tbuckley/cabot-search huggingface dataset:
POS0429 INTERLEUKIN-4 ACTIVATES EOSINOPHILS AND CCR3-POSITIVE T HELPER CELLS MIGRATION TO FASCIA AND PROMOTES FIBROSIS IN EOSINOPHILIC FASCIITIS
Authors: M. Hosonuma, T. Isozaki, H. Furuya, Y. Yamazaki, Y. Ikari, S. Nishimi, A. Maeoka, S. Ishii, T. Tokunaga, K. Wakabayashi, N. Konishi, S. Fukuse, K. Ishikawa, N. Sakai, K. Inagaki, T. Kasama
Journal: Annals of the Rheumatic Diseases (2021)

Background: Eosinophilic fasciitis (EF) is a rare disease that causes inflammation and fibrosis mainly in the fascia of the extremities with eosinophilia. It has been reported that the hypertrophied fascia in EF shows inflammatory cell infiltration by the lymphocytes and eosinophils and increased expression of fibrosis-related cytokines genes in fibroblast [1]. However, its pathophysiology in the fascia remains unresolved. Objectives: Therefore, we focused on fascial fibroblasts and aimed to determine the role of interleukin-4 (IL-4) in eosinophil and helper T cell infiltration and fibrosis in fascial fibroblast in EF. Methods: Fascial fibroblasts were obtained from fascia biopsy of a patient with EF, and were stimulated with pre- and post-treatment serum of a patient with EF and healthy control, followed by microarray to analyze gene expression. Fascial fibroblasts were stimulated with IL-4 10 ng/mL, and gene expression of IL-4 receptor and CCR3 ligands, CCL7 and CCL11 were measured by qPCR. Transforming growth factor (TGF) -β and periostin in the pre- and post-treatment serum of a patient with EF and conditioned medium of fascial fibroblasts stimulated with IL-4 were measured by ELISA. To examine the role of IL-4 in proliferation, we performed in proliferation assays using fascial fibroblasts treated with IL-4. CCR3-positive T cells in the fascial tissue of EF, dermatomyositis, and polymyositis patients were evaluated by immunostaining. Results: By microarray analysis, CCL7 and CCL11 expression of fascial fibroblasts stimulated with pre-treatment EF serum was higher than that in post-treatment EF serum and control serum. CCL7 and CCL11 mRNA in IL-4 stimulated facial fibroblasts were increased by 5.1-fold and 7.3-fold, respectively. TGF-β and periostin in IL-4 stimulated facial fibroblast conditioned medium were also increased. In addition, TGF-β and periostin in EF serum were gradually decreased by treatment for 4 and 10 weeks, compared to before treatment. Finally, fascial fibroblast proliferation was significantly increased by stimulation with IL-4. Furthermore, infiltration of CCR3-positive T cells was specific to the fascial tissue of EF. Conclusion: In EF, IL-4 enhances the production of CCR3 ligands, TGF-β, and periostin from fascial fibroblasts. As a result, it promotes the migration of eosinophils and CCR3-positive T helper cells to the fascia and fibrosis. These results suggest that inhibition of IL-4 pathway could be a novel strategy for eosinophilic fasciitis. References: [1]Igarashi A, Nashiro K, Kikuchi K, et al. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J Invest Dermatol. 1996 Apr;106(4):729-33. Disclosure of Interests: None declared
AB0189 LIPOPROTEIN ABNORMALITIES IN RHEUMATOID ARTHRITIS PATIENTS
Authors: L. Nacef, Y. Besbes, Y. Mabrouk, H. Ferjani, K. Maatallah, D. Kaffel, S. Besbes, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: The lipid paradox is termed the decreased cholesterol level in rheumatoid arthritis (RA). Nevertheless, the apolipoprotein levels are usually higher than a healthy person and are predictors of cardiovascular events. Objectives: We aimed to describe lipid abnormalities in RA patients and to look for predictor factors of these changes. Methods: The prospective study was carried out on patients with RA who met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. These patients were followed in the rheumatology department of the Kassab Institute. We collected the socio-demographic data, biological and immunological parameters. The lipid assessment included: a measurement of total cholesterol (TC), HDL, LDL, and triglycerides (TG). Lipoproteins APOA1 and APOB were measured. All data were collected after patient consent. Results: Of the 47 patients recruited, 78.7% were female. The mean age was 52.5 ±11.06 [32-76]. The average RA progressed from 86.25 ±63 months [5-288] and was erosive in 81.6% of cases. The rheumatoid factor (RF) was positive in 57.8% of patients, and citrullinated antipeptide antibodies (ACPA) were present in 62.2%. Eight patients had a previous CV history. Mean TC was 4.42 ±1.3 [1.2-7.58], mean HDL was 1.38 ±0.73 [0.18-4.10], mean LDL was 2.55 ±1.16 [0.24-5.54]. The mean TG value was 1.28 ±0.6 [0.24-5.54]. TC elevation was found in 9.1% of cases, HDL in 21.3% of cases, LDL in 5.5% of cases, and TG in 16.4% of cases. Mean APOB/APOA1 ratio was 0.67 ±0.18 [0,46-1,11]. LDL elevation was associated to a high DAS28 (p=0.06, r=0.512). APOA1 was associated to a low DAS28 (p=0.04, r=-0.642). The mean value of APO A1 was 1.36 ±0.21 [0.84-1.81], that of APOB was 0.90 ±0.22 [0.58-1.40]. APOA1 values were lower in patients with high-level LDL (p=0.767). The APOB value was associated with lipid disturbance without significant correlation (p=0.291). Conclusion: Lipid test abnormalities can be found in RA patients outside of any known CV risk factors. APOA1 seems to have a protective effect. Screening and treatment of these abnormalities can prevent CV risk. References: [1]Miguel Bernardes and al. Coronary artery calcium score in female rheumatoid arthritis patients: Associations with apolipoproteins and disease biomarkers. Int J Rheum Dis. 2019;00:1–16. [2]Anna So dergren and al. Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis. PLOS ONE. August 5, 2019. Disclosure of Interests: None declared
Deletion of BMP6 Worsens the Phenotype of Hemojuvelin-Deficient Mice and Attenuates Hepcidin Levels Reached after LPS Stimulation
Authors: Chloé Latour, Céline Besson-Fournier, Ophélie Gourbeyre, Delphine Meynard, Aguilar-Martinez Patricia, Marie-Paule Roth, Helene Coppin
Journal: Blood (2017)
AB0765 PHENOTYPES OF BEHCET’S DISEASE IN DIFFERENT ETHNIC GROUPS
Authors: R. Goloeva, Z. Alekberova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Early diagnosis and identification of predominant organ system involvement in Behcet’s disease (BD) is crucial for identifying most optimal treatment. The study evaluates 6 described phenotypes of BD - cutaneous-mucous, articular, ophthalmic, vascular, neurological and intestinal in different ethnic groups. Objectives: To assess the occurrence of Behcet’s disease (BD) phenotypes in different ethnic groups. Methods: The study included 202 patients with BD from the 5 most common ethnic groups. The male-female ratio was 2.4:1. Patients’ mean age was 31 years [24;37], mean age at the disease onset was 21 years [15;28]; and mean disease duration was 7 years [3;14]. The severity of BD (mild, moderate and severe) was assessed based on the I. Krause’s Clinical Severity Scoring for BD. Results: Severe BD was more often diagnosed in Azerbaijanis and indigenous residents of Dagestan compared to Russians (75 and 70.4% vs. 36.2%), in Armenians - 50% and Chechens - 54.5% out of all BD cases. Russians were significantly more likely to have a neurological phenotype (15.5% vs. 0-9.4% in all other ethnic groups) and intestinal phenotype (36.2% vs. 13.8-22.7 in all other ethnic groups). Azerbaijanis demonstrated higher prevalence of ocular involvement (68.7% versus 36.2% in Russians, 50% - in Chechens and Armenians, and 57% - in Dagestanis). Dagestanis were more likely to have a vascular phenotype (40.7% versus 15.6% in Azerbaijanis and 18.9% in Russians). The male/female ratio among Russian patients was 1:1, among Dagestanis 4.4:1, Azerbaijanis 3.5:1, Chechens and Armenians 2.6: 1. Conclusion: BD phenotypes vary and demonstrate significant association with the patient’s ethnic affiliation therefore, ethnicity should be viewed as the prognostic marker of specific organ-system involvement in case of a disease. Disclosure of Interests: None declared
Astrocytes propel neurovascular dysfunction during cerebral cavernous malformation lesion formation
Authors: Miguel Alejandro Lopez-Ramirez, Catherine Chinhchu Lai, Shady Ibrahim Soliman, Preston Hale, Angela Pham, Esau J. Estrada, Sara McCurdy, Romuald Girard, Riya Verma, Thomas Moore, Rhonda Lightle, Nicholas Hobson, Robert Shenkar, Orit Poulsen, Gabriel G. Haddad, Richard Daneman, Brendan Gongol, Hao Sun, Frederic Lagarrigue, Issam A. Awad, Mark H. Ginsberg
Journal: Journal of Clinical Investigation (2021)

Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. The increased brain endothelial production of NO stabilized HIF-1α in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non–cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.
Time to Reconsider the Importance of Autonomic Function in Paralympic Athletes With Spinal Cord Injury—Reply
Authors: Marco Bernardi, Elena Cavarretta, Antonio Pelliccia
Journal: JAMA Cardiology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
OP0123 SAFETY PROFILE OF JAK-INHIBITORS VERSUS TNF-INHIBITORS IN REAL-WORLD CLINICAL PRACTICE: DATA FROM A MULTICENTER REGISTER
Authors: B. Hernández-Cruz, C. Sánchez-Piedra, M. Freire González, N. Busquets, J. García-González, M. Moreno, J. M. Blanco, S. Manrique Arija, E. Perez-Pampín, F. Sánchez-Alonso, I. Castrejon
Journal: Annals of the Rheumatic Diseases (2021)

Background: JAK-inhibitors (JAKi) are small molecules emerging as a promising treatment for immune mediated diseases. Data from clinical trials are very promising. But long-term observational studies, with patients with diverse clinical backgrounds are required to confirm safety profile. Objectives: To compare the safety profile of JAKi versus TNF antagonists (anti-TNF) in a multicenter real world dataset. Methods: Data of patients enrolled in BIOBADASER 3.0 up to November 2020 with the start of anti-TNF or JAKi were analysed. Adverse events (AE) were classified according to Meddra dictionary (v19.0). For each group, demographic, clinical variables and ncidence rate ratios of AE per 1000 patients-year (PYs) and 95% confidence interval were estimated. Results: A total of 3,729 patients on anti-TNF (5,306) or JAKi (493) were analyzed. Patients on JAKi were older and with a mean disease duration of 10 years. JAKi were prescribed as first line treatment only in 24% of patients. The main reason of stopping treatment was ineffectiveness (53-59%) followed by adverse events (25-34%) in both groups. Survival during first year was similar between groups. Table 1. Patient characteristics and adverse events by treatment group Anti-TNF JAKi Mean age start of treatment (SD), yrs 50.8 (12.6) 57.6 (11.9) Female, n (%) 3122 (58.8) 392 (79.5) Disease duration, median (IQR) 7.0 (2.7-13.7) 9.9 (4.9-16.8) First line biologic, n (%) 2614 (49.3) 117 (23.7) Rheumatoid Arthritis 1385 (41.1) 339 (95.2) Ankylsosing Spondylitis 1031 (30.6) 1 (0.3) Psoriatic Arthritis 957 (28.4) 16 (4.5) DAS28-ESR 4.3 (1.4) 4.7 (1.4) Survival first year (IC 95%) 73.3 (71.9-74.6) 69.7 (66.0-73.0) Charlson Index, mean (SD) 1.9 (1.3) 2.3 (1.6) Reason to stop therapy (n)*: Lack of efficacy 1534 (53.2) 57 (58.8) Adverse event 723 (25.1) 33 (34.0) Adverse events (AE)* Serious infections 14.2 (12.4-16.2) 33.2 (19.3-57.3) Herpes zoster 5.7 (4.6-7.1) 12.8 (5.3-30.7) Tuberculosis 0.7 (0.4-1.3) 0.0 (0.0-0.0) Malignancy/Neoplasia 10.2 (8.7-11.9) 15.3 (6.9-34.2) Cardiac events 13.9 (12.2-16.0) 30.7 (17.4-54.0) GI perforation 1.2 (0.8-1.9) 10.2 (3.8-27.3) Vascular events 9.8 (8.3-11.5) 25.6 (13.8-47.5) *Data show the incidence rate ratio per 1000 patient-years (PYs; 95% CI) Conclusion: Serious infections and herpes zoster tend to be more frequent in patients on JAKi. However patients on JAKi were older, presented higher comorbidity and have a longer disease duration. Disclosure of Interests: None declared
Unlocking G-Quadruplexes as Antiviral Targets
Authors: Ardavan Abiri, Marc Lavigne, Masoud Rezaei, Sanaz Nikzad, Peyman Zare, Jean-Louis Mergny, Hamid-Reza Rahimi, Rhian Touyz
Journal: Pharmacological Reviews (2021)

Guanine-rich DNA and RNA sequences can fold into noncanonical nucleic acid structures called G-quadruplexes (G4s). Since the discovery that these structures may act as scaffolds for the binding of specific ligands, G4s aroused the attention of a growing number of scientists. The versatile roles of G4 structures in viral replication, transcription, and translation suggest direct applications in therapy or diagnostics. G4-interacting molecules (proteins or small molecules) may also affect the balance between latent and lytic phases, and increasing evidence reveals that G4s are implicated in generally suppressing viral processes, such as replication, transcription, translation, or reverse transcription. In this review, we focus on the discovery of G4s in viruses and the role of G4 ligands in the antiviral drug discovery process. After assessing the role of viral G4s, we argue that host G4s participate in immune modulation, viral tumorigenesis, cellular pathways involved in virus maturation, and DNA integration of viral genomes, which can be potentially employed for antiviral therapeutics. Furthermore, we scrutinize the impediments and shortcomings in the process of studying G4 ligands and drug discovery. Finally, some unanswered questions regarding viral G4s are highlighted for prospective future projects. <h3>Significance Statement</h3> G-quadruplexes (G4s) are noncanonical nucleic acid structures that have gained increasing recognition during the last few decades. First identified as relevant targets in oncology, their importance in virology is now increasingly clear. A number of G-quadruplex ligands are known: viral transcription and replication are the main targets of these ligands. Both viral and cellular G4s may be targeted; this review embraces the different aspects of G-quadruplexes in both host and viral contexts.
POS0213 20 Year Follow-Up Of Cardiovascular Event Risk In Rheumatoid Arthritis Compared To Diabetes
Authors: R. Raadsen, R. Agca, A. Voskuyl, M. Boers, W. Lems, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2021)

Background: Patients with rheumatoid arthritis have an increased risk for developing cardiovascular diseases (CVD) compared to the general population, similar to the CVD risk in patients with diabetes mellitus. However, there are no controlled studies investigating the incidence of cardiovascular (CV) events in RA patients with follow up of more than 20 years. Objectives: The objectives of the current study were to investigate the incidence rates of CV events in a long-term follow up cohort of RA patients, and to compare these to a similar cohort representing the general population, ie. The Hoorn study. Methods: The CARRÉ study is an ongoing prospective cohort study, which started in 2001, investigating CV mortality and morbidity in 353 randomly selected patients with RA. Primary endpoints, i.e. verified medical history of coronary, cerebral or peripheral arterial disease, were determined at baseline, and after three, ten, fifteen and twenty years of follow up. Patients were censored at the date of an experienced CV event or their death. Incidence density rates per 100 patient years were calculated. Data were compared to results from the Hoorn study, a Dutch cohort study of glucose metabolism and other CV risk factors that began in 1989. All 2,484 participants were subject to an extensive and repeated CV screening program similar to that used in the CARRÉ study. Results: After 20 years of follow up 118 patients (33%) developed at least one CV event in the Carré group. Mean (SD) follow up time was 11 (6) years with a total of 3,500 years at risk and an incidence rate of 3.4 per 100 patient-years; this is slightly up from the figure reported at 15 years, i.e. 3.2 per 100 patient-years. A CV event-free survival curve is shown in figure 1. After 30 years of follow up, 295 participants of the Hoorn study had developed a CV event, during a mean follow up time 20 (8) years. Total time at risk was 50,000 years, with an incidence rate of 0.6 CV events per 100 patient years. Conclusion: In our cohort the incidence rate of CV events in RA patients has remained consistently high when compared with the general population, despite better control of RA inflammation in recent years. This again confirms the need for timely CVD-risk screening and management. References: [1]Agca R, Hopman L, Laan KJC, van Halm VP, Peters MJL, Smulders YM, et al. Cardiovascular Event Risk in Rheumatoid Arthritis Compared with Type 2 Diabetes: A 15-year Longitudinal Study. J Rheumatol. 2020;47(3):316-24. Figure 1. Survival curve of participants with rheumatoid arthritis. RA = rheumatoid arthritis Disclosure of Interests: None declared
Transthyretin Cardiac Amyloidosis in the Elderly—Tip of a Heart Failure Iceberg?
Authors: Kevin M. Alexander, Sharmila Dorbala
Journal: JAMA Cardiology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Environment‐dependent alterations of immune mediators in urban and rural South African children with atopic dermatitis
Authors: Nonhlanhla Lunjani, Ge Tan, Anita Dreher, Milena Sokolowska, David Groeger, Marcin Warwyzniak, Can Altunbulakli, Patrick Westermann, Wisdom Basera, Lelani Hobane, Maresa Botha, Claudia Gray, Avumile Mankahla, Clive Gray, Kari C. Nadeau, Carol Hlela, Michael Levin, Liam O’Mahony, Cezmi A. Akdis
Journal: Allergy (2021)

In order to improve targeted therapeutic approaches for children with atopic dermatitis (AD), novel insights into the molecular mechanisms and environmental exposures that differentially contribute to disease phenotypes are required. We wished to identify AD immunological endotypes in South African children from rural and urban environments.We measured immunological, socio-economic and environmental factors in healthy children (n = 74) and children with AD (n = 78), in rural and urban settings from the same ethno-linguistic AmaXhosa background in South Africa.Circulating eosinophils, monocytes, TARC, MCP-4, IL-16 and allergen-specific IgE levels were elevated, while IL-17A and IL-23 levels were reduced, in children with AD regardless of their location. Independent of AD, children living in a rural environment had the highest levels of TNFα, TNFβ, IL-1α, IL-6, IL-8, IL-21, MCP-1, MIP-1α, MIP-1β, MDC, sICAM1, sVCAM1, VEGFA, VEGFD and Tie2, suggesting a generalized microinflammation or a pattern of trained immunity without any specific TH polarization. In contrast, IL-15, IL-22, Flt1, PIGF and βFGF were highest in urban children. Rural healthy children had the lowest levels of food allergen-specific IgG4. Early life nutritional factors, medications, animal exposures, indoor environment, sunlight exposure, household size, household income and parental education levels were associated with differences in circulating cytokine levels.This study highlights the immunological impact of environmental exposures and socio-economic status in the manifestation of immune endotypes in children with AD living in urban and rural areas, which are important in selecting appropriately matched immunological therapies for treatment of AD.