Cirugía y riesgo de enfermedad de Creutzfeldt-Jakob

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Medicina Preventiva, Salud Pública y Microbiología. Fecha de lectura: 18 de Julio de 2012

Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response

Background: Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW. Methods: Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex. Results: Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2+ /ILC2 percentage was higher in the BCH group than in the RW group (P < .01). TLR3, IL33, IFNG, IL10, and FLG mRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl leukotrienes C4 were evaluated; a significant difference was only found in their ratio. Conclusion: Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells.This study has been partially supported by FIS (Fondo de Investigación Sanitaria—Spanish Health Research Fund) Grants PI15/00803, FI16/00036, PI15CIII/00028, and FEDER Funds (Fondo Europeo de Desarrollo Regional); Alfonso X El Sabio University Grant: VIII Convocatoria Santander‐UAX; and CIBER de Enfermedades Respiratorias (CIBERES), a Carlos III Institute of Health Initiative.S

Differential profile in inflammatory and mineral metabolism biomarkers in patients with ischemic heart disease without classical coronary risk factors

AbstractBackgroundPatients with coronary heart disease (CHD) without classical cardiovascular risk factors (CRFs) are uncommon, and their profile has not been thoroughly studied. In CHD patients, we have assessed the differences in several biomarkers between those with and without CRF.MethodsWe studied 704 patients with CHD, analyzing plasma levels of biomarkers related to inflammation, thrombosis, renal damage, and heart failure: high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), galectin-3, N-terminal fragment of brain natriuretic peptide (NT-pro-BNP), calcidiol (vitamin D metabolite), fibroblast growth factor-23 (FGF-23), parathormone, and phosphate.ResultsTwenty patients (2.8%) exhibited no CRFs. Clinical variables were well balanced in both groups, with the logical exceptions of no use of antidiabetic drugs, lower triglyceride and glucose, and higher high-density lipoprotein cholesterol in no-CRF patients.No-CRF patients showed lower hs-CRP (2.574±3.120 vs. 4.554±9.786mg/L; p=0.018), MCP-1 (114.75±36.29 vs. 143.56±65.37pg/ml; p=0.003), and FGF-23 (79.28±40.22 vs. 105.17±156.61RU/ml; p=0.024), and higher calcidiol (23.66±9.12 vs. 19.49±8.18ng/ml; p=0.025) levels. At follow-up, 10.0% vs. 11.0% patients experienced acute ischemic event, heart failure, or death in the non-CRF and CRF groups, respectively (p=0.815, log-rank test). The limited number of non-CRF patients may have influenced this finding. A Cox regression analysis in the whole population showed that high calcidiol, and low MCP-1 and FGF-23 plasma levels are associated with a better prognosis.ConclusionsCHD patients without CRFs show a favorable biomarker profile in terms of inflammation and mineral metabolism. Further studies are needed to investigate whether this difference translates into a better prognosis

Parathormone levels add prognostic ability to N-terminal pro-brain natriuretic peptide in stable coronary patients

Aims: There are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor-23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well-known biomarkers. Methods and results: In 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hs-TnI), and high-sensitivity C-reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow-up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One-hundred and eighty-five patients developed the primary outcome. FGF23, PTH, hs-TnI, and NT-proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT-proBNP (HR 1.020 [CI 1.012–1.028]; P 85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels. Conclusions: Parathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT-proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.This work was supported by grants from Instituto de Salud Carlos III (ISCIII) and Fondos FEDER (Fondo Europeo de Desarrollo Regional) European Union (PI05/0451, PI14/1567, PI17/01615, and PI17/01495); Spanish Society of Cardiology; Spanish Society of Arteriosclerosis; RECAVA (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares) (RD06/0014/0035); and Instituto de Salud Carlos III FEDER (FJD biobank: RD09/0076/00101). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Revista de educación

Título, resumen y palabras clave en español y en inglésResumen basado en el de la publicaciónSe analiza el efecto de la especialidad cursada en bachillerato sobre el rendimiento académico, tanto en el primer año de universidad como en la titulación en su conjunto, para grados relacionados con Administración y Dirección de Empresas (ADE). A fin de estudiar dicho efecto, se ha llevado a cabo un análisis con datos correspondientes a siete titulaciones diferentes y seis cohortes de alumnos, que accedieron a la universidad entre los cursos 2012-2013 y 2017-2018, obteniéndose una muestra final de 3412 alumnos. Se han ajustado distintos modelos de regresión lineal múltiple adaptados a las peculiaridades de los datos, ya que estos presentaban problemas de heterocedasticidad por los abandonos durante el primer curso, así como multicolinealidad debido a la incorporación de interacciones. Dichos modelos, además de la variable objeto de estudio, incorporan como variables de control aquellas que la literatura previa identifica como predictores clave del rendimiento académico, y se ha utilizado una estrategia de eliminación hacia atrás (Backward Stepwise Selection) para la selección de variables. Los resultados indican que, en grados relacionados con ADE, los alumnos procedentes de un bachillerato de ciencias obtienen, en general, mejores resultados durante el primer año que aquellos que cursaron la especialidad de humanidades y ciencias sociales. Sin embargo, cuando se analiza la titulación en su conjunto, dichas diferencias desaparecen. La conclusión, por tanto, es que la especialidad de ciencias en bachillerato confiere, únicamente, una ventaja al inicio de los estudios universitarios. También se ha confirmado que, en titulaciones sin apenas carga cuantitativa, el efecto de la especialidad en bachillerato no es, en general, una variable relevante para explicar el rendimiento académico en la universidad, es decir, que los resultados son similares con independencia de la especialidad de procedencia.ES

Coexistence of low vitamin D and high fibroblast growth factor-23 plasma levels predicts an adverse outcome in patients with coronary artery disease.

OBJECTIVE: Vitamin D and fibroblast growth factor-23 (FGF-23) are related with cardiovascular disorders. We have investigated the relationship of calcidiol (vitamin D metabolite) and FGF-23 plasma levels with the incidence of adverse outcomes in patients with coronary artery disease. METHODS: Prospective follow-up study of 704 outpatients, attending the departments of Cardiology of four hospitals in Spain, 6-12 months after an acute coronary event. Baseline calcidiol, FGF-23, parathormone, and phosphate plasma levels were assessed. The outcome was the development of acute ischemic events (any acute coronary syndrome, stroke, or transient ischemic attack), heart failure, or death. Cox regression adjusted for the main confounders was performed. RESULTS: Calcidiol levels showed a moderate-severe decrease in 57.3% of cases. Parathormone, FGF-23, and phosphate levels were increased in 30.0%, 11.5% and 0.9% of patients, respectively. Only 22.4% of patients had glomerular filtration rate<60 ml/min1.73 m2. After a mean follow-up was 2.15±0.99 years, 77 patients developed the outcome. Calcidiol (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.48-0.94; p = 0.021) and FGF-23 (HR = 1.13; 95% CI = 1.04-1.23; p = 0.005) plasma levels predicted independently the outcome. There was a significant interaction between calcidiol and FGF-23 levels (p = 0.025). When the population was divided according to FGF-23 levels, calcidiol still predicted the outcome independently in patients with FGF-23 levels higher than the median (HR = 0.50; 95% CI = 0.31-0.80; p = 0.003) but not in those with FGF-23 levels below this value (HR = 1.03; 95% CI = 0.62-1.71; p = 0.904). CONCLUSIONS: Abnormalities in mineral metabolism are frequent in patients with stable coronary artery disease. In this population, low calcidiol plasma levels predict an adverse prognosis in the presence of high FGF-23 levels

Likelihood of presenting a RP or RP + hypoacusis instead of a USH2 diagnosis in patients which carry a <i>USH2A</i> missense variant, comparing them with patients with an <i>USH2A</i> truncating variant, in addition to p.(Cys759Phe).

<p>Likelihood of presenting a RP or RP + hypoacusis instead of a USH2 diagnosis in patients which carry a <i>USH2A</i> missense variant, comparing them with patients with an <i>USH2A</i> truncating variant, in addition to p.(Cys759Phe).</p

Genotype of 46 Spanish families carrying the p.(Cys759Phe) pathogenic variant in compound heterozygous state or heterozygous carriers with other causative genes.

<p>Genotype of 46 Spanish families carrying the p.(Cys759Phe) pathogenic variant in compound heterozygous state or heterozygous carriers with other causative genes.</p

Phenotypic findings in 59 patients from 52 families carrying the p.(Cys759Phe) variant, classified by their genotype.

<p>Phenotypic findings in 59 patients from 52 families carrying the p.(Cys759Phe) variant, classified by their genotype.</p

Survival analysis.

<p>Kaplan-Meier survival curves were estimated for each event and the curves of the different groups were compared using the log-rank test. The three categories of patients are considered separately, and then in two new regroupings (Category A + B) and (Category B + C). Category A: p.(Cys759Phe) homozygous, Category B: compound heterozygous p.(Cys759Phe) + <i>USH2A</i> missense variant, and Category C: compound heterozygous p.(Cys759Phe) + <i>USH2A</i> truncating variant. X axis: age in years. Y axis: probability of survival. Graph 1. Survival curve: fraction of patients free of legal blindness due to VF<10° over time. Graph 2. Survival curve: fraction of patients free of cataracts over time. Graph 3. Survival curve: fraction of patients free of hypoacusis over time.</p