tbuckley/cabot-search huggingface dataset:
AB0076 THE ROLE OF MACROPHAGE MIGRATION INHIBITORY FACTOR IN ACTIVITY AND PROGRESSION OF ANKYLOSING SPONDYLITIS
Authors: Y. Gazar, M. Hanafy, M. Elrefi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Ankylosing Spondylitis (AS) is a chronic inflammatory form of arthritis that predominantly affects the axial joints and has a global prevalence of 1%. Disease progression is marked by osteoproliferation and bone fusion in the axial joints, causing considerable loss of mobility. Migration Inhibitory Factor (MIF) is a potent pro-inflammatory cytokine implicated in several diseases. Elevated serum MIF levels have been reported in AS the role of MIF in bone formation has been a subject of controversy. Objectives: Detection the level of Migration Inhibitory Factor in Ankylosing Spondylitis patients and correlate the level with disease activity and progression. Methods: This cross-sectional case-control study were concluded upon 70 randomly selected people from internal medicine department in Kobry El-kobba Military Hospital and from rheumatology and rehabilitation department in EL-Hussein university hospital. The population study were divided into two groups: Group A: (50) Patients with Ankylosing Spondylitis (AS) who met the European Spondyloarthropathy Study Group (ESSG) criteria for AS (30) and Group B: (20) Healthy controls. Serum MIF by ELISA were measured. X-rays cervical &amp;lumbosacral vertebrae (dorsal, lateral) views were obtained. m-SASS score (based on radiographic findings to detect progression) were assessed. MSK U/S on Tendo Achilles affected in AS patients were done. Results: the mean age of all patients was (38.2 ± 8.4) years. Regarding gender of the patients, the majority (65.7%) of patients were males, while (34.3%) were females. (88%) of AS patients had cervical erosion or sclerosis, (46%) had dorsal erosion or sclerosis, (92%) had lumbosacral erosion or sclerosis, with m-SASS score of (11 ± 6.1). Regarding musculoskeletal U/S, (72%) had evidence of inflammation and erosion. Highly significant increase in ESR, CRP and MIF levels in A group; compared to control B group; with highly significant statistical difference (p &lt; 0.01). the increase in smoking, ESR and MIF level; had an independent effect on increasing the probability of progression occurrence; with significant statistical difference (p &lt; 0.05 respectively). MIF level at a cutoff point (&gt;51) predicted patients with progression, with fair accuracy (74%), sensitivity= 53% and specificity= 94% (p = 0.0056). Conclusion: MIF ply an important role in the pathogenesis of Ankylosing Spondylitis and has a link between chronic inflammation, new bone formation and disease progression and can be used as indicator for activity and disease progression. Disclosure of Interests: None declared
POS0320 POOR PROGNOSIS PREDICTION IN ANTI-MDA5 POSITIVE DERMATOMYOSITIS ASSOCIATED WITH INTERSTITIAL LUNG DISEASE: THE CROSS-CAR DECISION TREE MODEL
Authors: L. Wang, C. Lv, F. Yuan, J. Li, M. Wu, Z. Da, H. Wei, L. Zhou, S. Yin, J. Wu, W. Tan
Journal: Annals of the Rheumatic Diseases (2021)

Background: The prognosis of anti-melanoma differentiation-associated gene 5 positive dermatomyositis (anti-MDA5+ DM) – associated interstitial lung disease (ILD) is poor and heterogeneity. Objectives: The aim of this study was to evaluate prognostic factors and to develop a simple and generally applicable bedside decision tree model for predicting outcomes in patients with anti-MDA5+ DM and to guide treatment. Methods: We analyzed data for 246 anti-MDA5+ DM patients from Myositis Study Group-Jiangsu, a multicenter cohort across eighteen tertiary hospitals in Jiangsu province, from March 2019 to October 2020. The primary end point was all-cause death, and the secondary end point was occurring of rapidly progressive-ILD (rp-ILD). We used a multivariable Cox proportional hazards model to identify the independent prognostic risk factors of death and rp-ILD respectively. A decision-tree prediction model was developed by using data from 10 hospital of southern region (n=163), with validation by using contemporaneous data from northern region (n=83). Results: To assess the risk of rp-ILD, we developed a combined risk score, the CROSS score, that included the following values and scores: C-reactive protein (≤8mg/L, 0; &gt;8mg/L, 3), anti-Ro52 antibody (negative, 0; positive, 4), Sex (Female, 0; Male, 2) and Short course of disease (More than 3 months, 0; Less than 3 months, 2). The mortality risk was identified by the CAR score, including C-reactive protein (≤8mg/L, 0; &gt;8mg/L, 1), Alanine Transaminase (≤50units/L, 0; &gt;50units/L, 1) and rp-ILD (non-rpILD, 0; rp-ILD, 3). We divided patients into three risk groups according to the CROSS score: low, 0 to 3; medium, 4 to 7; and high 8-11. And then Use of a simple decision tree prediction model permitted stratification into three different outcome prediction groups. High-risk patients had significantly higher mortality rates than low- and medium-risk patients in both discovery and validation cohorts (p &lt; 0.0001). Conclusion: The CROSS-CAR decision tree model is easy to evaluate the poor prognostic risk in MDA5+ DM patients during any follow-up period. Unnecessary lung examination, such as chest CT scan and arterial blood gas analysis was avoided in low- and medium- rpILD risk patients. The special ambulance, with red cross sign tagged on car in China, may help to screen the high risk patients and to guide further treatment. Disclosure of Interests: None declared
68Ga-FAPI PET/CT Imaging of Graves Ophthalmopathy in a Patient With Esophageal Cancer
Authors: Huipan Liu, Xiao Yang, Yingwei Wang, Peng Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-FAPI PET/CT has been used in the assessment of a variety of malignancies. In addition, FAPI uptake in nonmalignant diseases has also been reported. Herein, we present a case of Graves ophthalmopathy detected by 68 Ga-FAPI PET/CT.
Corrigendum re: “Robot-assisted Level II–III Inferior Vena Cava Tumor Thrombectomy: Step-by-Step Technique and 1-Year Outcomes” [Eur Urol 2017;72:267–74]
Authors: Sameer Chopra, Giuseppe Simone, Charles Metcalfe, Andre Luis de Castro Abreu, Jamal Nabhani, Mariaconsiglia Ferriero, Alfredo Maria Bove, Rene Sotelo, Monish Aron, Mihir M. Desai, Michele Gallucci, Inderbir S. Gill
Journal: European Urology (2021)
Biomarkers in Nonmetastatic Castrate-Resistant Prostate Cancer
Authors: David D. Yang, Brandon A. Mahal, Luke R. G. Pike
Journal: JAMA Oncology (2021)

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AB0395 RENAL INVOLVEMENT IN HENOCH-SCHÖNLEIN PURPURA
Authors: N. Ben Chekaya, S. Daada, M. Brahim, I. Chaabene, R. Klii, M. Kechida, S. Hammami
Journal: Annals of the Rheumatic Diseases (2021)

Background: Henoch-Schönlein purpura (HSP), also known as rheumatic purpura, is an immune complex vasculitis affecting small vessels with dominant IgA deposits. Clinical manifestations mainly involve cutaneous purpura, arthralgias and/or arthritis, acute enteritis and glomerulonephritis. HSP is more common among children than adults. Kidney damage is the principal prognostic determinant in HSP. The aim of this study is to evaluate the renal manifestations of HSP. Objectives: The aim of this study is to evaluate the renal manifestations of HSP. Methods: This was a retrospective study of 35 patients with diagnosed HSA, who were admitted between the time period may 2008 and november 2018. All of these patients met the American College of Rheumatology classification criteria for a diagnosis of HSP. Renal involvement was defined as the presence of proteinuria or hematuria. Results: The study group consisted of 35 patients, 20 women (57%) and 15 men (43%). The mean age was 48.8± 18.7 years. The incidence rates of skin, joint, gastrointestinal and central nervous system involvement were 91.4, 77.1, 54.2 and 2.8%, respectively. Elevated serum IgA levels occurred in 5.7 %. Six patients (17.1%) were given corticosteroids during the first 3 months of their HSP, which were indicated for severe gastrointestinal (n=5) or renal involvement (n=1). Eighteen of the thirty five patients (51.42%) had renal involvement. There were 12 women and six men. All patients had proteinuria (100%). Hematuria has been identified in 11 patients (61.1%) and renal insufficiency in 4 patients (22.2%). The renal involvement was mainly detected in the first month. Renal biopsy was affected in four patients (22.2%). An endocapillary glomerulonephritis was found in 3 patients and an extra capillary necrotizing glomerulonephritis in one patient. The immunofluorescence showed the presence of IgA deposits in 4 patients. Conclusion: Renal involvement dominates the prognosis for the disease. The most common clinical expression is the association of microscopic hematuria with proteinuria. Disclosure of Interests: None declared
The C Loop of Fifth Epidermal Growth Factor-like Domain of Thrombomodulin Exerts Cytoprotective and Angiogenic Effects in Vitro and In Vivo
Authors: Xiangmin Wang, Bin Pan, Goichi Honda, Yuko Hashimoto, Hiroshi Ohkawara, Kailin Xu, Lingyu Zeng, Takayuki Ikezoe
Journal: Blood (2017)
Pro-cachectic factors link experimental and human chronic kidney disease to skeletal muscle wasting programs
Authors: Francesca Solagna, Caterina Tezze, Maja T. Lindenmeyer, Shun Lu, Guochao Wu, Shuya Liu, Yu Zhao, Robert Mitchell, Charlotte Meyer, Saleh Omairi, Temel Kilic, Andrea Paolini, Olli Ritvos, Arja Pasternack, Antonios Matsakas, Dominik Kylies, Julian Schulze zur Wiesch, Jan-Eric Turner, Nicola Wanner, Viji Nair, Felix Eichinger, Rajasree Menon, Ina V. Martin, Barbara M. Klinkhammer, Elion Hoxha, Clemens D. Cohen, Pierre-Louis Tharaux, Peter Boor, Tammo Ostendorf, Matthias Kretzler, Marco Sandri, Oliver Kretz, Victor G. Puelles, Ketan Patel, Tobias B. Huber
Journal: Journal of Clinical Investigation (2021)

Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of pro-cachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.
AB0020 ACPA ILLUSTRATING THE IMPACT OF IGG FAB-GLYCOSYLATION ON TRANSPLACENTAL TRANSFER OF ANTIBODIES AND THEIR BINDING TO THE NEONATAL FC-RECEPTOR (FCRN)
Authors: M. Volkov, K. Van Schie, A. Bondt, T. Kissel, M. Brinkhaus, A. Bentlage, C. Koeleman, S. De Taeye, R. Dolhain, M. Wuhrer, R. Toes, G. Vidarsson, D. Van der Woude
Journal: Annals of the Rheumatic Diseases (2021)

Background: Fc neonatal receptor (FcRn) is crucial for IgG half-life and transplacental transport. Different sites of IgG carry glycans which may affect binding to FcRn. While the effect of Fc-glycans has been investigated, the impact of Fab-glycosylation (~14% IgG) on IgG-FcRn interaction remains unclear. Anti-citrullinated protein antibodies (ACPA) of rheumatoid arthritis patients exhibit remarkably high Fab-glycosylation (~90%). This makes ACPA an ideal model to investigate how Fab-glycosylation influences IgG-FcRn interaction. Objectives: To investigate the potential impact of IgG Fab-glycosylation on IgG transplacental transfer and interaction with FcRn. Methods: To investigate transplacental transport of ACPA and total IgG, serum of ACPA-positive RA patients (mothers) as well as of healthy mothers and their respective newborns was analyzed. IgG Fab- and Fc-glycosylation was investigated with liquid chromatography and mass-spectrometry. Furthemore, ACPA monoclonal IgG were produced and glycoengineered to acquire several variants of the same monoclonal antibody differing only in their glycosylation profile. These glycovariants were then used to investigate the impact of Fab-glycans on the affinity of IgG for FcRn. Surface plasmon resonance (SPR) and affinity chromatography were implemented. Results: When measured in mothers’ serum and cord blood samples, Fab-glycosylation of IgG antibodies was ~20% lower in newborns compared to their mothers, which was observed for ACPA IgG, non-ACPA IgG in RA patients and total IgG of healthy controls (Figure 1). This may indicate that transplacental transfer of Fab-glycosylated antibodies is impaired. SPR results suggested that presence of Fab-glycans slightly lowered the affinity of IgG for FcRn. However, presence of Fab-glycans did not have a significant effect on the results of FcRn affinity chromatography. Together, these results suggest that Fab-glycans may impair association of IgG with FcRn, while dissociation likely stays intact. Conclusion: Our results suggest that Fab-glycans inhibit IgG-FcRn binding which negatively affects the transplacental transfer of Fab-glycosylated IgG. The impact of Fab-glycosylation on IgG half-life requires further investigation. Figure 1. Disclosure of Interests: Mikhail Volkov: None declared, Karin van Schie: None declared, Albert Bondt: None declared, Theresa Kissel: None declared, Maximilian Brinkhaus Grant/research support from: argenx, Arthur Bentlage: None declared, Carolien Koeleman: None declared, Steven de Taeye Grant/research support from: Genmab, Radboud Dolhain: None declared, Manfred Wuhrer: None declared, Rene Toes: None declared, Gestur Vidarsson: None declared, Diane van der Woude: None declared
AB0810 COST-EFFECTIVENESS ANALYSIS OF THE CLINICAL APPROACH FOR RA PATIENTS IN THE EARLY PHASE VERSUS THOSE IN THE ESTABLISHED PHASE FROM A FOURTH-LEVEL HEALTH SERVICE PROVIDER INSTITUTION IN COLOMBIA
Authors: C. Sarmiento Peña, G. Quintana Lopez, J. A. Díaz
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease that without treatment causes disability, pain, quality of life impairment, and premature mortality. It causes significant economic repercussions on patients, their families, and the health system. The costs of RA for Sanitary Systems are described in terms of medications and hospitalization. Also, the cost of treatment for patients whose disease was not adequately controlled from an early stage may involve joint replacement surgery and prolonged hospitalizations. Objectives: To determine and analyze the cost-effectiveness of the clinical approach to rheumatoid arthritis in a cohort of patients in the early phase versus a cohort of patients in the established phase from a fourth-level Health Service Provider Institution in Colombia, from the perspective of the third-party payer with a time horizon of six-months. Methods: An economic evaluation of the cost-effectiveness of the clinical approach was carried out in the early phase versus the established phase in a cohort of patients from May 2013 until December 2018, with rheumatoid arthritis from a fourth-level Health Service Provider Institution in Colombia, from the perspective of the third-party payer with a time horizon of six-months. The costs and effectiveness of each of the phases were estimated. A decision tree model was created, and the incremental cost-effectiveness ratio was calculated. The deterministic and probabilistic sensitivity analysis was performed. Results: The early phase clinical approach for patients with rheumatoid arthritis represents savings of approximately 600 USD per patient in remission or low disease activity level in the first 6 months of follow-up from the perspective of the third-party payer. Conclusion: The clinical approach to rheumatoid arthritis in the early phase is a less costly and more effective alternative versus established phase and generates savings for the third-party payer with a time horizon of six-months. Figure 1. Acceptability curve Disclosure of Interests: None declared
POS0957 THE PREVALENCE AND FACTORS RELATED TO SLEEP APNOEA IN ANKYLOSING SPONDYLITIS
Authors: H. Forsblad-D’elia, A. Wiginder, C. Sahlin-Ingridsson, M. Geijer, K. Franklin, A. Blomberg
Journal: Annals of the Rheumatic Diseases (2021)

Background: An increased prevalence of obstructive sleep apnoea (OSA) has been suggested in ankylosing spondylitis (AS), but few controlled studies have been performed. Objectives: We thus aimed to study the prevalence of OSA in patients with AS compared to controls and to study if disease-related and non-disease-related factors were determinants of OSA in AS patients. Methods: One hundred and fifty-five patients with AS were included in the Backbone study that investigates severity and comorbidities in AS. Controls were recruited from the Swedish CardioPulmonary bioImage Study (SCAPIS). Participants were asked to be examined with a home sleep-monitoring device during one night’s sleep to evaluate the presence of OSA. For each AS patient, 45-70 years, four controls were matched for sex, age, weight and height. OSA was defined as an apnoea-hypopnea-index ≥5 events/hour. Results: In total, 63/155(40.6%) patients with AS were examined with a home sleep-monitoring device out of which 46 patients were 45-70 years and therefore matched (mean age 57.2±7.5years, 30(65.2%) men) with 179 controls (mean age 57.2±4.5years, 123(68.7%) men). Twenty-two out of 46(47.8%) patients with AS vs. 91/179(50.8%) controls had OSA, p=0.72. No differences measurements evaluating OSA were noted in AS vs. controls. In logistic regression analysis, based on all 63 examined AS-patients, several AS-related variables were associated with OSA but after adjusting for age and sex, only higher age and BMI, remained to be significant determinants of OSA, Table 1. Table 1. Univariable and age- and sex-adjusted logistic regression analyses with obstructive sleep apnoea as dependent variable in 63 patients with ankylosing spondylitis. Variables Univariable logistic regression analyses, Odds Ratio (95%CI) P Age- and sex-adjusted logistic regression analyses, Odds Ratio (95%CI) P Sex, male 1.9(0.6-5.5) 0.25 1.5(0.4-4.8) 0.53 Age 1.1(1.0-1.2) 0.002 1.1(1.0-1.2) 0.002 BMI 1.4(1.1-1.7) 0.001 1.6(1.2- 2.2) 0.001 Duration of symptoms 1.1(1.0-1.1) 0.028 1.0(0.9-1.1) 0.79 BASMI 1.9(1.3-2.9) 0.002 1.5(0.9 -2.5) 0.87 BASFI 1.4(1.0-2.0) 0.038 1.3(0.9-2.0) 0.88 ≥1 Syndesmophyte 3.9(1.3-12.2) 0.017 3.0(0.8-11.3) 0.10 mSASSS 1.0(1.0-1.1) 0.047 1.0(0.98-1.05) 0.25 Metabolic syndrome 4.3(1.5-12.9) 0.008 1.4(0.3-6.6) 0.69 Epworth Sleep Scale 1.2(1.0-1-3) 0.023 1.2(1.0-1.4) 0.29 Conclusion: In this case-control study, patients with AS did not have a higher prevalence of OSA compared to controls. AS patients with OSA had higher BMI and were older compared to patients without OSA. Disclosure of Interests: None declared.
Zinc alloy-based bone internal fixation screw with antibacterial and anti-osteolytic properties
Authors: Xinhua Qu, Hongtao Yang, Bo Jia, Minqi Wang, Bing Yue, Yufeng Zheng, Kerong Dai
Journal: Bioactive Materials (2021)

There is no targeted effective treatment for patients undergoing internal fixation surgery/two-stage total joint revision surgery with a high risk of postoperative infection and osteolysis, while the rate of reoperation due to infection and osteolysis remains high. In this study, we report a pioneering application of implants made of biodegradable Zn–Ag alloy with active antibacterial and anti-osteolytic properties in three classical animal models, illustrating antibacterial, anti-osteolysis, and internal fixation for fractures. The antibacterial activity of the Zn–2Ag alloy was verified in a rat femur osteomyelitis prevention model, while the anti-osteolytic properties were evaluated using a mouse cranial osteolysis model. Moreover, the Zn–2Ag based screws showed similar performance in bone fracture fixation compared to the Ti–6Al–4V counterpart. The fracture healed completely after 3 months in the rabbit femoral condyle fracture model. Furthermore, the underlying antibacterial mechanism may include inhibition of biofilm formation, autolysis-related pathways, and antibiotic resistance pathways. Osseointegration mechanisms may include inhibition of osteoclast-associated protein expression, no effect on osteogenic protein expression, and no activation of related inflammatory protein expression. The empirical findings here reveal the great potential of Zn–Ag-based alloys for degradable biomaterials in internal fixation surgery/two-stage total joint revision surgery for patients with a high risk of postoperative infection and osteolysis.
Author Correction: Nuclear mechanosensing drives chromatin remodelling in persistently activated fibroblasts
Authors: Cierra J. Walker, Claudia Crocini, Daniel Ramirez, Anouk R. Killaars, Joseph C. Grim, Brian A. Aguado, Kyle Clark, Mary A. Allen, Robin D. Dowell, Leslie A. Leinwand, Kristi S. Anseth
Journal: Nature Biomedical Engineering (2021)