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Background:Perseverance in pharmacological treatment for osteoporosis is a key factor in fracture prevention. Denosumab has demonstrated superior persistence compared to other anti-osteoporotic drugs in previous studies. Patient-related factors may influence treatment persistence.Objectives:To describe the characteristics of a cohort of patients undergoing denosumab treatment. To assess clinical and/or demographic characteristics that are significantly associated with treatment persistence.Methods:Patients diagnosed with osteoporosis aged over 50, visited in Rheumatology outpatient clinics of three hospitals in Tarragona, who were prescribed denosumab between January 2013 and December 2023 and had received at least two doses of denosumab. Clinical and demographic data were collected from the patients’ medical records. Logistical regression analysis was conducted to examine the relationship between different factors and treatment persistence. The variables studied included age, gender, polypharmacy, Charlson index, cognitive status, fracture risk, use of psychoactive drugs, previous osteoporotic fractures and previous osteoporosis treatments.Results:A total of 854 patients were recruited. Patients lost to treatment due to death (130 patients) and withdrawal due to improvement according to medical criteria (108) were excluded. 616 patients were analyzed. The characteristics of these patients are shown in Table 1. A total of 468 patients continued with treatment (76%) while 148 discontinued it (24%). The mean follow-up time was 59 months (minimum 12 – maximum 144). Variables significantly associated with lower treatment discontinuation were previous osteoporosis treatment (OR=0.67; CI: 0.48-0.93); polypharmacy with 5-10 drugs (OR 0.66; CI 0.45-0.95); polypharmacy with more than 10 drugs (OR 0.6; CI 0.37-0.97). The variable significantly associated with higher discontinuation was dementia (OR 1.96; CI 1.34-2.89).Conclusion:The studied cohort comprises an aging population with high comorbidity, a significant presence of dementia, and polypharmacy. Denosumab treatment persistence is significantly influenced by patient’s cognitive status, use of more than 5 drugs, and having received previous osteoporosis treatments. These factors should be considered when initiating long-term treatments, reevaluating the type of treatment, and reinforcing follow-up for these patients.Table 1.Characteristics of the analyzed populationN = 616Age (median, IQR)81 (74 – 87)Sex (n women, %)560, 90.90%Cognitive state (n, %) Good470, 76.30% Mild dementia115, 18.66% Moderate dementia30, 4.87%Densitometry at diagnosis (yes, %)416, 67.53%Column densitometry values T-score (median, IQR)-3.10 (-3.70 - -2.37)Hip densitometry values T-score (median, IQR)-2.50 (-2.90 - -1.90)Vitamin D values before starting treatment ng/dl (median, IQR)33.80 (28 – 44)Osteoporosis risk (n, %) High263, 42.69% Very high353, 57.31%Charlson index (median, IQR)4 (3 – 6)Psychoactive drugs (yes, %)311, 50.49%Corticoids (n, %) Up to 5 mg prednisone63, 10.22% More than 5 mg prednisone27, 4.38% No524, 85.06%Polypharmacy (n, %) Up to 5 different drugs205, 33.28% Between 5 and 10293, 47.56% More than 10116, 18.83%Previous osteoporotic fracture (n, %) Other fractures23, 3.73% Hip122, 19.81% Vertebral204, 33.11% No186, 30.19%Previous osteoporosis treatment (n, %) IV Bisphosphonates25, 4.06% Oral bisphosphonates213, 34.58% Teriparatide102, 16.56% No274, 44.48%REFERENCES:[1]   Reyes C, et al. One and two-year persistence with different anti-osteoporosis medications: a retrospective cohort study. Osteoporos Int. 2017 Oct;28(10):2997-3004.[2]   Llop C, et al. Cumplimiento y permanencia de los tratamientos para la osteoporosis en pacientes con fractura de cadera. Aten primaria 2020;52(9):659-660.Acknowledgements:NIL.Disclosure of Interests:Silvia Paredes Galapagos, Novartis, Lilly, Amgen, Abbvie, Delia Taverner Janssen, Galapagos, Abbvie, Novartis, Ester Costa Janssen, Galapagos, Anna Pàmies Lilly, Galapagos, Amgen y Novartis, Carles Tomas: None declared, Didac Llop: None declared, Carles Llop: None declared.

BackgroundRheumatoid arthritis (RA) causes problems beyond the joints such as cardiovascular (CV) disease. It is estimated that the risk of developing CV disease in RA patients is approximately 50% higher than that in the general population[1]. The formation of atherosclerotic plaques is the main mechanism of the development of CV disease in RA patients[2]. The pathogenesis of atherosclerotic plaques is multifactorial and includes vascular, metabolic and inflammatory components[3]. In this regard, miRNA-24, 146 and Let7a have previously been associated with the presence of carotid plaques in RA patients[4].ObjectivesGiven that there is a strong relationship between the chronic inflammatory state of RA and arteriosclerosis, we evaluated, individually and globally, whether miRNA-24, 146 and Let7a were involved in the inflammatory state of RA and could link inflammation and arteriosclerosis.MethodsA total of 199 patients with RA were included. Inflammatory variables such as disease activity score 28 (DAS28) and erythrocyte sedimentation rate (ESR) were quantified. MicroRNAs were extracted from plasma and quantified with qPCR. Multivariate models were used for analysis. An expression score was created to evaluate all the miRNAs conjunctively.ResultsThe multivariate models showed that miRNA-146 was significantly associated with DAS28 (β = -0.15), and miRNAs 24, 146 and Let7a were significantly associated with ESR (β = -5.17, β = -5.29 and β = -6.47, respectively) in the overall cohort. When miRNAs were evaluated globally, they were also significantly associated with DAS28 and ESR in the overall cohort (β = 0.41 and β = 14.23, respectively). Sex-stratified analyses also showed different associations of these miRNAs with the inflammatory variables (Table 1).ConclusionPlasmatic expressions of miRNA-24, 146 and Let7a were associated with inflammatory markers of RA. These miRNAs are associated with both inflammation and atherosclerosis, which could link these processes, and are potential therapeutic targets for RA.References[1]Castañeda S, Martín-Martínez MA, González-Juanatey C, Llorca J, García-Yébenes MJ, Pérez-Vicente S, et al. Cardiovascular morbidity and associated risk factors in Spanish patients with chronic inflammatory rheumatic diseases attending rheumatology clinics: Baseline data of the CARMA Project. Semin Arthritis Rheum. 2015;44:618–26.[2]Ambrosino P, Lupoli R, Di Minno A, Tasso M, Peluso R, Di Minno MND. Subclinical atherosclerosis in patients with rheumatoid arthritis. A meta-analysis of literature studies. Thromb Haemost. 2015;113:916–30.[3]Wolf D, Ley K. Immunity and Inflammation in Atherosclerosis. Circ Res. 2019;124:315–27.[4]Llop D, Ibarretxe D, Plana N, Rosales R, Taverner D, Masana L, et al. A panel of plasma microRNAs improves the assessment of surrogate markers of cardiovascular disease in rheumatoid arthritis patients. Rheumatology (Oxford). 2022.Table 1.Summaries of the multivariate lineal regression models to estimate the associations between miRNAs and DAS28 and ESR in the overall cohort and stratified by sex. Basal models are adjusted for age, sex, body mass index, disease onset, disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, corticosteroids and biological drugs. β = beta coefficient, p = p-value.MiRNAs association with DAS28 and ESRβpR2 (%)DAS28OVERALL COHORTBasal Model12.75+ miRNA – 146-0.150.0414.16+ Expression Score0.410.04915.30MENBasal Model13.91+ miRNA – 146-0.230.0222.06+ Expression Score0.780.0126.34ESROVERALL COHORTBasal Model10.57+ miRNA – 24-5.170.00215.25+ miRNA – 146-5.290.000316.41+ miRNA – Let7a-6.470.000516.15+ Expression Score14.23<0.000118.63MENBasal Model15.73+ miRNA – 24-5.180.0323.16+ miRNA – 146-5.010.0124.84+ miRNA – Let7a-6.540.0224.03+ Expression Score14.790.0126.37WOMENBasal Model9.95+ miRNA – 24-5.290.0213.97+ miRNA – 146-5.550.00814.82+ miRNA – Let7a-6.370.0114.48+ Expression Score15.260.00817.29AcknowledgementsWe would like to thank all the patients for their essential collaboration.Disclosure of InterestsSILVIA PAREDES Speakers bureau: Lilly, Bristol, Amgen, Consultant of: Galapagos, Sanofi, Bristol, Didac Llop: None declared, Daiana Ibarretxe Speakers bureau: Sanofi, Sobi, Genzyme, Rubio, Delia Taverner Speakers bureau: Galapagos, Amgen, Roser Rosales: None declared, Nuria Plana Speakers bureau: Amgen, Sanofi, Servier, Consultant of: Servier, Luis Masana Speakers bureau: Amgen, Sanofi, Servier, Consultant of: Servier, Amgen, Joan Carles Vallve: None declared.

BackgroundPatients with rheumatoid arthritis (RA) present increased risk of cardiovascular (CV) disease compared to the general population. Moreover, CV risk factors that have causal relationship with atherosclerosis do not seem to fully explain the accelerated process that they exhibit[1]. Over the years, several serum growth factors have been associated with atherosclerosis and some of them have been targeted as potential immunotherapy targets for the treatment of CV disease[2,3]. However, very few studies have studied these associations in RA patients.ObjectivesWe evaluated the association of 8 plasmatic growth factors (angiopoietin-2, EGF, HB-EGF, PLGF, TGF-α, VEGFa, VEGFc, VEGFd) with surrogate markers of subclinical arteriosclerosis (carotid intima media thickness (cIMT), carotid plaque presence (cPP) and pulse wave velocity (PWV)) in a cohort of RA patients.MethodsA total of 199 patients with RA were included. Subclinical markers of arteriosclerosis, (cIMT, cPP and PWV) were measured with the My Lab 50 X-Vision sonogram. The different plasmatic growth factors were measured with Bio-Plex Pro Human Cancer Biomarker Panel 2, from BIO-RAD. Multivariate models and Partial Least Square Discriminant Analysis (PLS-DA) were used for analysis. Analyses were performed in the overall cohort and stratified by sex.ResultsThe multivariate models showed that angiopoietin-2 was significantly associated with cPP and PWV in the overall cohort. Moreover, VEGFc was also associated with PWV. Stratified analyses showed that VEGFa, VEGFd, EGF, PLGF, HB-EGF were associated with cPP in men patients. In this direction, PLS-DA analysis showed that the mentioned growth factors properly classified patients with and without cPP (Figure 1). Furthermore, angiopoietin-2, EGF, VEGFc, VEGFa, HB-EGF were associated with PWV. Regarding women, angiopoietin-2 was associated with PWV. Result from the lineal and logistic regressions are summarized in Table 1.ConclusionPlasmatic growth factors, especially in men, are highly associated with subclinical arteriosclerosis surrogate markers and could be potential predictors of CV disease in patients with RA.References[1]Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies. Arthritis Care Res. 2008;59:1690–7.[2]Mindur JE, Swirski FK. Growth Factors as Immunotherapeutic Targets in Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2019;39:1275–87.[3]Domouzoglou EM, Naka KK, Vlahos AP, Papafaklis MI, Michalis LK, Tsatsoulis A, et al. Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21. Am J Physiol - Hear Circ Physiol. 2015;309:H1029.Table 1.Summaries of the multivariate lineal and logistic regression models to estimate the associations between growth factors (GF) and cPP and PWV in the overall cohort and stratified by sex. Basal models are adjusted for age, sex, body mass index, disease onset, disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, corticosteroids, biological drugs and DAS28. GF = growth factor, β = beta coefficient, OR = odds ratio, p = p-valueGF associations with subclinical arteriosclerosisORpR2 (%)cPPOVERALL COHORTBasal Model24+ angiopoietin-21.00050.0226MENBasal Model33+ VEGFa1.0020.0439+ VEGFd1.0020.0438+ EGF1.020.0240+ PLGF1.010.0339+ HB-EGF1.020.0438BpR2 (%)PWVOVERALL COHORTBasal Model32+ angiopoietin-20.00060.00136+ VEGFc0.00050.0434MENBasal Model33+ angiopoietin-20.00070.0240+ VEGFa0.0020.0239+ VEGFc0.0010.00841+ HB-EGF0.010.0438WOMENBasal Model36+ angiopoietin-20.00050.0139Figure 1.PLS-DA of men with cPP and without cPP, adjusted for the significant growth factors and age, body mass index, disease onset, disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, corticosteroids, biological drugs and DAS. 28 0 = no cPP, 1 = cPPAcknowledgementsWe would like to thank all patients for their essential collaboration.Disclosure of InterestsANNA PAMIES CORTS Speakers bureau: Novartis, Galapagos, Didac Llop: None declared, Daiana Ibarretxe Speakers bureau: Sanofi, Sobi, Genzyme, Rubio, Delia Taverner Speakers bureau: Galapagos, Amgen, Roser Rosales: None declared, Nuria Plana Speakers bureau: Amgen, Sanofi, Servier, Consultant of: Servier, Luis Masana Speakers bureau: Amgen, Sanofi, Servier, Consultant of: Servier, Amgen, Joan Carles Vallve: None declared, Silvia Paredes Speakers bureau: Lilly, Bristol, Amgen, Consultant of: Galapagos, Sanofi, Bristol.

Background/Objectives: To compare body fat mass at the same stage of pubertal maturation, genital stage 2 (G2), in a Spanish and in a Mexican sample of boys. Subjects/Methods: Data from Spain ( n =177) were from a previous longitudinal clinical follow-up and data from Mexico ( n =91) from a cross-sectional study. Subjects were grouped according to the presence of G2 at similar ages. Spanish sample was divided into boys with G2 at age 12 ( n =60), 13 ( n =74) and 14 ( n =43). In Mexican sample, 23 boys were at G2 at 12 years, 38 at age 13 and 30 at 14 years. Height, weight, upper arm circumference and four skinfold thicknesses were recorded. Genital development was assessed (Tanner scale). Sum of four skinfolds (SUM), body mass index (BMI), percentage of body fat (%BF) and extremity/trunk skinfold ratio (ETR=(triceps+biceps)/(subscapular+suprailiac)) was calculated. Results: When comparing subjects with different ages at G2 from the same country, or with the same age at G2 from different countries, no significant differences were found in adiposity variables (%BF, SUM), nor in BMI. Nevertheless, there were differences in body fat distribution: ETR was higher in Spanish boys ( P <0.001), because of their greater triceps skinfold thickness ( P =0.013), and due to the greater trunk fat stores in Mexican boys ( P <0.01, subscapular and suprailiac skinfolds). Conclusions: There is a subcutaneous fat mass store characteristic of G2 in boys, which is not only independent of age, but is also observable in two different populations.

To describe the genetic diversity of enteroviruses (EV) causing hand, foot and mouth disease (HFMD) and herpangina, especially of coxsackievirus (CV)-A6, from patients attended at pediatric primary care centers during the 2017-2018 season. Phylogenetic analysis of partial VP1 region was performed for genetic characterization. The complete VP1 and 3Dpol proteins were sequenced for lineage determination and detection of recombination events. An 80% of samples were EV laboratory-confirmed. CV-A6 was the most detected (70%) and associated with atypical HFMD (78%). The comparison of VP1 and 3Dpol phylogenies showed evidence of recombination in three strains, in which two shifted to CV-A16 3Dpol. The study provides recent information regarding the nonrecombinant and recombinant EVs related to HFMD at primary care centers.

Phytosterols present in parenteral nutrition (PN) lipid emulsions have been linked to phytosterolemia and cholestatic liver disease, although no direct relation has been established. We investigated the relation among plasma phytosterol (PY) infused, total plasma PY levels, and possible links to PN-associated liver disease. Twenty-seven adult patients on home PN were enrolled in the study. PYs were measured in plasma and lipid emulsions by gas chromatography. Liver function tests and blood counts were assessed to identify hepatic impairment, and biopsies were performed in eight patients. Mean total plasma PY level was higher in patients than in controls (55.4 ± 6.2 versus 14.8 ± 2.3 μg/mL). Simple linear regression models showed a correlation among total plasma PY, liver function tests, and platelet counts, which was stronger for total bilirubin ( r 2 = 0.53, P = 0.0001) and aspartate aminotransferase ( r 2 = 0.50, P = 0.0001) and weaker for platelet counts ( r 2 = 0.158, P = 0.04); between infused lipid and liver function tests, the correlation was significant for total bilirubin ( r 2 = 0.19, P = 0.038) and aspartate aminotransferase ( r 2 = 0.164, P = 0.049). In multiple linear regression analysis, a decreased oral diet ( b = −52.3, P = 0.001) and infused PY ( b = 2.54, P = 0.093) were risk factors for high plasma PY levels ( r 2 = 0.54). Biopsies showed moderate to severe liver impairment in five patients. Liver damage may be linked to high plasma PY levels and strengthened by lack of an oral diet in patients on home PN.

Of the over 5000 exoplanets that have been detected, only about a dozen have ever been directly imaged. Earth-like exoplanets are on the order of 10 billion times fainter than their host star in visible and near-infrared, requiring a coronagraph instrument to block primary starlight and allow for the imaging of nearby orbiting planets. In the pursuit of direct imaging of exoplanets, scalar vortex coronagraphs (SVCs) are an attractive alternative to vector vortex coronagraphs (VVCs). VVCs have demonstrated 2e-9 raw contrast in broadband light but have several limitations due to their polarization properties. SVCs imprint the same phase ramp as VVCs on the incoming light and do not require polarization splitting, but they are inherently chromatic. Discretized phase ramp patterns such as a wrapped staircase help reduce SVC chromaticity and simulations show it outperforms a chromatic classical vortex in broadband light. We designed, fabricated, and tested a wrapped staircase SVC, and here we present the broadband characterization on the high contrast spectroscopy testbed. We also performed wavefront correction on the in-air coronagraph testbed at NASA's Jet Propulsion Laboratory and achieved an average raw contrasts of 3.2e-8 in monochromatic light and 2.2e-7 across a 10% bandwidth.

The High Contrast spectroscopy testbed for Segmented Telescopes (HCST) is being developed at Caltech. It aims at addressing the technology gap for future exoplanet imagers and providing the U.S. community with an academic facility to test components and techniques for high contrast imaging, focusing on segmented apertures proposed for future ground-based (TMT, ELT) and space-based telescopes (HabEx, LUVOIR). We present an overview of the design of the instrument and a detailed look at the testbed build and initial alignment. We offer insights into stumbling blocks encountered along the path and show that the testbed is now operational and open for business. We aim to use the testbed in the future for testing of high contrast imaging techniques and technologies with amongst with thing, a TMT-like pupil.

1-Aminocyclopropane-1-carboxylic acid synthase (ACS) is one of the key regulatory enzymes involved in the synthesis of the hormone ethylene and is encoded by a multigene family containing at least eight members in tomato (Lycopersicon esculentum). Increased ethylene production accompanies ripening in tomato, and this coincides with a change in the regulation of ethylene synthesis from auto-inhibitory to autostimulatory. The signaling pathways that operate to bring about this transition from so-called system-1 to system-2 ethylene production are unknown, and we have begun to address these by investigating the regulation of ACS expression during ripening. Transcripts corresponding to four ACS genes, LEACS1A, LEACS2, LEACS4, and LEACS6, were detected in tomato fruit, and expression analysis using the ripening inhibitor (rin) mutant in combination with ethylene treatments and the Never-ripe (Nr) mutant has demonstrated that each is regulated in a unique way. A proposed model suggests that system-1 ethylene is regulated by the expression of LEACS1A and LEACS6. In fruit a transition period occurs in which the RIN gene plays a pivotal role leading to increased expression of LEACS1A and induction of LEACS4. System-2 ethylene synthesis is subsequently initiated and maintained by ethylene-dependent induction of LEACS2.