tbuckley/cabot-search huggingface dataset:
AB0443 BIOMARKER SUCH AS IL-17, IL-21 AND TIMP-1, IS USEFUL FOR PREDICTING THE PATHOPHYSIOLOGY OF CONNECTIVE TISSUE DISEASE-ASSOCIATED PULMONARY HYPERTENSION
Authors: S. Nakashima, T. Kameda, H. Shimada, M. Mahmoud Fahmy Mansour, R. Wakiya, M. Kato, Y. Ushio, K. Sugihara, H. Dobashi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Connective tissue disease-associated pulmonary hypertension (CTD-PH) is constructed by a variety of pathologies, including cardiac, pulmonary, and vascular involvement, as well as immune abnormalities. Because of its various constructs, it is difficult for many respiratory physicians, cardiologists, and rheumatologists to determine a treatment strategy for CTD-PH. In addition, CTD-PH has different pathologies from iPAH, and there are cases in which immunosuppressive therapy is effective. These suggests that the two PAHs may have different pathogenesis, including inflammation in the pulmonary artery. However, there are not enough biomarkers to distinguish pathologies. On the other hand, it has been reported that various cytokines such as TIMP-1, Interleukin (IL)-6, IL-17, and IL-21 are involved in the pathogenesis of CTD-PH or vasculitis. (1,2) However, the relationship between these cytokine expression and the pathogenesis or treatment of CTD-PH has not been fully clarified. Objectives: To clarify the relationship between cytokine profile and clinical features, change in cytokines and hemodynamics by treatment, association with the effectiveness of immunosuppressive therapy. Methods: Patients suspected PH was included. At the time of cardiac catheterization(RHC), sera in pulmonary pre and post-capillary were collected and TIMP-1, MCP-1, IL-17 and IL-21, IL-12p70 and IL-6 were analyzed by ELISA(ABCAM UK, Ella simple plex USA). The following clinical data were collected: age, gender, underlying disease, complication of interstitial lung disease, treatment (immunosuppressant and pulmonary vasodilator), hemodynamics. Furthermore, we investigated the relationship between cytokines and clinical data. Results: 15 cases of CTD-PH, 13 cases of non-CTD-PH, and 6 cases of non-PH were analyzed. (SSc 12 cases, MCTD 7cases, SLE 2 cases, and others 13 cases) 28 cases were diagnosed with PH by RHC. There was a positive correlation between IL-6 and mean pulmonary arterial pressure in all PH case. In addition, MCP-1, IL-6, and TIMP-1 tend to be high in SSc-PH cases. On the other hand, in Non-SSc-PH, IL-12p70 and IL-17 were high. In cases who pulmonary vascular hemodynamics improved by treatment, IL-17, IL-21, and TIMP-1 decreased. Conclusion: Biomarker profiles in pulmonary capillaries may differ depending on the disease. Furthermore, it suggested that IL-17, IL-21 and TIMP-1 may be biomarkers of therapeutic effect. References: [1]Hashimoto-Kataoka T. et al. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2677-86. [2]Jun Ishizaki et al. Arthritis Res Ther. 2017 Sep 29;19(1):218. Disclosure of Interests: None declared.
AB0240 PREDICTORS OF RESPONSE TO BIOLOGIC AGENTS IN RHEUMATOID ARTHRITIS
Authors: K. Saadaoui, H. Sahli, S. Jemmali, S. Boussaid, S. Rekik, E. Cheour, M. Elleuch
Journal: Annals of the Rheumatic Diseases (2021)

Background: In rheumatoid arthritis (RA), the ‘treat-to-target’ therapeutic approach imposes rigorous control of disease activity. Although biological agents have been shown to be effective, these therapies fail sometimes to achieve therapeutic goals. Objectives: In this study we tried to determine predictive factors of good therapeutic response to biologic disease-modifying antirheumatic drugs (bDMARD). Methods: This is a retrospective study including 374 Tunisian patients who received their first biotherapy between 2014 and 2016. Categorical variables were reported in numbers and percentages, while quantitative variables were expressed by mean with standard deviations. The univariate analysis was performed using the student t-test or the Chi2 test. Multivariate analysis was performed by binary logistic regression. Results: Average age of our cohort was 55 ± 12.5 years with a female predominance of 87.2%. The average duration of RA was 11.7 ± 6.7 years. Rheumatoid factors were positive in 79% and ACPA were positive in 72% of cases. After the introduction of biotherapy, low disease activity (LDA) or remission was achieved in 55% of cases (206 patients). No statistically significant difference between biotherapy responder and non-responder groups for age (55.7 vs. 54.7 years; p = 0.44), gender (Female: 86.5% vs. 88.7%; p = 0.08) and disease duration (12 years vs. 11.4 years; p = 0.41). A significant difference between the two groups was found for the positivity of rheumatoid factors (76.4% vs. 88.9%; p = 0.004), methotrexate’s association (65% vs. 53.4%; p = 0.02) and corticosteroids’ use (50% vs. 66.5%; p &lt; 0.001). Positive predictive factors of remission or LDA by biotherapy were female sex (Odds Ratio = 2.2; p = 0.026), presence of rheumatoid factors (Odds Ratio = 2.64; p = 0.001), association with methotrexate (Odds Ratio = 1.69; p = 0.028). Whereas, corticosteroid use (OR = 0.41; p &lt; 10-3) was a negative predictor of disease control by bDMARDs. Conclusion: Achieving LDA low level or even remission is currently achievable with biological treatments. Certain factors need to be studied in order to optimize RA treatment and adapt the right bDMARD for each patient. Disclosure of Interests: None declared
Broad Concordance in the Spatial Distribution of Adaptive and Neutral Genetic Variation across an Elevational Gradient in Deer Mice
Authors: Rena M Schweizer, Matthew R Jones, Gideon S Bradburd, Jay F Storz, Nathan R Senner, Cole Wolf, Zachary A Cheviron
Journal: Molecular Biology and Evolution (2021)

When species are continuously distributed across environmental gradients, the relative strength of selection and gene flow shape spatial patterns of genetic variation, potentially leading to variable levels of differentiation across loci. Determining whether adaptive genetic variation tends to be structured differently than neutral variation along environmental gradients is an open and important question in evolutionary genetics. We performed exome-wide population genomic analysis on deer mice sampled along an elevational gradient of nearly 4,000 m of vertical relief. Using a combination of selection scans, genotype-environment associations, and geographic cline analyses, we found that a large proportion of the exome has experienced a history of altitude-related selection. Elevational clines for nearly 30% of these putatively adaptive loci were shifted significantly up- or downslope of clines for loci that did not bear similar signatures of selection. Many of these selection targets can be plausibly linked to known phenotypic differences between highland and lowland deer mice, although the vast majority of these candidates have not been reported in other studies of highland taxa. Together, these results suggest new hypotheses about the genetic basis of physiological adaptation to high altitude, and the spatial distribution of adaptive genetic variation along environmental gradients.
Diagnostic challenges and pockets of susceptibility identified during a measles outbreak, Luxembourg, 2019
Authors: Michel Kohnen, Patrick Hoffmann, Caroline Frisch, Emilie Charpentier, Aurélie Sausy, Judith M Hübschen
Journal: Eurosurveillance (2021)

Luxembourg was among the first countries in the World Health Organization (WHO) European Region documenting interruption of endemic measles transmission, but an increased incidence was registered in spring 2019. The outbreak started with an unvaccinated student who had been to a winter sports resort in a neighbouring country, where a measles outbreak was ongoing. Subsequently, 12 secondary and two tertiary cases were confirmed among students from the same school, relatives and healthcare workers, as well as six probably unrelated cases. Only 11 cases initially fulfilled the WHO definition for suspected measles cases. Fourteen of 20 cases with information on country of birth and the majority of unvaccinated cases (10/12) were born outside of Luxembourg. Measles IgM antibody results were available for 16 of the confirmed cases, and five of the eight IgM negative cases had been vaccinated at least once. All 21 cases were PCR positive, but for three previously vaccinated cases with multiple specimen types, at least one of these samples was negative. The outbreak highlighted diagnostic challenges from clinical and laboratory perspectives in a measles elimination setting and showed that people born abroad and commuters may represent important pockets of susceptible people in Luxembourg.
Targeting the CCR6/CCL20 Axis in Entheseal and Cutaneous Inflammation
Authors: Zhenrui Shi, Emma Garcia‐Melchor, Xuesong Wu, Anthony E. Getschman, Mimi Nguyen, Douglas J. Rowland, Machelle Wilson, Flavia Sunzini, Moeed Akbar, Mindy Huynh, Timothy Law, Smriti K. Raychaudhuri, Siba P. Raychaudhuri, Brian F. Volkman, Neal L. Millar, Sam T. Hwang
Journal: Arthritis & Rheumatology (2021)

To assess the involvement of the CCR6/CCL20 axis in psoriatic arthritis (PsA) and psoriasis (PsO) and to evaluate its potential as a therapeutic target.First, we quantified CCL20 levels in peripheral blood and synovial fluid from PsA patients and examined the presence of CCR6+ cells in synovial and tendon tissue. Utilizing an interleukin-23 minicircle DNA (IL-23 MC) mouse model exhibiting key features of both PsO and PsA, we investigated CCR6 and CCL20 expression as well as the preventive and therapeutic effect of CCL20 blockade. Healthy tendon stromal cells were stimulated in vitro with IL-1β to assess the production of CCL20 by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of conditioned media from stimulated tenocytes in inducing T cell migration was interrogated using a Transwell system.We observed an up-regulation of both CCR6 and CCL20 in the enthesis of IL-23 MC-treated mice, which was confirmed in human biopsy specimens. Specific targeting of the CCR6/CCL20 axis with a CCL20 locked dimer (CCL20LD) blocked entheseal inflammation, leading to profound reductions in clinical and proinflammatory markers in the joints and skin of IL-23 MC-treated mice. The stromal compartment in the tendon was the main source of CCL20 in this model and, accordingly, in vitro activated human tendon cells were able to produce this chemokine and to induce CCR6+ T cell migration, the latter of which could be blocked by CCL20LD.Our study highlights the pathogenic role of the CCR6/CCL20 axis in enthesitis and introduces the prospect of a novel therapeutic approach for treating patients with PsO and PsA.
POS1285 FOOT DISORDERS AND FALLS RISK IN OLDER PERSONS
Authors: N. Fani, E. Toulgui, D. Khalifa, S. Mtaoua, W. Ouanes, S. Jemni
Journal: Annals of the Rheumatic Diseases (2021)

Background: Falls are major problems in older people, leading to serious morbidity and mortality. Many studies have identified intrinsic and extrinsic fall risk factors in order to develop preventive strategies and guidelines. There are few reports which studied the impacts of aging feet on falls [1]. Objectives: The present study aimed to explore foot musculoskeletal disorders and their relationship to falls in a healthy aging population. Methods: This was a cross-sectional descriptive study involving the patients aged 65 years and over who were independent in self-care and walking followed at the physical medicine and rehabilitation department of the university hospital of sousse over 3 months. The analysed data focused on the epidemiological and clinical characteristics.Trained physicians evaluated health status, foot problems, and fall(s) history of all subjects. Walking performance was assessed using the ‘Timed Get Up &amp; Go’ test and the unipedal stance test was used for the assessment of balance. Footprints were taken from the standing position. Associated factors of foot disorders and falls were analyzed. Results: There were 45 subjects: 18 men, 27 women with a mean age of 69.6 [65-86] years. Foot deformities presented in 87% and were a significantly associated with walking performance or falls (p=0.01, p=0.02). The most common foot musculoskeletal disorder were Halux valgus 31%, followed by Mallet toe 15%. Arch of foot classified by physical examination revealed that pes planus was presented in 35% of cases. There was a significant correlation between BMI and an arch index (p=0.04). Foot problems remained significantly associated with impaired timed up and go test and the unipedal stance test. The causes of pain were plantar fasciitis, hallux valgus, callus, metatarsalgia, and inappropriate footwear. Falls were reported in 33.3 of patients. Falls were significantly associated with Hallux valgus, mallet toe and pain (p&lt;0.05). Conclusion: Independent of the influence of age, gender, common conditions; foot problems have a significant impact on the ability to perform functional tasks integral to independent living. References: [1]Menz HB, Lord SR: Foot problems, functional impairment, and falls in older people. J Am Podiatr Med Assoc 1999;89:458– 467. 3 Americ Disclosure of Interests: None declared
Socioeconomic and Racial Inequities in Breast Cancer Screening During the COVID-19 Pandemic in Washington State
Authors: Ofer Amram, Jeanne Robison, Solmaz Amiri, Bethann Pflugeisen, John Roll, Pablo Monsivais
Journal: JAMA Network Open (2021)

Data included completed screening mammograms within a large statewide nonprofit community health care system in Washington State between April 1, 2018, and December 31, 2020.This health care system included more than 230 primary care, specialty care, and urgent care clinics, and 8 hospitals across Washington State.The MultiCare institutional review board approved this study protocol and granted waivers of individual consent based on removal of individually identifying data.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Measures and Statistical AnalysisSociodemographic data included patients' race and ethnicity, insurance, and zip code of residence.Rural-urban commuting area codes differentiated between urban vs rural residence.Inclusion criteria included women who had at least 1 screening mammogram within the health system in 2018 or 2019.Frequency analysis and χ 2 tests were performed using a significance level of P < .05 to test for differences in screening in 2019 and 2020.Testing was 2-sided.Statistical analysis was performed using R statistical software version 4.03 (R Project for Statistical Computing). ResultsAmong the 55 678 screenings in April to December 2019, 45 572 patients were non-Hispanic White (81.8%),54 620 patients lived in urban areas (98.1%), and 22 761 patients were commercially insured (40.9%); the mean (SD) age was 62.0 (11.3) years.From 2019 to the same period in 2020, there was a 49% decrease in screenings (55 678 screenings in 2019 vs 27 522 screenings in 2020), with some differences apparent in the demographic characteristics between the 2 years (Table ).We observed greater and significant reductions in the number of screenings from 2019 to 2020 for women who were Hispanic (1727 vs 619; -64.2%),American Indian/Alaska Native (215 vs 84; -60.9%), mixed race
AB0501 CORRELATION BETWEEN AXIAL AND PERIPHERAL ENTHESIS IN SPONDYLARTHRITIS
Authors: H. Ferjani, M. Yasmine, K. Maatallah, E. Labbene, H. Riahi, D. Kaffel, M. Bouaziz, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Enthesitis is the clinical hallmark of spondylarthritis. It refers to the inflammation of joint attach in the bone. Several sites enthesitis may be affected, and a wide variety of scoring systems were available. Objectives: We aimed to determine the prevalence of axial enthesitis in the anterior chest wall (ACW), and its correlation with peripheral sites especially, the Achilles tendon (AT). Methods: We conducted a prospective study including patients with SpA according to the ASAS criteria. Sociodemographic data, as well as disease characteristics, were recorded. The Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was used to assess clinical entheses (first and seventh costochondral joints, posterior superior iliac spine, anterior superior iliac spine, iliac crest, and Achilles tendon insertion). The presence of enthesitis on the US was then assessed in the right and left sternoclavicular (SCJ), manubriosternal (MSJ) joints, as well as in the AT, using Esaote My Lab 50. Results: The study included 47 patients with SpA: axial (n=26), axial and peripheral (n=21). There was a female predominance (sex ratio: 0.2). The mean age was 42.2 years ± 12.6 [11-70]. The age of onset of the disease was &lt;40 years in 59.6% of cases. Tenderness in entheseal sites was found in 63.8% of patients, especially in the plantar fascia and AT (32.7%, 6%, respectively). The mean MASES score was 2.9 [0-13]. Clinical ACW involvement (29.1%) was at follows: 1st right chondro-sternal joint (CSJ) (19.1%), 1st left CSJ (25.5%), 7th right CSJ (27.7%) and 7th left CSJ (31.9%).US involvement of the ACW was 14.3%. Enthesitis of the AT was found in 70% of cases on US examination. ACW US involvement was correlated neither to the BMI nor to MASES score (p=0.16, p=0.6 respectively). Similarly, there was no correlation between the presence of US ACW enthesitis and clinical nor the US AT enthesitis (p=0.09, p=0.209, respectively). Conclusion: Our study showed that ACW enthesitis is frequent in SpA, especially by US screening. This axial enthesitis, don’t necessarily reflect a simultaneous clinical or US involvement of the peripheral entheses. Further studies are needed to characterize this subtype of SpA. References: [1]Verhoeven F, Guillot X, Godfrin-Valnet M, Prati C, Wendling D. Ultrasonographic evaluation of the anterior chest wall in spondyloarthritis: a prospective and controlled study. J Rheumatol. 2015;42(1):87-92 Disclosure of Interests: None declared.
Salvage Robot-assisted Renal Surgery for Local Recurrence After Surgical Resection or Renal Mass Ablation: Classification, Techniques, and Clinical Outcomes
Authors: Alberto Martini, Filippo Turri, Ravi Barod, Bernardo Rocco, Umberto Capitanio, Alberto Briganti, Francesco Montorsi, Alexandre Mottrie, Ben Challacombe, Brunolf W. Lagerveld, Karim Bensalah, Ronney Abaza, Ketan K. Badani, Reza Mehrazin, Maurizio Buscarini, Alessandro Larcher, Kennedy Okhawere, Oscar E. Martinez, Zine-Eddine Khene, Rai Sonpreet, Nicholas Campain, Ruben De Groote, Paolo Dell’Oglio, Nikos Grivas, Sanchia Goonewardene, Ashok Hemal, Juan Gomez Rivas
Journal: European Urology (2021)
AB0162 OCULAR MANIFESTATIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: D. Monova, S. Monov, R. Shumnalieva, D. Dimova, M. Sotirova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease and is associated with a number of extra-articular organ manifestations, including ocular complications. Objectives: The aim of this study is to evaluate the frequency and characteristics of ocular manifestation in patients with rheumatoid arthritis (RA). Methods: The study involved 87 patients with RA. All the study subjects underwent complete ophthalmological examination involving visual acuity assessment, examination of anterior and posterior eye segments, Schirmer’s test, diameter and mobility of pupils, as well as eyeball mobility assessment of intraocular pressure. Data regarding age, gender, disease duration, age at diagnosis, systemic corticosteroid use, blood pressure, ocular symptoms and detailed ophthalmic history were recorded. The presence of rheumatoid factor in serum was evaluated by standard test methods based on principle of agglutination. All patients were seropositive. Results: 87 patients (26 male, 59 female, mean age 45,6 ± 13,1 years; mean disease duration 7,4 ± 6,2 years) with RA were enrolled in this study. 31 (35,63 %) of them had no ocular symptoms. Among the patients with ocular symptoms, 39 (69,64 %) complained of decreased vision, 33 (58,93 %) - of dry eye, 32 (57,14 %) - of burning, 29 (51,78 %) -photophobia, 28 (50 %) - of gritty sensation, 27 (48,21 %) - of itching, 18 (32,14 %) - of redness, 13 (23,21 %) - of ocular pain, 3 (5,36 %) - of floaters. Ophthalmological examination revealed higher incidence of the following abnormalities in the study group: myopic astigmatism - in 10 (5,74 %) eyes, vascular abnormalities within fundus - in 22 (12,64 %) eyes, increased intraocular pressure (&gt; 21 mm Hg) - in 11 (6,32 %) eyes. Mean IOP values were 17,34 ± 5,12 mm Hg. In 48 eyes Schirmer’s test results were below 10 mm, and in 18 eyes - below 5 mm. Keratoconjunctivitis sicca was present in 31 (35,63 %) of all patients. Episcleritis was diagnosed in 4 patients (4,6 %), scleritis – in 3 (3,45 %). Retinal vasculitis was present in 2 (2,3 %) patients and involves veins and arteries peripheral branches. Lens opacity was found in 13 (14,94 %) patients (21 eyes), mostly in the form of posterior subcapsular cataract (in 16 eyes) and nuclear cataract (in 5 eyes). The mean age of patients with cataracts was 52,3 ± 14,2 years. 13 of the patients with cataracts were either currently taking or had previously taken systemic corticosteroids. Conclusion: In patients with RA numerous abnormalities within the vision of organ may be found. Ocular symptoms are relatively common complications of RA, and may result in irreversible changes in the organ of vision. Regular ophthalmological examinations are essential among the patients with RA. Disclosure of Interests: None declared
Biodegradable Copper‐Based Nanoparticles Augmented Chemodynamic Therapy through Deep Penetration and Suppressing Antioxidant Activity in Tumors
Authors: Runxiao Zheng, Yan Cheng, Fan Qi, Yunyun Wu, Xiaoqing Han, Jiao Yan, Haiyuan Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Chemodynamic therapy (CDT) efficacy has been limited by the poor penetration ability of large nanoparticles (NPs) and the antioxidant activity of tumors, especially high heme oxygenase (HO‐1) and glutathione (GSH) levels. Herein, PEGylated CuMoO x ‐coated and zinc protoporphyrin IX (ZP)‐loaded Cu (CCMZ) NPs are designed to afford rapid degradation ability and augmented CDT efficacy through inhibiting HO‐1 activity and depleting GSH. The deep penetration of tumor can be achieved under the high levels of GSH, which triggers the degradation of CuMoO x shell. Meanwhile, GSH itself is depleted, which converts the reductive environment into constant oxidative environment, thus leading to the degradation of Cu core. Furthermore, the release of ZP from CCMZ NPs can inhibit HO‐1 activity and provide a favorable microenvironment for CDT, and the release of Cu and Mo ions can convert hydrogen peroxide into hydroxyl radical to eliminate tumor cells more efficiently. In addition, CCMZ NPs also play an immune vaccine‐like effect to recruit different immune cells for antitumor immunotherapy. In vitro and in vivo studies prove the augmented CDT property of CCMZ NPs, supplying a new strategy for improving CDT efficacy.