tbuckley/cabot-search huggingface dataset:
AB0056 TNFR2 PROMOTES INFLAMMATORY PROGRAMS IN FIBROBLAST-LIKE SYNOVIOCYTES
Authors: T. Suto, K. Von Dalwigk, A. Platzer, B. Niederreiter, T. M. Karonitsch
Journal: Annals of the Rheumatic Diseases (2021)

Background: TNF-mediated fibroblast-like synoviocyte (FLS) activation is important for inflammation and joint destruction in rheumatoid arthritis (RA). The role of TNF-receptor 1 (TNFR1) in FLS activation has thoroughly been characterized. The functions of TNFR2 are, however, largely unknown. Objectives: To investigate the contribution of TNFR2 to the TNF-mediated activation of FLS. Methods: RA-FLS were transfected with TNFR2-targeting siRNA pools and transcriptional changes were determined by RNA-seq. QPCR, ELISA and immunoblotting were used to confirm the RNA-seq results and to gain insights into the pathways that regulate TNFR2-mediated changes in FLS. Results: TNF stimulation of FLS resulted in a strong upregulation of proinflammatory cytokines, chemokines, tissue-degrading enzymes and other genes that are associated with synovial inflammation in RA. Silencing of TNFR2 markedly diminished the TNF-response of RA-FLS. Especially, “interferon”-stimulated-genes (ISGs) including putative master regulators of joint inflammation, such as the CXCR3 chemokines CXCL9, CXCL10 and CXCL11 were affected by the knockdown of TNFR2. Consistently, immunoblots showed that TNFR2 was required for the TNF-induced phosphorylation of the transcription factor STAT1, which is known to mediate the transcription of ISGs, such as CXCR3 chemokines. Conclusion: TNFR2 regulates proinflammatory gene expression in RA-FLS via STAT1 and thereby contributes to the detrimental effects of TNF in synovial joint inflammation. Disclosure of Interests: None declared
Publisher Correction: Altered perivascular fibroblast activity precedes ALS disease onset
Authors: Anna Månberg, Nathan Skene, Folkert Sanders, Marta Trusohamn, Julia Remnestål, Anna Szczepińska, Inci Sevval Aksoylu, Peter Lönnerberg, Lwaki Ebarasi, Stefan Wouters, Manuela Lehmann, Jennie Olofsson, Inti von Gohren Antequera, Aylin Domaniku, Maxim De Schaepdryver, Joke De Vocht, Koen Poesen, Mathias Uhlén, Jasper Anink, Caroline Mijnsbergen, Hermieneke Vergunst-Bosch, Annemarie Hübers, Ulf Kläppe, Elena Rodriguez-Vieitez, Jonathan D. Gilthorpe, Eva Hedlund, Robert A. Harris, Eleonora Aronica, Philip Van Damme, Albert Ludolph, Jan Veldink, Caroline Ingre, Peter Nilsson, Sebastian A. Lewandowski
Journal: Nature Medicine (2021)
Evaluation of Systolic Blood Pressure, Use of Aspirin and Clopidogrel, and Stroke Recurrence in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke Trial
Authors: Adam de Havenon, S. Claiborne Johnston, J. Donald Easton, Anthony S. Kim, Kevin N. Sheth, Maarten Lansberg, David Tirschwell, Eva Mistry, Shadi Yaghi
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Elevated systolic blood pressure (SBP) after acute ischemic stroke and transient ischemic attack (TIA) is associated with future stroke risk. <h3>Objective</h3> To explore the association of dual antiplatelet therapy (DAPT) with stroke recurrence among patients with acute ischemic stroke and TIA with or without elevated baseline SBP. <h3>Design, Setting, and Participants</h3> This cohort study performed a post hoc subgroup analysis of the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which was a multicenter trial conducted from 2010 to 2018 at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand. Patients enrolled in POINT with available blood pressure and outcome data were included in this cohort. Statistical analysis was performed from November 2020 to January 2021. <h3>Exposures</h3> Baseline SBP less than 140 mm Hg vs greater than or equal to 140 mm Hg and the interaction term of SBP (&lt;140 mm Hg vs ≥140 mm Hg) × treatment group (aspirin vs DAPT). <h3>Main Outcomes and Measures</h3> The primary outcome was ischemic stroke during 90 days of follow-up. The statistical analysis fit Cox proportional hazards models adjusted for patient age, race, premorbid hypertension, diabetes, and final diagnosis of the qualifying event (stroke vs TIA). <h3>Results</h3> Among 4781 patients in the cohort, the mean (SD) age was 64.6 (13.1) years; 2142 (44.8%) were male individuals, 3487 (72.9%) were White individuals, and 266 (5.6%) had a primary outcome of ischemic stroke during follow-up. There were 946 patients (19.8%) with baseline SBP less than 140 mm Hg and 3835 (80.2%) with SBP greater than or equal to 140 mm Hg. The interaction term (SBP × treatment) was significant (<i>P </i>for interaction = .03). In the subgroup of patients with SBP less than 140 mm Hg, the hazard ratio (HR) of DAPT vs aspirin alone for ischemic stroke was 0.36 (95% CI, 0.18-0.72;<i>P</i> = .004), whereas the HR in the subgroup with SBP greater than or equal to 140 mm Hg was 0.79 (95% CI, 0.60-1.02;<i>P</i> = .08). When evaluating the outcome of ischemic stroke within 7 days of randomization, the interaction term was significant (<i>P </i>for interaction = .02), and the HR for patients with DAPT with SBP less than 140 mm Hg was 0.19 (95% CI, 0.07-0.55;<i>P</i> = .002). <h3>Conclusions and Relevance</h3> In the POINT trial, patients with SBP less than 140 mm Hg at presentation received a greater benefit from 90 days of DAPT than those with higher baseline SBP, particularly for reduction of early ischemic stroke recurrence. Additional research is needed to replicate these findings and potentially test whether mild SBP reduction and DAPT within 12 hours of stroke onset lowers early risk of stroke recurrence.
Use of diuretics and outcomes in patients with type 2 diabetes: findings from the <scp>EMPA‐REG OUTCOME</scp> trial
Authors: Pierpaolo Pellicori, David Fitchett, Mikhail N. Kosiborod, Anne P. Ofstad, Leo Seman, Bernard Zinman, Isabella Zwiener, Christoph Wanner, Jyothis George, Silvio E. Inzucchi, Jeffrey M. Testani, John G.F. Cleland
Journal: European Journal of Heart Failure (2021)

Abstract Aims Loop diuretics (LD) relieve symptoms and signs of congestion due to heart failure (HF), but many patients prescribed LD do not have such a diagnosis. We studied the relationship between HF diagnosis, use of LD, and outcomes in patients with type 2 diabetes mellitus (T2DM) enrolled in the EMPA‐REG OUTCOME trial. Methods and results The relationship between HF diagnosis, use of LD, and outcomes was evaluated in four patient subgroups with T2DM: (i) investigator‐reported HF on LD, (ii) investigator‐reported HF not on LD, (iii) no HF on LD, and (iv) no HF and not on LD, and we assessed their risk of cardiovascular events. Of 7020 participants, 706 (10%) had a diagnosis of HF at baseline, of whom 334 were prescribed LD. However, 755 (11%) patients who did not have a diagnosis of HF were prescribed LD. Compared to those with neither HF nor prescribed LD (reference group; placebo), those with both HF and receiving LD had the highest rates for all‐cause [hazard ratio (HR) (95% confidence interval) 3.19 (2.03–5.01)] and cardiovascular mortality [3.83 [(2.28–6.44)], and HF hospitalizations [9.51 (5.61–16.14)]. Patients without HF but prescribed LD had higher rates for all three outcomes [1.62 (1.10–2.39); 1.97 (1.26–3.08); 3.20 (1.90–5.39)], which were similar to patients with HF who were not receiving LD [1.42 (0.78–2.57); 1.56 (0.78–3.11); 3.00 (1.40–6.40)]. Empagliflozin had similar benefits regardless of subgroup ( P for interaction &gt;0.1 for all outcomes). Conclusion Patients with T2DM prescribed LD are at greater risk of cardiovascular events even if they are not reported to have HF; this might reflect under‐diagnosis. Empagliflozin was similarly effective in all subgroups investigated.
Abstract 15669: Etiologies and Risk Factors for 30-Day Readmissions in Patients Who Underwent Chronic Total Occlusion Percutaneous Coronary Intervention. Nationwide Analysis Using the National Readmission Database
Authors: Alejandro Lemor, Chirag Bavishi, Carlos A Gongora, Seyed Hamed Hosseinidehkordi, Farid Gholitabar, Syed A Ahsan, Ramesh M Gowda
Journal: Circulation (2017)

Background: The use of chronic total occlusion percutaneous coronary intervention (CTO PCI) has increased in the past years, with better success and lower complication rates. We sought to determine...
Effectiveness of Tocilizumab in Patients Hospitalized With COVID-19
Authors: Xavier Mariette, Olivier Hermine, Pierre-Louis Tharaux, Matthieu Resche-Rigon, Philippe Gabriel Steg, Raphaël Porcher, Philippe Ravaud
Journal: JAMA Internal Medicine (2021)

This follow-up study of the CORIMUNO-TOCI-1 randomized clinical trial examines the association between survival and C-reactive protein levels in patients hospitalized with COVID-19 who were treated with tocilizumab.
Help me trust you after my misdiagnosis
Authors: Sarah Clark
Journal: BMJ (2021)

Help me trust you after my misdiagnosisSarah Clark shares what it is like to experience a misdiagnosis and how health professionals can support someone who has been misdiagnosed Sarah Clark Debilitating daily lifeFor more than 12 years I lived with undiagnosed chronic pain, spinal problems, pelvic floor dysfunction, gastrointestinal issues, bladder problems, bleeding tendency, and easy scarring, among other symptoms.I was exhausted.Living with all these problems in combination made my daily life debilitating and challenging on a practical level.But even more difficult was not being believed about my physical problems by health professionals.
Correspondence on ‘Immunogenicity and safety of anti-SARS-Cov-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort’
Authors: Chiara Salviani, Francesco Scolari, Federico Alberici
Journal: Annals of the Rheumatic Diseases (2021)

Table 1 Antibody response to SARS-CoV-2 infection in AAV patients Reference Age Sex Diagnosis Time from last RTX (days) B cell count (cells/mm 3 ) Hypogammaglobulinaemia Anti-SARS-CoV-2 IgG 4 73 F GPA 45 0 Yes Negative 4 74 F MPA 100 0 No Low level (39 AU/mL, cut-off >10)
AB0575 FACTORS ASSOCIATED WITH PSORIATIC ARTHRITIS ACTIVITY IN CLINICAL PRACTICE
Authors: Y. Korsakova, E. Loginova, T. Korotaeva, E. Gubar, S. Glukhova, E. Vasilenko, A. Vasilenko, N. Kuznetsova, I. Patrikeeva, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic Arthritis (PsA) is a multifaceted disease with various clinical domains. A number of composite indices has been developed recently [1, 2]. DAPSA ( D isease A ctivity in PS oriatic A rthritis) is the valid instrument for assessment of PsA activity focused on peripheral arthritis. But other factors can influence on PsA activity and haven’t studied yet. Objectives: to identify factors that are associated with PsA activity based on the data from RU-PsART cohort. Methods: 117 (M/F=63(54%)/54(46%)) patients (pts) with active PsA fulfilling the CASPAR criteria mean age 44.3 ± 10.9 yrs, mean DAPSA 37.8±21.4, mean PsA duration 73.4±78.4 mo, mean PsO duration 213.4±152.5 mo, were included. Data was collected from 43 rheumatology centers of the Russian Federation. All pts underwent standard clinical examination of PsA activity at enrollment. DAPSA, ESR (mm/h), CRP (mg/L), dactylitis, enthesitis by LEI plus Plantar Fascia, BSA (%), HAQ-DI and fatigue by Fatigue Scale (V.4) FACIT (Functional Assessment of Chronic Illness Therapy), BMI (kg/m 2 ) were evaluated. DAPSA &gt; 28 indicate high activity. Multi-dimensional step-by-step discriminant analysis was used to identify a group of features that are associated with high PsA activity by DAPSA. M±SD, %, OR 95% (CI) were performed. Results: The following features proved to be the most informative: LEI (p=0.739), tenderness of the Plantar Fascia (p=0.003), age (p=0.0004), FACIT (p=0.092), PsA duration &gt;2 yrs (p=0.013), BSA&gt;3% (p=0.021), Nail PsO (p=0.092), BMI (kg/m 2 ) (p=0.22). The area under the ROC-curve (AUC) 0.768, 95% CI (0.624-0.913). Sensitivity/ Specificity of model 77.0%/ 69% accordingly (Figure 1). Figure 1 ROC analysis of the Sensitivity and Specificity of the model. Conclusion: Weight, enthesitis, skin and nail PsO severity, fatigue and PsA duration &gt;2 yrs are associated with high PsA activity as well as articular symptoms. New combination indices based on these features should be developed and validated in clinical practice. References: [1]Helliwell P, et al. The development of candidate composite disease activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis. 2013; 72: 986-91. doi: 10.1136/annrheumdis-2012-201341. [2]Salaffi F, et al. Disease Activity in Psoriatic Arthritis: Comparison of the Discriminative Capacity and Construct Validity of Six Composite Indices in a Real World. BoiMed Res Int 2014; 2014:52805 http://dx.doi.org/10.1155/2014/528105 Disclosure of Interests: None declared.
Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies
Authors: Suowen Xu, Iqra Ilyas, Peter J. Little, Hong Li, Danielle Kamato, Xueying Zheng, Sihui Luo, Zhuoming Li, Peiqing Liu, Jihong Han, Ian C. Harding, Eno E. Ebong, Scott J. Cameron, Alastair G. Stewart, Jianping Weng
Journal: Pharmacological Reviews (2021)

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1<i>β</i> monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. <h3>Significance Statement</h3> The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.
Recent Progress in Development of Wearable Pressure Sensors Derived from Biological Materials
Authors: Hong Pan, Tae‐Woo Lee
Journal: Advanced Healthcare Materials (2021)

Abstract This review summarizes recent progress in the use of biological materials (biomaterials) in wearable pressure sensors. Biomaterials are abundant, sustainable, biocompatible, and biodegradable. Especially, many have sophisticated hierarchical structure and biological characteristics, which are attractive candidates for facile and ecologically‐benign fabrication of wearable pressure sensors that are biocompatible, biodegradable, and highly sensitivity. The biomaterials and structures that use them in wearable pressure sensors that exploit sensing mechanisms such as piezoelectric, triboelectric, piezoresistive and capacitive effects are present. Finally, remaining impediments are discussed to use of biomaterials in wearable pressure sensors.
AB0680 SARCOPENIA RATE IN COVID-19 SURVIVORS
Authors: D. Levy, M. Giannini, W. Oulehri, M. Riou, C. Marcot, A. Meyer, B. Geny
Journal: Annals of the Rheumatic Diseases (2021)

Background: COVID-19 survivors may have high risks of developing sarcopenia, which is associated to handicap, poor quality of life, higher healthcare costs, increased risk of falls, increased mortality (1). Objectives: To assess sarcopenia rate (which has not been described yet) following COVID-19 hospitalization and to highlights features associated with sarcopenic vs. non-sarcopenic patients. Methods: Major confirmed COVID-19 patients undergoing intensive care unit (ICU) or Pneumology Department admission in Strasbourg University Hospital between March and June 2020 were prospectively included. Muscle and cardio-respiratory evaluations were performed 3 months after discharge. Sarcopenic patients were compared to non-sarcopenic ones. A second muscle assessment 6 months after discharge was performed in patients with pathologic muscle tests. Results: 127 patients were included, 39 (30.7%) not requiring ICU care, 88 (69.3%) requiring ICU care. The cohort consisted of 71% male patients, with a median age of 63 years [28-82]. Forty-one-percent were obese (BMI&gt;30 kg/m 2 ). Most individuals had preexisting comorbidities (82 patients, 70%), mainly hypertension and diabetes mellitus. The median total hospital stay duration was 22 days and up to 89 days. At the 3 months assessment, 17/127 (13%) patients were diagnosed with sarcopenia which comprised 6/17 (35%) severe sarcopenia (4.7% of the total cohort). At the 6 months assessment, only 4/15 (27%) of the initial sarcopenic patients remained sarcopenic (3% of the total cohort) and 3 of these 4 patients had severe sarcopenia. BMI (26,3 vs. 29,3, p =0.03), COPD (20% vs. 3%, p= 0.03), comorbidities (93% vs. 67%, p =0.04), total hospital stay duration (33 vs. 20 days, p =0.03) and ICU stay duration (33 vs. 13 days, p =0.01) were significantly associated with sarcopenic vs. no sarcopenic patients. However, there was no significant difference concerning cardio-pulmonary evaluations between these two groups. Conclusion: We here highlighted a sarcopenia prevalence at 3 and 6 months following a hospitalization for COVID-19 of 13% and 3% respectively, occurring mainly in patients with comorbidities. Sarcopenia was not associated to worse cardio-pulmonary results in comparison with non-sarcopenic patients. References: [1]Di Filippo L, De Lorenzo R, D’Amico M, Sofia V, Roveri L, Mele R, et al. COVID-19 is associated with clinically significant weight loss and risk of malnutrition, independent of hospitalisation: A post-hoc analysis of a prospective cohort study. Clinical Nutrition [Internet]. oct 2020. https://linkinghub.elsevier.com/retrieve/pii/S0261561420305896 Disclosure of Interests: None declared
Regulation of the Methylation and Expression Levels of the BMPR2 Gene by SIN3a as a Novel Therapeutic Mechanism in Pulmonary Arterial Hypertension
Authors: Malik Bisserier, Prabhu Mathiyalagan, Shihong Zhang, Firas Elmastour, Peter Dorfmüller, Marc Humbert, Gregory David, Sima Tarzami, Thomas Weber, Frederic Perros, Yassine Sassi, Susmita Sahoo, Lahouaria Hadri
Journal: Circulation (2021)

Epigenetic mechanisms are critical in the pathogenesis of pulmonary arterial hypertension (PAH). Previous studies have suggested that hypermethylation of the BMPR2 (bone morphogenetic protein receptor type 2) promoter is associated with BMPR2 downregulation and progression of PAH. Here, we investigated for the first time the role of SIN3a (switch-independent 3a), a transcriptional regulator, in the epigenetic mechanisms underlying hypermethylation of BMPR2 in the pathogenesis of PAH.We used lung samples from PAH patients and non-PAH controls, preclinical mouse and rat PAH models, and human pulmonary arterial smooth muscle cells. Expression of SIN3a was modulated using a lentiviral vector or a siRNA in vitro and a specific adeno-associated virus serotype 1 or a lentivirus encoding for human SIN3a in vivo.SIN3a is a known transcriptional regulator; however, its role in cardiovascular diseases, especially PAH, is unknown. It is interesting that we detected a dysregulation of SIN3 expression in patients and in rodent models, which is strongly associated with decreased BMPR2 expression. SIN3a is known to regulate epigenetic changes. Therefore, we tested its role in the regulation of BMPR2 and found that BMPR2 is regulated by SIN3a. It is interesting that SIN3a overexpression inhibited human pulmonary arterial smooth muscle cells proliferation and upregulated BMPR2 expression by preventing the methylation of the BMPR2 promoter region. RNA-sequencing analysis suggested that SIN3a downregulated the expression of DNA and histone methyltransferases such as DNMT1 (DNA methyltransferase 1) and EZH2 (enhancer of zeste 2 polycomb repressive complex 2) while promoting the expression of the DNA demethylase TET1 (ten-eleven translocation methylcytosine dioxygenase 1). Mechanistically, SIN3a promoted BMPR2 expression by decreasing CTCF (CCCTC-binding factor) binding to the BMPR2 promoter. Last, we identified intratracheal delivery of adeno-associated virus serotype human SIN3a to be a beneficial therapeutic approach in PAH by attenuating pulmonary vascular and right ventricle remodeling, decreasing right ventricle systolic pressure and mean pulmonary arterial pressure, and restoring BMPR2 expression in rodent models of PAH.All together, our study unveiled the protective and beneficial role of SIN3a in pulmonary hypertension. We also identified a novel and distinct molecular mechanism by which SIN3a regulates BMPR2 in human pulmonary arterial smooth muscle cells. Our study also identified lung-targeted SIN3a gene therapy using adeno-associated virus serotype 1 as a new promising therapeutic strategy for treating patients with PAH.
Near‐Infrared Light‐Regulated Drug‐Food Homologous Bioactive Molecules and Photothermal Collaborative Precise Antibacterial Therapy Nanoplatform with Controlled Release Property
Authors: Xinyu Sun, Lihua Li, Hui Zhang, Mengna Dong, Jiao Wang, Pei Jia, Tong Bu, Xin Wang, Li Wang
Journal: Advanced Healthcare Materials (2021)

Herein, a collaborative precise antibacterial wound healing therapy nanoplatform integrating drug-food homologous bioactive molecule (cinnamaldehyde, CA) with photothermal therapy (PTT) is presented. Copper-gallic acids-cinnamaldehyde-polydopamine nanorods (Cu-GA-CA-PDA NRs) with near-infrared light (NIR)-controlled CA release property are fabricated, which also integrate CA and photothermal synergistic sterilization, as well as antioxidant, anti-inflammatory, and anti-infection capacities. The characteristics of NIR-mediated CA release and photothermal response of Cu-GA-CA-PDA NRs support their excellent sterilization performance in vitro/in vivo. In addition, under the guidance of NIR, Cu-GA-CA-PDA NRs can hinder the formation of inflammatory cells, reduce oxidative stress damage, accelerate the regeneration of skin tissues in S. aureus-infected wound sites, and achieve the goal of promoting wound healing. Therefore, NIR-mediated Cu-GA-CA-PDA NRs with multifunctional biological activities provide a highly competitive strategy for curing bacteria-infected wounds.