Estrellas sobre fondos cambiantes: convocando la luz

[EN] Following a seven year period dedicated to the creation and development of nineteen manuscript poems, which today are considered a synthesis of his thinking, in 1955 Le Corbusier published his Poème de l´Angle Droit. The study of this poem reveals the principal themes that dominated his trajectory, as well as a series of elements, namely the sword, the cloud and the star, which appear in his pictorial and architectural work. This paper aims to shed light on the connections established between one of these elements in particular —the star— and its incorporation into Lecorbuserian method of architectural design. It seeks to analyse how this item is repeated obsessively, forming images which remain rooted in the architectural strategies developed by the Swiss architect. The star speaks of a lighthouse, a guide, a driving force that spurs on the journey. It is the element that represents the mobility of the cosmos, which governs the nature of repetition linked to art; a signal that guides the traveler and traces the route their steps must take them, leading us to think of a bright light and the distance that separates the real and the imagined. And above all, it is the reference in those buildings that condensed the reflections that gave coherence and unity to the various project options.[ES] Tras crear y desarrollar durante siete años diecinueve poemas manuscritos, que hoy en día son considerados síntesis de su pensamiento, Le Corbusier publicó en 1955 su Poème de l´Angle Droit. Al estudiar este poema reconocemos en él los principales temas presentes en su trayectoria, así como algunos elementos —la espada, la nube y la estrella— que aparecen en su obra pictórica y arquitectónica. La presente comunicación pretende desvelar las conexiones que se establecen entre uno de estos elementos en concreto, como es la imagen de la estrella, y su incorporación al proceso de proyecto lecorbusieriano. Se trata de analizar cómo este tema, que se repite de forma obsesiva, configura imágenes que permanecen en las estrategias arquitectónicas que llevó a cabo el maestro suizo. La estrella habla de faro, de guía, de motor dentro de un proceso de viaje. Es el elemento que representa la movilidad del cosmos, que rige ese carácter de repetición ligado al arte; una señal que guía al viajero y define el itinerario que deben seguir sus pasos, que nos hace pensar en una brillante luz y en la distancia entre lo real y lo imaginado. Y, sobre todo, es la referencia presente en edificios, que condensaban así reflexiones que daban coherencia y unidad a las distintas opciones del proyecto.Álvarez Gallego, I.; Blanco Agüeira, S. (2016). Estrellas sobre fondos cambiantes: convocando la luz. En LE CORBUSIER. 50 AÑOS DESPUÉS. Editorial Universitat Politècnica de València. 99-113. https://doi.org/10.4995/LC2015.2015.980OCS9911

The role of an electronic alert system to detect acute kidney injury in hospitalized patients: DETECT-H Project

Background and aims: Acute kidney injury (AKI) is associated with higher mortality and length of stay (LOS) for hospitalized patients. To improve outcomes, an electronic detection system could be a useful tool for early diagnosis. Methods: A fully automated real-time system for detecting decreased glomerular filtration rate in adult patients was developed in our hospital, DETECT-H project. AKI was established according to KDIGO guidelines. Results: In six months, 1241 alerts from 11,022 admissions were issued. Overall incidence of AKI was 7.7%. Highest AKI stage reached was: stage 1 (49.8%), 2 (24.5%) and 3 (25.8%), in-hospital mortality was 10.9%, 22.7%, 33.9% respectively and 57.1% in AKI requiring dialysis; mortality in stable CKD was 4.3%. Median LOS was 8 days versus 5 days for all patients. AKI was associated with a mortality of 3.18 (95% CI 1.80–5.59) and a LOS 1.52 (1.11–2.08) times as high as that for admissions without AKI. Multivariate analysis indicated that a LOS higher than 8 days was associated with AKI. Previous CKD was noted in 31.9% and AKI in 45.3% at discharge. As compared to the use of the detect system, only one third of CKD patients and half of AKI episodes were identified. Conclusions: CKD and in-hospital AKI are under-recognized entities. Mortality and LOS are increased in-hospital patients with renal dysfunction. AKI severity was associated with higher mortality and LOS. An automated electronic detection system for identifying renal dysfunction would be a useful tool to improve renal outcomes. Resumen: Introducción y objetivos: El fracaso renal agudo (FRA) aumenta la mortalidad y la estancia hospitalarias (EH). El empleo de sistemas de detección electrónica podría ser una herramienta beneficiosa para mejorar estos resultados. Métodos: Se desarrolló un sistema de detección automático a tiempo real de pacientes ingresados con función renal alterada, denominado proyecto DETECT-H. El FRA se estableció de acuerdo con las guías KDIGO. Resultados: En 6 meses, 1.241 alertas fueron recogidas de 11.022 ingresos. La incidencia global del FRA fue del 7,7%. La distribución en función del estadio máximo del FRA alcanzado fue: estadio 1: 49,8%, estadio 2: 24,5% y estadio 3: 25,8%; con una mortalidad hospitalaria del 10,9, 22,7 y 33,9%, respectivamente. En el caso del FRA con necesidad de diálisis fue del 57,1%. La mortalidad en pacientes con enfermedad renal crónica (ERC) estable fue del 4,3%. La mediana de EH en pacientes detectados fue 8 vs. 5 días para todos los pacientes hospitalizados. El FRA se asoció con una mortalidad 3,18 (1,8-5,59) y una EH 1,52 (1,11-2,08) veces superior que aquellos ingresos sin FRA. El análisis multivariante indicó que el FRA se asociaba con la EH > 8 días.En los informes de alta, la presencia de ERC previa solo fue registrada en el 31,9% de los pacientes con ERC y el FRA hospitalario en el 45,3%. Conclusiones: La ERC y el FRA intrahospitalario son entidades infradiagnosticadas. La mortalidad y la EH están aumentadas en pacientes con disfunción renal. La gravedad del FRA se asoció con mayor mortalidad y EH. Un sistema de detección automático para identificarlos podría ser útil para mejorar estos resultados. Keywords: Acute kidney injury, Automated electronic detection system, Chronic kidney disease, Diagnosis, Health information technology, Mortality, Palabras clave: Fracaso renal agudo, Sistema de detección electrónica automática, Enfermedad renal crónica, Diagnóstico, Tecnología de información de la salud, Mortalida

Caveolin-1 is down-regulated in alveolar habdomyosarcomas and negatively regulates tumor growth

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of less than 30%. Caveolin-1 (CAV1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling. In the present study we report that compared to other forms of rhabdomyosarcoma (RMS) CAV1 expression is either undetectable or very low in ARMS cell lines and tumor samples. DNA methylation analysis of the promoter region and azacytidine-induced re-expression suggest the involvement of epigenetic mechanisms in the silencing of CAV1. Reintroduction of CAV1 in three of these cell lines impairs their clonogenic capacity and promotes features of muscular differentiation. In vitro, CAV1-expressing cells show high expression of Caveolin-3 (CAV3), a muscular differentiation marker. Blockade of MAPK signaling is also observed. In vivo, CAV1-expressing xenografts show growth delay, features of muscular differentiation and increased cell death. In summary, our results suggest that CAV1 could function as a potent tumor suppressor in ARMS tumors. Inhibition of CAV1 function therefore, could contribute to aberrant cell proliferation, leading to ARMS development

Incremento de peso en pacientes con fibrosis quística: ¿es siempre beneficioso?

Introduction: The primary objective of this study was to find out the prevalence of overweight and obese status, as well as their association to pulmonary function, total cholesterol and vitamin D in patients with cystic fibrosis (CF). Materials and methods: This is a multicenter descriptive and cross-sectional study. Twelve Spanish hospitals participated. 451 patients with CF were included. Adults were classified according to body mass index (BMI) and children were classified according to BMI percentiles (WHO tables). Pearson’s correlation, Anova, Student’s t-test and multiple linear regression were conducted. Results: Mean age was 12.3 (range 4-57) years old, 51% were male and 18% had pancreatic sufficiency. Participants were classified in five nutritional status categories: 12% were malnourished; 57%, at nutritional risk; 24%, normally nourished; 6%, overweight; and 1%, obese. Pulmonary function in overweight or obese patients (91 ± 19%) was better than in malnourished patients (77 ± 24%) (p = 0.017). However, no difference was observed between those at nutritional risk (86 ± 19%) or normally nourished (90 ± 22%) groups. Overweight and obese patients had higher levels of total cholesterol (p = 0.0049), a greater proportion of hypercholesterolemia (p = 0.001), as well as lower levels of 25 OH vitamin D (p = 0.058). Conclusions: Prevalence of overweight and obese was 6 and 1%. Excess weight status does not offer any benefit in pulmonary function in comparison to normally nourished patientsIntroducción y objetivos: conocer la prevalencia de sobrepeso y obesidad, así como su asociación con la función pulmonar, el colesterol total y la vitamina D en pacientes con fi brosis quística (FQ). Material y métodos: estudio multicéntrico descriptivo y transversal. Participaron 12 hospitales españoles. Fueron incluidos 451 pacientes con FQ, clasifi cados según el índice de masa corporal (IMC) en adultos y el IMC percentilado (tablas OMS) en niños. Análisis estadístico: C.Pearson, Anova, t de Student y regresión lineal múltiple. Resultados: la mediana de edad fue 12,3 (rango 4-57) años. Un 51% eran varones y el 18%, sufi cientes pancreáticos (SP). El 12% estaba desnutrido; el 57%, en riesgo nutricional; el 24%, normonutrido; el 6% presentaba sobrepeso; y un 1%, obesidad. La función pulmonar en los pacientes con sobrepeso (91 ± 19%) era mejor que en los desnutridos (77 ± 24%) (p = 0,017), sin embargo, no se observaron diferencias con respecto a los que estaban en riesgo nutricional (86 ± 19%) o normonutridos (90 ± 22%). Los pacientes con sobrepeso tenían más elevado el colesterol total (p = 0,0049), mayor proporción de hipercolesterolemia (p = 0,001), así como niveles más bajos de 25 OH vitamina D (p = 0,058). Conclusiones: la prevalencia de sobrepeso y obesidad fue del 6 y el 1%. El sobrepeso y la obesidad no ofrecen benefi cio sobre la función pulmonar en comparación con los normonutrido

The natural history of QTc interval and its clinical impact in coronavirus disease 2019 survivors after 1 year

Background and objectiveProlonged QTc interval on admission and a higher risk of death in SARS-CoV-2 patients have been reported. The long-term clinical impact of prolonged QTc interval is unknown. This study examined the relationship in COVID-19 survivors of a prolonged QTc on admission with long-term adverse events, changes in QTc duration and its impact on 1-year prognosis, and factors associated with a prolonged QTc at follow-up.MethodsWe conducted a single-center prospective cohort study of 523 SARS-CoV-2-positive patients who were alive on discharge. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval and repeated in 421 patients 7 months after discharge. Mortality, hospital readmission, and new arrhythmia rates 1 year after discharge were reviewed.ResultsThirty-one (6.3%) survivors had a baseline prolonged QTc. They were older, had more cardiovascular risk factors, cardiac disease, and comorbidities, and higher levels of terminal pro-brain natriuretic peptide. There was no relationship between prolonged QTc on admission and the 1-year endpoint (9.8% vs. 5.5%, p = 0.212). In 84% of survivors with prolonged baseline QTc, it normalized at 7.9 ± 2.2 months. Of the survivors, 2.4% had prolonged QTc at follow-up, and this was independently associated with obesity, ischemic cardiomyopathy, chronic obstructive pulmonary disease, and cancer. Prolonged baseline QTc was not independently associated with the composite adverse event at 1 year.ConclusionsProlonged QTc in the acute phase normalized in most COVID-19 survivors and had no clinical long-term impact. Prolonged QTc at follow-up was related to the presence of obesity and previously acquired chronic diseases and was not related to 1-year prognosis

doi.org/10.1371/journal. pone.0250796

The aim was to analyze the characteristics and predictors of unfavorable outcomes in solid organ transplant recipients (SOTRs) with COVID-19. We conducted a prospective observational cohort study of 210 consecutive SOTRs hospitalized with COVID-19 in 12 Spanish centers from 21 February to 6 May 2020. Data pertaining to demographics, chronic underlying diseases, transplantation features, clinical, therapeutics, and complications were collected. The primary endpoint was a composite of intensive care unit (ICU) admission and/or death. Logistic regression analyses were performed to identify the factors associated with these unfavorable outcomes. Males accounted for 148 (70.5%) patients, the median age was 63 years, and 189 (90.0%) patients had pneumonia. Common symptoms were fever, cough, gastrointestinal disturbances, and dyspnea. The most used antiviral or host-targeted therapies included hydroxychloroquine 193/200 (96.5%), lopinavir/ritonavir 91/200 (45.5%), and tocilizumab 49/200 (24.5%). Thirty-seven (17.6%) patients required ICU admission, 12 (5.7%) suffered graft dysfunction, and 45 (21.4%) died. A shorter interval between transplantation and COVID-19 diagnosis had a negative impact on clinical prognosis. Four baseline features were identified as independent predictors of intensive care need or death: advanced age, high respiratory rate, lymphopenia, and elevated level of lactate dehydrogenase. In summary, this study presents comprehensive information on characteristics and complications of COVID-19 in hospitalized SOTRs and provides indicators available upon hospital admission for the identification of SOTRs at risk of critical disease or death, underlining the need for stringent preventative measures in the early post-transplant periodThis study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016); co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligence Growth 2014-2020. EC and JSC received grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARSCoV-2 y la enfermedad COVID-19 (COV20/ 00370; COV20/00580). JSC is a researcher belonging to the program “Nicola´s Monardes”(C0059–2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain. SS-A is supported by a grant from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-Co

Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives

BACKGROUND Disease penetrance in genotype -positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS The authors evaluated 779 G+ patients (age 35.8 +/- 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN ) without DCM followed at 25 Spanish centers. RESULTS After a median follow-up of 37.1 months (Q1 -Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person -years; 95% CI: 2.3-3.5 per 100 person -years). DCM penetrance and age at DCM onset was different according to underlying gene group (log -rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1 -year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end -diastolic diameter (HR per 1 -mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identi fied late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end -diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM. (J Am Coll Cardiol 2024;83:1640 -1651) (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Vitamin d and chronic lung colonization in pediatric and young adults cystic fibrosis patients

Introducción y objetivos: conocer la situación en la que se encuentran los pacientes con fibrosis quística en relación con sus niveles de vitamina D y su asociación con las colonizaciones pulmonares crónicas. Material y métodos: estudio multicéntrico transversal. Participaron 12 hospitales nacionales. De noviembre a abril del 2012 al 2014 se incluyeron 377 pacientes con fibrosis quística. Se consideraron insuficientes niveles de vitamina D < 30 ng/ml. Presentar al menos dos cultivos positivos en el último año fue considerado un criterio de colonización crónica. Resultados: los pacientes tenían una mediana de edad de 8,9 años (2 meses—20 años). Un 65% presentaban niveles insuficientes de vitamina D. Se observó una correlación inversa entre edad y niveles de vitamina D (r = -0,20 p < 0,001). Los diagnosticados por cribado eran más jóvenes y tenían niveles de vitamina D más altos. Los niveles de vitamina D presentaron una correlación inversa con el número de colonizaciones pulmonares (r = -0,16 p = 0,0015). Ajustando por edad, función pancreática y diagnóstico mediante cribado, la colonización por S. Aureus en menores de seis años y por Pseudomonas sp. en los mayores de esa edad, incrementaban el riesgo de presentar niveles insuficientes de vitamina D: OR 3,17 (IC95% 1,32-7,61) (p=0,010) y OR 3,77 (IC95% 1,37- 10,37)(p = 0,010), respectivamente. Conclusiones: a pesar de una suplementación adecuada, más de la mitad de nuestros pacientes no alcanzan niveles óptimos de vitamina D. La colonización crónica por Pseudomonas sp. en escolares y adolescentes y por S. Aureus en lactantes y preescolares se asocia de forma independiente con la deficiencia de vitamina D.Introduction and objectives: evaluate vitamin D status and its association with chronic lung colonisation in Cystic Fibrosis patients. Material and methods: descriptive cross-sectional multicenter study. From November 2012 to April 2014, at 12 national hospitals, 377 patients with Cystic Fibrosis were included. Vitamin D levels < 30 ng/ml were classified as insufficient. Chronic colonisation was considered if they had at least two positive cultures in the past year. Results: the median age was 8.9 years (2 months to 20 years). 65% had insufficient levels of vitamin D. There was an inverse correlation between age and vitamin D levels (r = -0.20 p < 0.001). Those diagnosed by screening, were younger and had higher levels of vitamin D. There was an inverse correlation between the number of colonisations and vitamin D levels (r = -0.16 p = 0.0015). Adjusting for age, pancreatic status and diagnosis by screening, colonization by S. aureus in <6 years and Pseudomonas sp. in > 6 years, increased the risk of insufficient levels of vitamin D: OR 3.17 (95% CI 1.32 to 7.61) (p = 0.010) and OR 3.77 (95% CI 1.37 to 10 , 37) (p = 0.010), respectively. Conclusions: despite adequate supplementation, more than half of our patients did not achieve optimal levels of vitamin D. Regardless of age, diagnosis by screening or pancreatic status, chronic colonization by Pseudomonas sp. in children and adolescents and S. Aureus in infants and preschoolars increases the risk of developing vitamin D deficiency in these patients.S

Single nucleotide variations in ZBTB46 are associated with post-thrombolytic parenchymal haematoma

Haemorrhagic transformation is a complication of recombinant tissue-plasminogen activator treatment. The most severe form, parenchymal haematoma, can result in neurological deterioration, disability, and death. Our objective was to identify single nucleotide variations associated with a risk of parenchymal haematoma following thrombolytic therapy in patients with acute ischaemic stroke. A fixed-effect genome-wide meta-analysis was performed combining two-stage genome-wide association studies (n = 1904). The discovery stage (three cohorts) comprised 1324 ischaemic stroke individuals, 5.4% of whom had a parenchymal haematoma. Genetic variants yielding a P-value < 0.05 1 x 10(-5) were analysed in the validation stage (six cohorts), formed by 580 ischaemic stroke patients with 12.1% haemorrhagic events. All participants received recombinant tissue-plasminogen activator; cases were parenchymal haematoma type 1 or 2 as defined by the European Cooperative Acute Stroke Study (ECASS) criteria. Genome-wide significant findings (P < 5 x 10(-8)) were characterized by in silica functional annotation, gene expression, and DNA regulatory elements. We analysed 7 989 272 single nucleotide polymorphisms and identified a genome-wide association locus on chromosome 20 in the discovery cohort; functional annotation indicated that the ZBTB46 gene was driving the association for chromosome 20. The top single nucleotide polymorphism was rs76484331 in the ZBTB46 gene [P = 2.49 x 10(-8); odds ratio (OR): 11.21; 95% confidence interval (CI): 4.82-26.55]. In the replication cohort (n = 580), the rs76484331 polymorphism was associated with parenchymal haematoma (P = 0.01), and the overall association after meta-analysis increased (P = 1.61 x 10(-8), OR: 5.84; 95% CI: 3.16-10.76). ZBTB46 codes the zinc finger and BTB domain-containing protein 46 that acts as a transcription factor. In silica studies indicated that ZBTB46 is expressed in brain tissue by neurons and endothelial cells. Moreover, rs76484331 interacts with the promoter sites located at 20q13. In conclusion, we identified single nucleotide variants in the ZBTB46 gene associated with a higher risk of parenchymal haematoma following recombinant tissue-plasminogen activator treatment.Peer reviewe

Antimicrobial Defined Daily Dose in Neonatal Population: Validation in the Clinical Practice

Paediatric Antimicrobial Defined Daily Dose Study Group KiDDDs.Currently, there is no validated method for estimating antimicrobial consumption in the neonatal population, as it exists for adults using Defined Daily Doses (DDD). In neonatology, although there are different methods, each one with advantages and disadvantages, there is no unified criterion for use. The aim of this study is to validate the neonatal DDD designed as a new standardised form of antimicrobial consumption over this population.M.M.-T. received financial support from the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain (CM21/00115). The project has been carried out without financial funding but is supported by the Spanish Society of Hospital Pharmacy (SEFH), the Working Group on Pharmaceutical Care in Infectious Diseases of the SEFH (Afinf) and Spanish working group on paediatric pharmacy of the SEFH (gefp).Peer reviewe