tbuckley/cabot-search huggingface dataset:
OP0045 Prognosis of the pulmonary arterial aneurysms in behcet’s disease: an update
Authors: V Hamuryudan, T Er, M Tanverdi, I Fresko, S Yurdakul, H Yazici
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In a previous study<sup>1</sup> our group has reported a 50% mortality rate among 24 patients with Behcet’s disease (BD) having pulmonary arterial aneurysms (PAA). The delay in diagnosing and initiating treatment for this complication could have a role in this outcome. <h3>Objectives</h3> To determine whether the outcome of PAA in our centre has changed since our previous report and to assess the possible factors that might influence the prognosis. <h3>Methods</h3> Patients diagnosed as having PAA after 1992 (Group 2) were identified retrospectively. Their clinical findings and outcome were compared with those of the patients in the previous report (Group 1). <h3>Results</h3> Fifteen additional BD patients (all male) were diagnosed as having PAA. All were treated with cyclophosphamide and prednisolone. Their mean age (32 ± 1.8 SEM years), disease duration (51.5 ± 6.8 SEM months), pathergy positivity (92%), HLA B5 status (60%) and other clinical manifestations were comparable to those of the patients in Group 1. The interval from the first symptom of PAA until the initiation of the treatment was significantly shorter in Group 2 compared to Group 1 (1.7 ± 0.6 SEM months vs. 6.4 ± 1.5 SEM months; p = 0.026). The mean follow ? up time after the initiation of treatment did not significantly differ between groups (50.9 ± 8.5 SEM months for Group 2 and 45.3 ± 11.4 SEM months for Group 1). There were 2 deaths in Group 2 (13%) and 14 deaths in Group 1 (58%). A Kaplan ? Meier analysis revealed a significantly better survival for patients in Group 2 compared to the patients in Group 1 (log rank = 6.8; p = 0.009). When only the patients who had received cyclophosphamide (with or without prednisolone) were considered in the analysis (17 patients from Group 1 and all patients from Group 2), the outcome was still better for the patients in Group 2 (log rank = 3.4; p = 0.065). <h3>Conclusion</h3> Early recognition and most probably cyclophosphamide usage improve the outcome of PAA. <h3>Reference</h3> Hamuryudan V, Yurdakul S, Moral F, <i>et al</i>. Pulmonary arterial aneurysms in Behcet’s syndrome: a report of 24 cases. Br J Rheumatol. 1994;33:48–51
THU0286 THE SYSTEMIC LUPUS INTERNATIONAL COLLABORATING CLINICS (SLICC) FRAILTY INDEX (SLICC-FI) PREDICTS DAMAGE ACCRUAL IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS. DATA FROM A MULTI-ETHNIC, MULTI-CENTER US LUPUS COHORT
Authors: M. F. Ugarte-Gil, J. Dubey, G. Mcgwin, L. Vila, G. S. Alarcon
Journal: Annals of the Rheumatic Diseases (2020)

Background: The Systemic Lupus International Collaborating Clinics (SLICC) Frailty Index (SLICC-FI) has been developed as a predictor of outcomes in SLE patients 1-3 . It combines disease activity, damage, comorbidities and health-related quality of life measures. Objectives: To evaluate the SLICC-FI as a predictor of damage accrual in systemic lupus erythematosus (SLE) patients. Methods: Patients from a multi-ethnic, multi-center US lupus cohort were included. Damage was ascertained with the SLICC/American College of Rheumatology (ACR) damage index (SDI) at last visit. The first visit in which the SLICC-FI could be derived was considered as the baseline visit. Univariable and multivariable Poisson regression models were performed to determine the association between the baseline SLICC-FI and last SDI, adjusted for sex, age at diagnosis, ethnicity, insurance, prednisone daily dose, antimalarial and immunosuppressive drug use at baseline. Age and gender were included a priori in the multivariable model, the other variables were included if they had a p&lt;0.10 in the univariable models. Results: Of the 503 patients included, 454 (90.3%) were female with mean (SD) age 37.1 (12.5) years at diagnosis; 174 (34.6%) were African-American, 144 (28.6%) were Caucasians, 86 (17.1%) Hispanics (Texas), and 99 (19.7%) were Hispanics (Puerto Rico). The mean (SD) baseline SLICC-FI was 0.26 (0.06). The final mean (SD) SDI score was 1.9 (2.2). Higher SLICC-FI scores at baseline predicted greater damage accrual in the univariable analysis [Estimate=5.058, (SE=0.498); p&lt;0.0001]. The SLICC-FI remained associated with damage accrual in the multivariable model, after adjustment for possible confounders [Estimate= 3.561 (SE=0.538); p&lt;0.0001]. Conclusion: The SLICC-FI predicts damage accrual in SLE patients from a multi-ethnic cohort, supporting the importance of this index in the evaluation of SLE patients, combining several aspects of the disease. References: [1]Legge A, Kirkland S, Rockwood K, et al. Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus. J Rheumatol. 2020; 47: 72-81 [2]Legge A, Kirkland S, Rockwood K, et al. Evaluating the Properties of a Frailty Index and Its Association With Mortality Risk Among Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019; 71: 1297-107 [3]Legge A, Kirkland S, Rockwood K, et al. Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI). Arthitis Rheumatol. Epub ahead of print 2019 Oct 21. Disclosure of Interests: Manuel F. Ugarte-Gil Grant/research support from: Jannsen, Pfizer, Jyoti Dubey: None declared, Gerald McGwin: None declared, Luis Vila: None declared, Graciela S Alarcon: None declared
AB0769 THE IMPACT OF BODY MASS INDEX ON DISEASE ACTIVITY AND ENTHESITIS IN PSORIATIC ARTHRITIS
Authors: S. Ganhão, B. M. Fernandes, S. Garcia, F. Pinheiro, M. Rato, E. Mariz, M. Bernardes, L. Costa
Journal: Annals of the Rheumatic Diseases (2020)

Background: Overweight/obesity has increased exponentially in the last decades, becoming a huge Public Health problem. Moreover, an increase in adipose tissue is associated with an increased production of several proinflammatory cytokines and acute phase reactants. Higher BMI has been related with new bone formation including syndesmophytes and enthesophytes. In fact, besides rheumatologic conditions including Psoriatic Arthritis (PsA), enthesopathy can be a consequence of several clinical conditions including metabolic syndrome, mechanical injuries and degeneration. Objectives: To evaluate the effect of body mass index (BMI) on disease activity scores and enthesitis scores in Psoriatic Arthritis. Methods: Retrospective study including all the patients with PsA meeting the CASPAR criteria, beginning first-line biologic therapy at our centre. Demographic and clinical data were collected from the Portuguese database Reumapt. Statistical analysis was performed with SPSS. Continuous variables were compared through Spearman/Pearson correlations. Results: The mean BMI was 26.8 (SD 0.5). In our sample of 119 PsA patients, 21.5% were overweight and 8.3% were obese. The mean age of patients was 46.3 ± 1.03 years; 60 female and 59 male. The median disease duration was 6.8 (0.3-33.8) years. At baseline mean (SD) disease activity variables were: DAS 28 4vESR 4.9 (0.2), ESR 33.2 (2.3) mm/h; CRP 2.35 (0.3) mg/dL, BASDAI 6.6 (0.2), ASDAS 3.9 (0.1), BASMI 3.7 (0.2), BASFI 5.8 (0.3), MASES 1.9 (0.3), SPARCC 2.3 (0.3). There were statistically significant positive correlations between BMI and MASES at baseline (p=0.024, r=0.411) but there weren’t with SPARCC, DAS 28 4vESR, ESR, CRP, BASDAI, ASDAS, BASMI and BASFI. Conclusion: The data showed that patients with higher BMI values had higher enthesitis scores suggesting that overweight/obesity may have a negative impact on enthesopathy. Further studies are still needed to further understand that possible relationship. References: [1]Bakirci S, Dabague J, Eder L, McGonagle D, Aydin SZ. The role of obesity on inflammation and damage in spondyloarthritis: a systematic literature review on body mass index and imaging. Clin Exp Rheumatol. 2019 Apr 29. Disclosure of Interests: Sara Ganhão: None declared, Bruno Miguel Fernandes: None declared, Salomé Garcia: None declared, Filipe Pinheiro: None declared, Maria Rato: None declared, Eva Mariz: None declared, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Lúcia Costa: None declared
Why Healthcare Workers Should Not Be Prioritized in Ventilator Triage
Authors: William Sveen, Armand H. Matheny Antommaria
Journal: The American Journal of Bioethics (2020)

This article refers to:Ethics Lessons From Seattle's Early Experience With COVID-19Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force
Neonatal management and outcomes during the COVID-19 pandemic: an observation cohort study
Authors: Christine M Salvatore, Jin-Young Han, Karen P Acker, Priyanka Tiwari, Jenny Jin, Michael Brandler, Carla Cangemi, Laurie Gordon, Aimee Parow, Jennifer DiPace, Patricia DeLaMora
Journal: The Lancet Child & Adolescent Health (2020)
Stem Cell Therapy Improves Right Ventricular Function and Restores Myocardial Concentrations of Troponin-I and Norepinephrine Uptake Sites in Rats with Pulmonary Hypertension
Authors: A. van der Laarse, S. Umar, T. Hoek, V. Sluiters, P. Steendijk, C. Schutte, W. Bax, D. Pijnappels, D. Atsma, M. Schalij
Journal: Circulation (2010)
Emodin reduces Breast Cancer Lung Metastasis by suppressing Macrophage-induced Breast Cancer Cell Epithelial-mesenchymal transition and Cancer Stem Cell formation
Authors: Qing Liu, Johnie Hodge, Junfeng Wang, Yuzhen Wang, Lianming Wang, Udai P. Singh, Yong Li, Yongzhong Yao, Dawei Wang, Walden Ai, Prakash Nagarkatti, Hexin Chen, Peisheng Xu, E. Angela Murphy, Daping Fan
Journal: Theranostics (2020)

Our previous studies demonstrated that the natural compound emodin blocks the tumor-promoting feedforward interactions between cancer cells and macrophages, and thus ameliorates the immunosuppressive state of the tumor microenvironment. Since tumor-associated macrophages (TAMs) also affect epithelial mesenchymal-transition (EMT) and cancer stem cell (CSC) formation, here we aimed to test if emodin as a neoadjuvant therapy halts breast cancer metastasis by attenuating TAM-induced EMT and CSC formation of breast cancer cells. Methods: Bioinformatical analysis was performed to examine the correlation between macrophage abundance and EMT/CSC markers in human breast tumors. Cell culture and co-culture studies were performed to test if emodin suppresses TGF-β1 or macrophage-induced EMT and CSC formation of breast cancer cells, and if it inhibits breast cancer cell migration and invasion. Using mouse models, we tested if short-term administration of emodin before surgical removal of breast tumors halts breast cancer post-surgery metastatic recurrence in the lungs. The effects of emodin on TGF-β1 signaling pathways in breast cancer cells were examined by western blots and immunofluorescent imaging. Results: Macrophage abundance positively correlates with EMT and CSC markers in human breast tumors. Emodin suppressed TGF-β1 production in breast cancer cells and macrophages and attenuated TGF-β1 or macrophage-induced EMT and CSC formation of breast cancer cells. Short-term administration of emodin before surgery halted breast cancer post-surgery metastatic recurrence in the lungs by reducing tumor-promoting macrophages and suppressing EMT and CSC formation in the primary tumors. Mechanistic studies revealed that emodin inhibited both canonical and noncanonical TGF-β1 signaling pathways in breast cancer cells and suppressed transcription factors key to EMT and CSC. Conclusion: Natural compound emodin suppresses EMT and CSC formation of breast cancer cells by blocking TGF-β1-mediated crosstalk between TAMs and breast cancer cells. Our study provides evidence suggesting that emodin harbors the potential for clinical development as a new effective and safe agent to halt metastatic recurrence of breast cancer.
AB0080 A SYSTEM-LEVEL APPROACH IDENTIFIES A CRITICAL REGULATOR OF CHONDROSARCOMA PROGRESSION
Authors: H. Kim, Y. Cho, J. H. Kim
Journal: Annals of the Rheumatic Diseases (2020)

Background: Chondrosarcomas are cartilaginous tumors that constitute one-third of skeletal system cancers. Chondrosarcomas are capable of transitioning to highly metastatic and treatment-refractory states, resulting in significant patient mortality. However, the molecular events accompanying this behavior remain unknown. Objectives: We aimed to uncover the molecular pathway underlying such tumor progression that confers a higher malignancy to chondrosarcoma. Methods: We conducted unsupervised gene co-expression network analyses using transcriptomes of patients with chondrosarcoma and extracted a characteristic transcription network underlying chondrosarcoma malignancy. By implementing a system-level upstream analysis of this gene network, we identified the transcriptional factor as a key regulator governing chondrosarcoma progression. We unraveled the functional roles of the identified factor in promoting tumor growth and metastasis of chondrosarcomas in the context of their unique microenvironments. Results: By conducting system-level upstream analysis, we identified a factor as a transcriptional regulator that governs the malignancy gene module. The identified factor was upregulated in chondrosarcoma biopsies associated with a high histological grade and conferred chondrosarcoma cells invasiveness and tumor-initiating capacity. In an orthotopic xenograft mouse model, the identified factor modulated local outgrowth and pulmonary metastasis of chondrosarcoma. Pharmacological inhibition of the identified factor in conjunction with the chemotherapy agents such as cisplatin or doxorubicin synergistically enhanced chondrosarcoma cell apoptosis and abolished malignant phenotypes of chondrosarcoma in mice. Conclusion: Our study provides a proof of concept evidence that inhibiting the identified factor suppresses progression of chondrosarcoma and improves the efficacy of chemotherapy in cellular and pre-clinical levels. Taken together, we believe that our findings provide novel molecular insights for the development of new anti-cancer therapies to target chondrosarcomas. References: [1]Gelderblom H, et al. The clinical approach towards chondrosarcoma. Oncologist 13, 320-329 (2008) Disclosure of Interests: None declared
Abstract 15864: Clinical Trial of Autologous CD34 Cell Therapy for Treatment of Coronary Microvascular Dysfunction in Patients With Angina and Non-Obstructive Coronary Arteries
Authors: Noel N Merz, Timothy D Henry, Janet Wei, Michel Corban, Sandy Joung, Christine Kotynski, Michelle Lewis, Ann Schumacher, Ronnda Bartel, William K Sietsema, Douglas W Losordo, Amir Lerman
Journal: Circulation (2019)

Background: Coronary microvascular dysfunction (CMD) has been shown to result in ischemia and cause angina and is linked to adverse clinical outcomes. Thus, CMD may serve as the underlying mechanis...
Role of METTL3-Dependent N6-Methyladenosine mRNA Modification in the Promotion of Angiogenesis
Authors: Mu-Di Yao, Qin Jiang, Yan Ma, Chang Liu, Chuan-Yan Zhu, Ya-Nan Sun, Kun Shan, Hui-Min Ge, Qiu-Yang Zhang, Hui-Ying Zhang, Jin Yao, Xiu-Miao Li, Biao Yan
Journal: Molecular Therapy (2020)

Epigenetic alterations occur in many physiological and pathological processes. N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of m6A modification in pathological angiogenesis remains elusive. In this study, we showed that the level of m6A modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the m6A modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH m6A RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated m6A modification is an important hypoxic stress-response mechanism. The targeting of m6A through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases. Epigenetic alterations occur in many physiological and pathological processes. N6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic mRNAs. However, the role of m6A modification in pathological angiogenesis remains elusive. In this study, we showed that the level of m6A modification was significantly upregulated in endothelial cells and mouse retinas following hypoxic stress, which was caused by increased METTL3 levels. METTL3 silencing or METTL3 overexpression altered endothelial cell viability, proliferation, migration, and tube formation in vitro. METTL3 knockout in vivo decreased avascular area and pathological neovascular tufts in an oxygen-induced retinopathy model and inhibited alkali burn-induced corneal neovascularization. Mechanistically, METTL3 exerted its angiogenic role by regulating Wnt signaling through the m6A modification of target genes (e.g., LRP6 and dishevelled 1 [DVL1]). METTL3 enhanced the translation of LRP6 and DVL1 in an YTH m6A RNA-binding protein 1 (YTHDF1)-dependent manner. Collectively, this study suggests that METTL3-mediated m6A modification is an important hypoxic stress-response mechanism. The targeting of m6A through its writer enzyme METTL3 is a promising strategy for the treatment of angiogenic diseases.
Reply to E. Hindié
Authors: Alexander M. M. Eggermont, Christian U. Blank, Mario Mandala, Georgina V. Long, Victoria G. Atkinson, Stéphane Dalle, Andrew M. Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, James Larkin, Susana Puig, Paolo A. Ascierto, Piotr Rutkowski, Dirk Schadendorf, Rutger Koornstra, Leonel Hernandez-Aya, Anna Maria Di Giacomo, Alfonsus J. M. van den Eertwegh, Jean-Jacques Grob, Ralf Gutzmer, Rahima Jamal, Paul C. Lorigan, Alexander C. J. van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marreaud, Michal Kicinski, Stefan Suciu, Caroline Robert
Journal: Journal of Clinical Oncology (2021)
THU0437 SPECIFIC COMORBIDITIES ENHANCE MONOSODIUM URATE CRYSTAL DEPOSITION IN GOUT: A MULTICENTRE DUAL-ENERGY COMPUTED TOMOGRAPHY STUDY
Authors: T. Pascart, A. Ramon, S. Ottaviani, J. Legrand, V. Ducoulombier, E. Houvenagel, L. Norberciak, P. Richette, F. Becce, P. Ornetti, J. F. Budzik
Journal: Annals of the Rheumatic Diseases (2020)

Background: The reasons explaining why some patients exhibit higher monosodium urate (MSU) crystal burdens than others remain largely unknown. While MSU crystal formation is enhanced by certain factors in vitro such as pH, temperature, and other ion concentrations, it is currently unknown whether comorbidities and clinical features are associated with increased MSU deposition in vivo. Objectives: To determine which factors are associated with the burden of MSU crystal deposition quantified by dual-energy CT (DECT) in urate lowering therapy (ULT)-naive gout patients. Methods: In this multicenter cross-sectional study, DECT scans of knees and feet were prospectively obtained from ULT-naive, or not taking any ULT for more than a year, gout patients. Demographic, clinical (including gout history and comorbidities), and biological data were collected, and their association with DECT MSU crystal volume was analyzed using bivariate and multivariate analyses. A second bivariate analysis was performed by splitting the dataset depending on an arbitrary threshold of DECT MSU volume (1 cm3). Results: A total of 125 gout patients were included, of whom 91 underwent both DECT scans of knees and feet. In bivariate analysis, age (p=0.03), symptom duration (p=0.003), subcutaneous tophi (p=0.004), hypertension (p=0.02), diabetes mellitus (p=0.05), and chronic heart failure (p=0.03) were associated with the total DECT volume of MSU crystal deposition. In multivariate analysis, factors associated with DECT MSU volumes ≥1 cm3 were gout duration (OR for each 10-year increase 3.15 [1.60;7.63]), diabetes mellitus (OR 4.75 [1.58;15.63]), and chronic heart failure (OR 7.82 [2.29;31.38]). The model performance was good with an AUC of 0.816. Conclusion: Specific comorbidities, particularly chronic heart failure, diabetes mellitus, and hypertension, are more strongly associated with increased MSU crystal deposition in knees and feet than gout duration, regardless of serum urate level. Disclosure of Interests: : Tristan Pascart Grant/research support from: Research Grant Horizon Pharma, Consultant of: Novartis, BMS, Sanofi, Pfizer,, Speakers bureau: Novartis, BMS, André Ramon: None declared, Sebastien Ottaviani: None declared, Julie Legrand: None declared, Vincent Ducoulombier: None declared, Eric Houvenagel Speakers bureau: Janssen, Novartis, Laurène Norberciak: None declared, Pascal Richette: None declared, Fabio Becce: None declared, Paul Ornetti: None declared, Jean-François Budzik: None declared
Prevalence and risk factors for high-frequency basal cell carcinoma in the United States
Authors: Audris Chiang, Daniel C. Solis, Howard Rogers, Grace K. Sohn, Hyunje G. Cho, Gillian Saldanha, David Lapidus, Shufeng Li, Kavita Y. Sarin, Jean Y. Tang
Journal: Journal of the American Academy of Dermatology (2020)
What matters most to patients when choosing treatment for mild–moderate asthma? Results from a discrete choice experiment
Authors: Christina Baggott, Paul Hansen, Robert J Hancox, Jo Katherine Hardy, Jenny Sparks, Mark Holliday, Mark Weatherall, Richard Beasley, Helen K Reddel, James Fingleton
Journal: Thorax (2020)

Background An as-needed combination preventer and reliever regimen was recently introduced as an alternative to conventional daily preventer treatment for mild asthma. In a subgroup analysis of the PRACTICAL study, a pragmatic randomised controlled trial of budesonide–formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild asthma, we recently reported that about two-thirds preferred as-needed combination preventer and reliever therapy. The aim of this study was to determine the relative importance of attributes associated with these two asthma therapies in this subgroup of participants who indicated their preferred treatment in the PRACTICAL study. Methods At their final study visit, a subgroup of participants indicated their preferred treatment and completed a discrete choice experiment using the Potentially All Pairwise RanKings of all possible Alternatives method and 1000minds software. Treatment attributes and their levels were selected from measurable study outcomes, and included: treatment regimen, shortness of breath, steroid dose and likelihood of asthma flare-up. Results The final analysis dataset included 288 participants, 64% of whom preferred as-needed combination preventer and reliever. Of the attributes, no shortness of breath and lowest risk of asthma flare-up were ranked highest and second highest, respectively. However, the relative importance of the other two attributes varied by preferred therapy: treatment regimen was ranked higher by participants who preferred as-needed treatment than by participants who preferred maintenance treatment. Conclusions Knowledge of patient preferences for treatment attributes together with regimen characteristics can be used in shared decision-making regarding choice of treatment for patients with mild–moderate asthma. Trial registration number ACTRN12616000377437.