Hospital San Juan de la Cruz

Aortitis associated with giant cell arteritis (GCA) is a severe manifestation, potentially leading to aneurysms and aortic dissection. Tocilizumab (TCZ) has demonstrated efficacy in the treatment of GCA, both intravenously or subcutaneously administered. However, pivotal studies did not specifically evaluate aortic involvement, and no comparison of intravenous (IV) versus subcutaneous (SC) TCZ has been performed in patients with GCA-related aortitis. The objective of this study was to compare the effectiveness of TCZ according to the administration route in patients with GCA-associated aortitis under clinical practice conditions. This was a multicenter observational study including 196 patients diagnosed with GCA-associated aortitis by imaging and treated with TCZ. Patients were grouped by administration route: IV or SC. GCA was diagnosed following the 1990 American College of Rheumatology criteria, temporal artery biopsy, and/or vascular imaging. Aortitis was identified using 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. Main outcomes included EULAR remission, clinical and imaging remission, absence of systemic inflammation, and glucocorticoid-sparing effect. Of 196 patients (148 women; mean age 69.8 ± SD 9.4 years), 110 received IV TCZ and 86 SC TCZ. Baseline clinical characteristics and markers of inflammation were comparable between groups. The glucocorticoid-sparing effect was similar. At 24-month follow-up, EULAR-defined remission was significantly more frequent in the SC group (83.3% vs 80.6%; P < 0.05). However, rates of imaging remission and absence of systemic inflammation were comparable between treatment arms. In this real-world cohort of GCA-associated aortitis, SC TCZ showed slightly greater effectiveness than IV TCZ in achieving EULAR-defined remission, whereas no significant differences were observed between both routes regarding imaging remission.

The interplay of noncovalent interactions is a powerful tool for enhancing charge transport and device morphology in organic electronic systems. Organic semiconductors, characterized by aromatic rings, primarily rely on π-π stacking to form supramolecular structures. However, introducing additional noncovalent interactions, offers alternative routes for tuning aggregation and improving optoelectronic properties. Recently, backbone fluorination has become a powerful molecular design strategy to simultaneously boost charge transport and control the morphology of organic electronic devices. Here we explore the charge transport properties of a series of hydrogen-bonded quinquethiophene-rhodanine semiconductors featuring different fluorinated substituents that are remotely located from the conjugated backbone. By combining optical and vibrational spectroscopy, electrochemistry, microscopy and contactless microwave conductivity techniques, we establish clear correlations between the fluorination degree, supramolecular organization, and charge carrier dynamics. We demonstrate through this molecular design that even though the fluorinated moieties are not incorporated into the conjugated backbone or in the solubilizing alkyl tails, they play an essential role in the final charge transport properties. More importantly, our results provide general design guidelines for fluorinated 2 supramolecular semiconductors, and highlight fluorination in combination with H-bonding as an effective strategy for controlling multiscale structure-property relationships in organic electronic materials.

Background: Swallowed topical corticosteroids (STCs) are used as the first-line therapy for eosinophilic esophagitis (EoE) and have been extensively studied in randomized controlled trials (RCTs); however, the presentation and doses varied widely among the studies. Aim: The goal of this study was to compare the safety and effectiveness of the different STC-based options in EoE patients. Methods: We performed a literature search for RCTs, spanning a time period from database inception to July 2024, in order to compare the efficacy and safety of all STCs used to induce or maintain EoE remission each other and also with placebo or proton pump inhibitors (PPIs) in a network meta-analysis. Outcomes are expressed as pooled risk ratios (RRs) of failure and 95% confidence intervals (CIs), and we aimed to evaluate histological remission at <15–20 eosinophils per high-power field (eos/hpf), <5–6 eos/hpf, and <1 eos/hpf. The effect sizes for symptomatic improvement and the mean differences for endoscopic EREFS improvement with 95% CIs were also measured. Adverse events were evaluated using RRs, and these included oropharyngeal and esophageal candidiasis and adrenal suppression. Results: Twenty studies involving 1455 patients with active EoE reported on STC effectiveness to induce remission; three additional studies on 232 patients assessed the maintenance of remission. Budesonide 1 mg orodispersible tablets ranked highest in SUCRA in terms of all histological remission endpoints. Budesonide from inhalation devices was the only option superior to placebo in improving symptoms. Budesonide viscous suspension was the only option superior to placebo in improving endoscopy. No therapy was significantly associated with the risk of any adverse event. Significant inconsistencies and small study effects were detected in multiple comparisons. Conclusions: Budesonide orodispersible tablets were the best option for achieving EoE histological remission, but not symptomatic or endoscopic improvement. STC formulations were as safe as placebo or PPI.

BackgroundSodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart-failure admission among high-risk patients. However, most patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), have been excluded from randomized trials.MethodsWe conducted this randomized, controlled trial in Spain to evaluate the efficacy of dapagliflozin (at a dose of 10 mg once daily) as compared with standard care alone in patients with aortic stenosis who were undergoing TAVI. All the patients had a history of heart failure plus at least one of the following: renal insufficiency, diabetes, or left ventricular systolic dysfunction. The primary outcome was a composite of death from any cause or worsening of heart failure, defined as hospitalization or an urgent visit, at 1 year of follow-up.ResultsA total of 620 patients were randomly assigned to receive dapagliflozin and 637 to receive standard care alone after TAVI; after exclusions, a total of 1222 patients were included in the primary analysis. A primary-outcome event occurred in 91 patients (15.0%) in the dapagliflozin group and in 124 patients (20.1%) in the standard-care group (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P=0.02). Death from any cause occurred in 47 patients (7.8%) in the dapagliflozin group and in 55 (8.9%) in the standard-care group (hazard ratio, 0.87; 95% CI, 0.59 to 1.28). Worsening of heart failure occurred in 9.4% and 14.4% of the patients, respectively (subhazard ratio, 0.63; 95% CI, 0.45 to 0.88). Genital infection and hypotension were significantly more common in the dapagliflozin group.ConclusionsAmong older adults with aortic stenosis undergoing TAVI who were at high risk for heart-failure events, dapagliflozin resulted in a significantly lower incidence of death from any cause or worsening of heart failure than standard care alone. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT04696185.)

To analyze in a contemporary registry of heart failure (HF) patients followed in specialized HF units in Spain, the differences in clinical features, treatment, and 1-year outcomes in HF with reduced, mildly reduced, and preserved left ventricular ejection fraction. We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Treatment and 1-year mortality, HF hospitalizations and decompensations of HF used were compared according to the type of HF. Of the 1,716 patients, 55.5% had HFrEF, 11.9% had HFmrEF, and 32.6% had HFpEF. HFpEF patients were older and had a higher proportion of women, atrial fibrillation, and hypertension. Sacubitril-valsartan and mineral receptor antagonists were used in greater proportion in HFrEF (56.5% and 73%, respectively, p < 0.001), but also in 10.3 and 33% in HFpEF. One-year mortality (17.3 vs 20.9 vs 15.6/100 persons-year; p = 0.321), 1-year HF hospitalizations (34.4 vs 29.5 vs 26.7/100 persons-year; p = 0.330), and 1-year decompensations of HF without hospitalization (13.1 vs 10.4 vs 11.1; p = 0.393) were similar for the 3 types of HF. In our contemporary cohort of real-life HF patients, slight differences were observed in clinical features and treatment between the 3 types of HF, but the prevalence of most of the major comorbidities and 1-year outcomes (mortality, hospitalizations and decompensations of HF) were similar in the 3 groups.

• Coastal flooding can be assessed through wave run-up in response to various storms. • Coupling remote sensing with numerical approaches improves coastal risk assessment. • Coastal flooding on macrotidal beaches of Normandy is mainly influenced by sea level. • Extreme waves control coastal flooding when changes in water level are limited. • Storms from WSW within the English Channel generate significant coastal flooding. This work examines the impact of coastal storms on a macrotidal beach at Normandy (France), the beach of Villers-sur-Mer, with the aim of assessing coastal flooding. Extreme wave heights and water levels of four typical storms are simulated using the non-hydrostatic model SWASH to estimate the wave run-up. The numerical simulations have been compared to empirical formulations and validated with processed timestacks generated by video monitoring systems (VMS). The validation shows good agreements between observations and simulations with a mean RMSE of 16 cm, which emphasizes the accuracy of this methodological approach. In the light of the overall results, the water level has a predominant effect on the run-up compared to the wave height. However, the combination of high water levels and waves induces the biggest wave run-up, responsible for the most significant flooding on the coast. Additionally, limited changes in water levels during storm events increase the wave height effect on the run-up, meanwhile small waves with short periods cannot uprush the beach. Furthermore, the transfer of storms, integrating the regional scale of the English Channel and the local scale of the beach, is an important step for assessing coastal flooding in semi-open environments and basins, where the wave direction is the conditioning parameter of storm evolution. Storms from WSW within the English Channel generate the highest wave run-up. This research provides an excellent methodological approach and accurate estimations of coastal flooding in Normandy, which is useful for further works on coastal hazards in response to storms.

Introducción: el desarrollo y progresión de la ateroesclerosis y su consecuencia más dramática: el síndrome coronario agudo, implica mecanismos inmunológicos e inflamatorios, por demás en la literatura internacional y nacional se han revelado nuevos marcadores hematológicos de inflamación, que resultan más asequibles y han sido poco explorados en nuestra población.Objetivo: relacionar variables del curso clínico y eventos cardiovasculares mayores adversos ocurridos con marcadores hematológicos de inflamación seleccionados en pacientes hospitalizados por síndrome coronario agudo. Método: Se realizó un estudio descriptivo-transversal de 113 pacientes que ingresaron en la sala de Cardiología con diagnóstico de síndrome coronario agudo durante el 2019. se estableció la relación existente entre variables clínicas, sociodemográficas, electrocardiográficas y ecocardiográficas seleccionadas con marcadores hematológicos y biomoleculares inflamatorios.Resultados: hubo predominio de la enfermedad en adultos mayores, con una mayor proporción de mujeres en edades más avanzadas y mortalidad significativamente mayor. La relación neutrófilos/linfocitos, plaquetas/linfocitos junto al recuento total de leucocitos y la cifra basal de hemoglobina muestran asociación significativamente entre ellos y con la mortalidad, eventos cardiacos mayores adversos y el tipo de síndrome coronario agudoConclusiones: Los marcadores hematológicos de inflamación y estrés oxidativo: relación neutrófilos /linfocitos y plaquetas /linfocitos, tienen una asociación significativa con la mortalidad y eventos cardiacos mayores adversos de pacientes hospitalizados por síndrome coronario agudo y pudieran evaluarse como factores pronósticos teniendo en cuenta su bajo costo y fácil obtención por biometría hemática.

Prematurity is associated with an increased risk of persistent wheezing but the underlying mechanisms are not well defined. The aim of this study was to identify blood transcriptional profiles associated with the development of wheezing in a cohort of moderate to late preterm infants and to define immune gene expression changes associated with wheezing. A convenience sample of a multicenter birth cohort (SAREPREM) of moderate-late preterm children followed during the first 3 years of life was analyzed. Children were enrolled in the first 2 weeks of life (Y0) and longitudinally evaluated at 1 (Y1), 2 (Y2), and 3 years (Y3) of age, for the presence of wheezing and to obtain samples for transcriptional profile analysis. Samples were processed on Illumina HT12 chips and genomic expression analyses performed with R programming, modular analysis for biological function, and QuSAGE for quantitative gene expression. Seventy-six children were included in the study; 33 were classified as non-wheezing and 43 (56.6%) in the wheezing group. At Y0, children who developed wheezing had decreased expression of interferon genes and increased expression of B cell genes compared with the non-wheezing group. These changes in IFN and B cell gene expression were especially significant in children with late/persistent wheezing compared with transient wheezers. Changes in IFN and B lymphocyte gene expression identified in early life suggest the existence of specific immunological mechanisms that play an important role in the development of wheezing in late-preterm infants.

Hispanic/Latino populations are underrepresented in Alzheimer Disease (AD) genetic studies. Puerto Ricans (PR), a three-way admixed (European, African, and Amerindian) population is the second-largest Hispanic group in the continental US. We aimed to conduct a genome-wide association study (GWAS) and comprehensive analyses to identify novel AD susceptibility loci and characterize known AD genetic risk loci in the PR population. Our study included Whole Genome Sequencing (WGS) and phenotype data from 648 PR individuals (345 AD, 303 cognitively unimpaired). We used a generalized linear-mixed model adjusting for sex, age, population substructure, and genetic relationship matrix. To infer local ancestry, we merged the dataset with the HGDP/1000G reference panel. Subsequently, we conducted univariate admixture mapping (AM) analysis. We identified suggestive signals within the SLC38A1 and SCN8A genes on chromosome 12q13. This region overlaps with an area of linkage of AD in previous studies (12q13) in independent data sets further supporting. Univariate African AM analysis identified one suggestive ancestral block (p = 7.2×10-6) located in the same region. The ancestry-aware approach showed that this region has both European and African ancestral backgrounds and both contributing to the risk in this region. We also replicated 11 different known AD loci -including APOE- identified in mostly European studies, which is likely due to the high European background of the PR population. PR GWAS and AM analysis identified a suggestive AD risk locus on chromosome 12, which includes the SLC38A1 and SCN8A genes. Our findings demonstrate the importance of designing GWAS and ancestry-aware approaches and including underrepresented populations in genetic studies of AD.