Cambios del estado nutricional y citocinas en pacientes alcohólicos : valor clínico y pronóstico

El alcoholismo constituye un problema sanitario de vital importancia, que puede repercutir a cualquier nivel del organismo afectando, entre otros, al estado nutricional. Por otro lado, cada vez es mayor la evidencia de que en el alcohólico existe una situación inflamatoria subyacente. Tanto la malnutrición como la situación proinflamatoria pueden tener relación con la supervivencia en el paciente con hepatopatía alcohólica. Objetivos: analizar la mortalidad global a largo plazo y las causas de muerte del paciente alcohólico ingresado en Medicina Interna; analizar la relación del estado nutricional al ingreso y sus cambios a los seis meses con mortalidad a medio plazo; analizar qué factores, función hepática, consumo de alcohol, hábitos alimenticios, reacción inflamatoria- pueden condicionar el estado nutricional de estos pacientes; analizar el efecto de la abstinencia alcohólica sobre los cambios en el estado nutricional. Pacientes y método: 240 pacientes alcohólicos y 130 controles sanos, sin diferencias en las características basales. Se recogió datos epidemiológicos, tiempo y cuantía de consumo, se realizó medidas antropométricas, dinamometría, valoración del estado nutricional empleando una escala de valoración nutricional subjetiva y densitometría con composición corporal total (a 210 pacientes y 80 controles). Esta técnica se repitió en una segunda valoración a 100 pacientes. Resultados: mediana de seguimiento: 39 meses, fallecieron 91 pacientes (edad media 54,9 +/- 10,89). Causas principales de muerte: insuficiencia hepática, cáncer y cardiovascular. Los pacientes tenían una masa magra más baja que los controles en todos los compartimentos corporales analizados (p < 0,05 en todos los casos, salvo en tronco), sin diferencias en la masa grasa. Los niveles de citocinas estaban más altos en pacientes que en controles en la situación basal (p< 0,05 en todos los casos, salvo IL-6) y en la segunda determinación. Una masa magra disminuída en brazos se asoció a mayor mortalidad, pero la masa grasa en la primera determinación no mostró valor pronóstico alguno. Una peor valoración nutricional subjetiva se asoció a mayor mortalidad, así como la presencia de cirrosis hepática y peor puntuación en la escala de Child. Niveles elevados de IL-4 se relacionaron con mayor mortalidad. Al realizar la segunda evaluación a los 6 meses y comparar los datos con la primera determinación se encontró que un descenso de masa magra en la práctica totalidad de los compartimentos analizados (salvo en brazo derecho) se asocia a mayor mortalidad y que los pacientes que fallecen ganan masa grasa. Se encontró niveles de citocinas elevados en los pacientes que fallecían por insuficiencia hepática, cáncer y causa cardiovascular en relación con los controles e incluso con los supervivientes cuando la causa de muerte era la cardiovascular. Los pacientes que dejaban de beber, tenían una mejoría global del estado nutricional. Conclusiones: mortalidad elevada (40%) a edades tempranas (55 años); las causas principales de muerte derivan de insuficiencia hepática, cáncer y cardiovascular con niveles de citocinas significativamente más elevados que en los controles y mostraban además una tendencia a estar más altos que en los enfermos supervivientes; las citocinas inflamatorias estaban elevadas y esta elevación tendía a relacionarse con la pérdida de masa magra a lo largo del tiempo; las citocinas persistían altas en la segunda determinación e incluso en los pacientes abstinentes, lo que sugiere que el alcoholismo puede ser considerado como una "enfermedad inflamatoria"; en el alcohólico existe una malnutrición de tipo obeso y la pérdida de masa magra es la variable mejor relacionada con la supervivencia; en la malnutrición, caracterizada por una pérdida de masa magra e incremento relativo de masa grasa influyen parámetros relacionados con la función hepática, citocinas (IL-6 e IL-8) y peores hábitos alimenticios; el índice de masa corporal es de poca utilidad en estos pacientes; el hecho de continuar bebiendo se asocia a una tendencia, por lo general no significativa, de ganancia de masa grasa

El Homeschooling.

El presente documento contempla la percepción que tienen 29 encuestados del CEIPS Acaymo – La Candelaria sobre el Homeschooling. En las respuestas se han encontrado diferencias estadísticamente significativas en cuanto a la percepción y/o aceptación de este movimiento pedagógico alternativo. Para llevar a cabo la investigación se ha utilizado un cuestionario, a través del cual se han recogido datos suficientes para conseguir los objetivos establecidos.This document examines how 29 survey respondents from CEIPS Acaymo – La Candelaria have about Homeschooling. In the answers we have found responses regarding the perception and/or acceptance of this alternative pedagogical movement. This research was carried out by means of a questionnaire which enabled sufficient data to be gathered in order to achieve the established aims

Apolipoprotein C-III is linked to the insulin resistance and beta-cell dysfunction that are present in rheumatoid arthritis

Background: Insulin resistance and beta-cell dysfunction are manifestations of rheumatoid arthritis (RA). Apolipoprotein C-III (ApoC3) has been associated with such insulin resistance and beta-cell dysfunction in the general population. Our purpose was to study whether ApoC3 is also related to the insulin resistance and beta-cell dysfunction that are present in patients with RA. Methods: Three hundred thirty-eight non-diabetic patients with RA who had a glycemia lower than 110 mg/dl were recruited. Insulin, C-peptide, and ApoC3 were assessed. Insulin resistance and beta-cell function were calculated using the Homeostasis Model Assessment (HOMA2) indices. A multivariable regression analysis was performed to study the relationship of ApoC3 with those molecules and indices adjusting for classic factors associated with insulin resistance that included glucocorticoids. Results: ApoC3 was related to significant higher levels of circulating insulin (beta coef. 0.37 [95%CI 0.01–0.73] μU/ml, p = 0.044) and C-peptide (beta coef. 0.13 [95%CI 0.05–0.22] ng/ml, p = 0.003), and higher insulin resistance —HOMA2- IR— (beta coef. 0.05 [95%CI 0.00–0.09], p = 0.041) and beta-cell dysfunction —HOMA2-%B— (beta coef. 2.94 [95%CI0.07–5.80], p = 0.044) indices. This was found after a fully multivariable analysis that included, among others, prednisone intake and the classic factors associated with carbohydrate metabolism such as triglycerides, waist circumference, and obesity. Conclusion: ApoC3, insulin resistance, and beta-cell dysfunction are independently associated in patients RA.This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdireccion General de Evaluacion y Fomento de la Investigacion, Plan Estatal de Investigacion Cientifica y Tecnica y de Innovacion 2013–2016 and by Fondo Europeo de Desarrollo Regional—FEDER—(Fondo de Investigaciones Sanitarias, PI17/00083

Apolipoprotein C-III in patients with systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) has been associated with atherosclerotic cardiovascular disease (CV) and an altered lipid profile. High levels of apolipoprotein C-III (ApoC3) are associated with elevated triglyceride levels and an increased risk of CV. In the present study, we aimed to study circulating ApoC3 in patients with SLE and describe its relationship with the manifestations of the disease. Methods: This is a cross-sectional study that included 186 patients with SLE. Disease-related data, CV comorbidity, full lipid profile, and serum levels of ApoC3 were assessed. A multivariable regression analysis was performed to study how ApoC3 was related to SLE features. Results: Classic CV risk factors were significantly and strongly associated with circulating ApoC3. After a fully multivariable analysis that included classic CV risk factors and lipid profile molecules, SLICC damage (beta coef. 0.10 [95% CI 0.02?0.19] mg/dl, 0.020) and Katz severity (beta coef. 0.11 [95% CI 0.03-0.19] mg/dl, p = 0.011) indices and SLEDAI activity score (beta coef. 0.05 [95% CI 0.05-0.08] mg/dl, p = 0.004) were all independently associated with higher levels of circulating ApoC3. Conclusion: Among SLE patients, disease activity, severity, and disease damage are independently associated with higher ApoC3 serum levels.Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional—FEDER—(Fondo de Investigaciones Sanitarias, PI17/00083)

Vascular endothelial growth factor and its soluble receptor in systemic lupus erythematosus patients

Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Its soluble receptor (sVEGFR) is a potent VEGF antagonist. Systemic lupus erythematosus (SLE) is an autoimmune disease with a diverse array of clinical manifestations that affect virtually any organ. We aimed to analyze the relationship of VEGF and sVEGFR with SLE disease-related features including disease activity, damage, and severity. Serum levels of VEGF165 isoform and sVEGFR (receptor 1) were assessed in 284 well-characterized patients with SLE. Linear regression analysis was performed to analyze the relationship of disease characteristics with both VEGF and sVEGFR. Patients with a disease damage index (SLICC score) equal to or greater than 1 had significantly elevated serum levels of VEGF and sVEGFR. Regarding disease-specific features, musculoskeletal manifestations were the disease feature most commonly associated with the upregulation of both VEGF and sVEGFR. SLE disease damage is associated with higher levels of VEGF and sVEGFR.Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional—FEDER—(Fondo de Investigaciones Sanitarias, PI20/00084)

Key molecules of triglycerides pathway metabolism are disturbed in patients with systemic lupus erythematosus

Background: Elevated triglycerides or triglyceride-rich lipoproteins are an additional cause of cardiovascular (CV) disease. Given that patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CV disease and show an altered lipid profile, our objective was to study whether three molecules that play a central role in the triglyceride metabolism: apolipoprotein C-III (ApoC3), angiopoietin-like protein 4 (ANGPLT4), and lipoprotein lipase (LPL) differ between SLE patients and controls, and how they are related to disease characteristics, including disease damage. Methods: Cross-sectional study that included 347 women, 185 of them diagnosed with SLE and 162 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in SLE patients and controls. A multivariable analysis was performed to assess whether ANGPTL4, ApoC3 and LPL molecules differ between patients and controls and to study their relationship with SLE disease damage. Results: After fully multivariable analysis that included classic CV risk factors, and the modifications that the disease itself produces over the lipid profile, it was found that ApoC3 was significantly lower (beta coef. -1.2 [95%CI -1.6- -0.8) mg/dl, <0.001), and ANGPTL4 (beta coef. 63 [95%CI 35-90] ng/ml, <0.001) and LPL (beta coef. 79 [95%CI 30-128] ng/ml, p=0.002) significantly higher in patients with SLE compared to controls. Disease damage score was significantly and independently associated with higher serum levels of LPL (beta coef. 23 [95%CI 10-35] ng/ml, p=0.001). Mediation analysis suggested that the relationship between disease damage and LPL was direct and not mediated by ApoC3 or ANGPLT4. Conclusion: The ApoC3, ANGPLT4 and LPL axis is disrupted in patients with SLE. Disease damage explains this disturbance.Funding: This work was supported by a grant to IF-A from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Cientı́fica y Técnica y de Innovación 2013-2016 and by Fondo Europeo de Desarrollo Regional - FEDER - (Fondo de Investigaciones Sanitarias, PI17/00083)

Sex Differences in Multimorbidity, Inappropriate Medication and Adverse Outcomes of Inpatient Care : MoPIM Cohort Study

There is no published evidence on the possible differences in multimorbidity, inappropriate prescribing, and adverse outcomes of care, simultaneously, from a sex perspective in older patients. We aimed to identify those possible differences in patients hospitalized because of a chronic disease exacerbation. A multicenter, prospective cohort study of 740 older hospitalized patients (≥65 years) was designed, registering sociodemographic variables, frailty, Barthel index, chronic conditions (CCs), geriatric syndromes (GSs), polypharmacy, potentially inappropriate prescribing (PIP) according to STOPP/START criteria, and adverse drug reactions (ADRs). Outcomes were length of stay (LOS), discharge to nursing home, in-hospital mortality, cause of mortality, and existence of any ADR and its worst consequence. Bivariate analyses between sex and all variables were performed, and a network graph was created for each sex using CC and GS. A total of 740 patients were included (53.2% females, 53.5% ≥85 years old). Women presented higher prevalence of frailty, and more were living in a nursing home or alone, and had a higher percentage of PIP related to anxiolytics or pain management drugs. Moreover, they presented significant pairwise associations between CC, such as asthma, vertigo, thyroid diseases, osteoarticular diseases, and sleep disorders, and with GS, such as chronic pain, constipation, and anxiety/depression. No significant differences in immediate adverse outcomes of care were observed between men and women in the exacerbation episode

Role of rare earth sites and vacancies in the anomalous compression of modulated scheelite tungstates

X-ray powder diffraction experiments at high pressures combining conventional sources and synchrotron radiation, together with theoretical simulations have allowed us to study the anomalous compression of the entire α-RE2(WO4)3 (RE = La-Ho) family with modulated scheelite structure (α phase). The investigated class of materials is of great interest due to their peculiar structural behavior with temperature and pressure, which is highly sought after for specialized high-tech applications. Experimental data were analyzed using full-profile refinements and were complemented with computational methods based on density functional theory (DFT) total energy calculations for a subset of the samples investigated. An unusual change in the compression curves of the lattice parameters a, c, and β was observed in both the experiments and theoretical simulations. In particular, in all the studied compounds the lattice parameter a decreased with pressure to a minimum value and then increased upon further compression. Pressure evolution of the experimental x-ray diffraction (XRD) patterns and cell parameters is correlated with the ionic radius of the rare earth element: (1) the lighter La-Nd tungstates underwent two phase transitions, and both transition pressures decreased as the rare earth's ionic radius increased. The XRD patterns of the first high pressure phase could be indexed with propagation vectors parallel to the a axis (tripling the unit cell). At higher pressures, the lattice parameters for the second phase (referred to as the preamorphous phase) showed little variation with pressure. (2) The heavier tungstates, from Sm to Dy, undergo a transition to the preamorphous phase without any intermediate phase. The reversibility of both phase transitions was investigated. DFT calculations support this unusual response of the crystal structures under pressure and shed light on the structural mechanism of negative linear compressibility (NLC) and the resulting softening. The pressure dependence of the structural modifications is related to tilting, along with small elongation and alignment, of the WO2−4 tetrahedrons. These changes correlate with those in the alternating RE…RE…RE chains and blocks of cationic vacancies arranged along the a axis. Possible stacking defects, which emerge between them, helped to explain this anomalous compression and the pressure induced amorphization. Such mechanisms were compared with other ferroelastic families of molybdates, niobates, vanadates, and other compounds with similar structural motifs classified as having “hinge frames.

Predicting Clinical Outcome with Phenotypic Clusters in COVID-19 Pneumonia: An Analysis of 12,066 Hospitalized Patients from the Spanish Registry SEMI-COVID-19

(1) Background: Different clinical presentations in COVID-19 are described to date, from mild to severe cases. This study aims to identify different clinical phenotypes in COVID-19 pneumonia using cluster analysis and to assess the prognostic impact among identified clusters in such patients. (2) Methods: Cluster analysis including 11 phenotypic variables was performed in a large cohort of 12,066 COVID-19 patients, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish Society of Internal Medicine (SEMI)-COVID-19 Registry. (3) Results: Of the total of 12,066 patients included in the study, most were males (7052, 58.5%) and Caucasian (10,635, 89.5%), with a mean age at diagnosis of 67 years (standard deviation (SD) 16). The main pre-admission comorbidities were arterial hypertension (6030, 50%), hyperlipidemia (4741, 39.4%) and diabetes mellitus (2309, 19.2%). The average number of days from COVID-19 symptom onset to hospital admission was 6.7 (SD 7). The triad of fever, cough, and dyspnea was present almost uniformly in all 4 clinical phenotypes identified by clustering. Cluster C1 (8737 patients, 72.4%) was the largest, and comprised patients with the triad alone. Cluster C2 (1196 patients, 9.9%) also presented with ageusia and anosmia; cluster C3 (880 patients, 7.3%) also had arthromyalgia, headache, and sore throat; and cluster C4 (1253 patients, 10.4%) also manifested with diarrhea, vomiting, and abdominal pain. Compared to each other, cluster C1 presented the highest in-hospital mortality (24.1% vs. 4.3% vs. 14.7% vs. 18.6%; p 20 bpm, lower PaO2/FiO2 at admission, higher levels of C-reactive protein (CRP) and lactate dehydrogenase (LDH), and the phenotypic cluster as independent factors for in-hospital death. (4) Conclusions: The present study identified 4 phenotypic clusters in patients with COVID-19 pneumonia, which predicted the in-hospital prognosis of clinical outcomes