticles will lead to synergistic effects and improved microbial killing, and allow to mitigate potential side effects to the host. Starting with a general overview of antibacterial mechanisms, we subsequently focus on specific metal ions such as silver, zinc, copper, iron and gold, and outline their distinct modes of action. Finally, we discuss the use of these metal ions and nanoparticles in tissue engineering to prevent implant failure.
Toward higher-performance bionic limbs for wider clinical use
Authors: Dario Farina, Ivan Vujaklija, Rickard Brånemark, Anthony M. J. Bull, Hans Dietl, Bernhard Graimann, Levi J. Hargrove, Klaus-Peter Hoffmann, He Huang, Thorvaldur Ingvarsson, Hilmar Bragi Janusson, Kristleifur Kristjánsson, Todd Kuiken, Silvestro Micera, Thomas Stieglitz, Agnes Sturma, Dustin Tyler, Richard F. ff. Weir, Oskar C. Aszmann
Journal: Nature Biomedical Engineering (2021)