Agreement Between 18F-FDG PET/CT and Whole-Body Magnetic Resonance Compared With Skeletal Survey for Initial Staging and Response at End-of-Treatment Evaluation of Patients With Multiple Myeloma

PURPOSE: To compare the agreement between whole-body (WB) magnetic resonance (MR) imaging, 18F-FDG PET/CT, and skeletal survey (SS) in patients with multiple myeloma (MM) for diagnosis, initial staging, response evaluation, and early detection of complications. METHODS: This is a retrospective cohort study including MM patients who were diagnosed, treated, and followed in 2 institutions. These patients were studied with SS, WB-MR, and/or 18F-FDG PET/CT. We studied bone lesions by anatomical locations and analyzed the concordance between SS and a tomographic technique (WB-MR or 18F-FDG PET/CT) and between both tomographic techniques (WB-MR and PET/CT). RESULTS: Forty-four MM patients with a mean age of 62.6 years (range, 38-85 years) were included from January 2012 to February 2016. Whole-body MR and 18F-FDG PET/CT found more lesions than SS in every location except in the skull. Concordance between WB-MR and 18F-FDG PET/CT was either good or excellent in most of the locations and in plasmacytoma studies. However, WB-MR was better than 18F-FDG PET/CT in the study of complications (medullar compression and vascular necrosis). CONCLUSIONS: Our results suggest the study of MM patients should include WB-MR and/or 18F-FDG PET/CT, whereas SS is only useful for the skull. Whole-body MR and 18F-FDG PET/CT are complementary techniques, because both of them show good concordance in almost every location. It is still necessary to individualize the indication of each technique according to patient characteristics.None declare

Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome

Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction.

microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results: We have used an inducible endothelium-specific knock-in mouse model to address the role of miR-217 in vascular function and atherosclerosis. miR-217 reduced NO production and promoted endothelial dysfunction, increased blood pressure, and exacerbated atherosclerosis in proatherogenic apoE-/- mice. Moreover, increased endothelial miR-217 expression led to the development of coronary artery disease and altered left ventricular heart function, inducing diastolic and systolic dysfunction. Conversely, inhibition of endogenous vascular miR-217 in apoE-/- mice improved vascular contractility and diminished atherosclerosis. Transcriptome analysis revealed that miR-217 regulates an endothelial signaling hub and downregulates a network of eNOS (endothelial NO synthase) activators, including VEGF (vascular endothelial growth factor) and apelin receptor pathways, resulting in diminished eNOS expression. Further analysis revealed that human plasma miR-217 is a biomarker of vascular aging and cardiovascular risk. Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease.V.G. de Yébenes was supported by Ramón y Cajal grant RYC-2009-04503 and AECC foundation grant INVES18013GARC and by the Universidad Complutense de Madrid. S.M. Mur and A.R. Ramiro are supported by Centro Nacional de Investigaciones Cardiovasculares (CNIC) funding. A.R. Ramiro was supported by the Spanish Ministerio de Ciencia e Innovación (PID2019-107551RB-I00), the Spanish Ministerio de Economía, Industria y Competitividad (SAF2013-42767-R and SAF2016-75511-R), and the European Research Council StG BCLYM. M. Salaices was supported by the Ministerio de Ciencia e Innovación (SAF2016-80305P) and with J. Miguel Redondo by Instituto de Salud Carlos III (CIBER de Enfermedades Cardiovasculares, CB16/11/00286 and CB16/11/00264) and Comunidad de Madrid (B2017/BMD-3676). V.G. de Yébenes was supported by Ministerio de Ciencia e Innovación (PID2019-107551RB-I00). Further support was provided by the European Social Fund and the European Regional Development Fund “A Way to Build Europe.” The CNIC is supported by Ministerio de Ciencia, Innovacion y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Aging-Associated miR-217 Aggravates Atherosclerosis and Promotes Cardiovascular Dysfunction

microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results: We have used an inducible endothelium-specific knock-in mouse model to address the role of miR-217 in vascular function and atherosclerosis. miR-217 reduced NO production and promoted endothelial dysfunction, increased blood pressure, and exacerbated atherosclerosis in proatherogenic apoE-/- mice. Moreover, increased endothelial miR-217 expression led to the development of coronary artery disease and altered left ventricular heart function, inducing diastolic and systolic dysfunction. Conversely, inhibition of endogenous vascular miR-217 in apoE-/- mice improved vascular contractility and diminished atherosclerosis. Transcriptome analysis revealed that miR-217 regulates an endothelial signaling hub and downregulates a network of eNOS (endothelial NO synthase) activators, including VEGF (vascular endothelial growth factor) and apelin receptor pathways, resulting in diminished eNOS expression. Further analysis revealed that human plasma miR-217 is a biomarker of vascular aging and cardiovascular risk. Our results highlight the therapeutic potential of miR-217 inhibitors in aging-related cardiovascular disease.V.G. de Yébenes was supported by Ramón y Cajal grant RYC-2009-04503 and AECC foundation grant INVES18013GARC and by the Universidad Complutense de Madrid. S.M. Mur and A.R. Ramiro are supported by Centro Nacional de Investigaciones Cardiovasculares (CNIC) funding. A.R. Ramiro was supported by the Spanish Ministerio de Ciencia e Innovación (PID2019-107551RB-I00), the Spanish Ministerio de Economía, Industria y Competitividad (SAF2013-42767-R and SAF2016-75511-R), and the European Research Council StG BCLYM. M. Salaices was supported by the Ministerio de Ciencia e Innovación (SAF2016-80305P) and with J. Miguel Redondo by Instituto de Salud Carlos III (CIBER de Enfermedades Cardiovasculares, CB16/11/00286 and CB16/11/00264) and Comunidad de Madrid (B2017/BMD-3676). V.G. de Yébenes was supported by Ministerio de Ciencia e Innovación (PID2019-107551RB-I00). Further support was provided by the European Social Fund and the European Regional Development Fund “A Way to Build Europe.” The CNIC is supported by Ministerio de Ciencia, Innovacion y Universidades, and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Anales de Edafología y Agrobiología Tomo 42 Número 5-6

Suelos. Retención de Parathión en Bentonitas Homoiónicas. II. Isotermas de retención y magnitudes termodinámicas relacionadas, por F. del Rey Bueno, E. González Pradas, C. Valenzuela Calahorro y J. D. López González.-- Formaciones edáficas de la región de Ocaña (Toletlo ). l. Entisoles., por José Gumuzzio Fernández y José B. Alvarez Martín.-- Caracterización hidrodinámica de un suelo de olivar. Fundamento teórico y métodos experimentales, por F. Moreno, G. Vachaud y J. Martín Aranda.-- Niveles de influencia de la vegetación en los horizontes superficiales de los suelos. II. Características morfológicas, análisis granulométrico, por Hoyos de Castro, A., Hernando Costa, J., Egido Rodríguez, J. A. y de la Cruz Caravaca, M. T.-- Estudio geológico e identificación de minerales interestratificados clorita-esmectita, mediante sorción interlaminar de aminas. Triásico de la cordillera iberia. l. por M. Doval, M. Rodas, A. Ruiz Amil y F. Aragón.—Fertilidad del Suelo. Niveles foliares de las plantaciones de aguacates de las Islas Canarias occidentales, por V. García, A. Díaz, M. Altares, J. J. Bravo Rodríguez y M. Fernández.-- Caracterización y valor fertilizante de los purines de vacuno en Galicia.t. por M. C. Leiros de la Peña, M. C. Villar Celorio, A. Cabaneiro, T. Carballas, F. Díaz-Fierros, F. Gil Sotres y C. Gómez lbarlucea.—Nutrición y Fisiología Vegetal. Efecto del azufre, nitrógeno y Rhizobium sobre la cosecha, nodulación y contenido de nutrientes en Phaseolus Vulgaris, por Lluch, C., Campos, J.A. y Ligero, F.-- Influencia de la presión osmótica sobre podredumbre apical del tomate (Lycopersicum esculentum), por Ma P. Sánchez Conde.-- Efecto de las giberelinas producidas por Rhizobium Meliloti en la nodulación de alfalfa (Medicago sativa L.), por Lluc, C., Ligero, F. y Olivares, J.-- Bases para el diagnóstico del exceso de boro en limonero, por A. León, A. Torrecillas, F. del Amor y M.a R. Monllor.-- Influencia del hospedador en la infección de las raíces de leguminosas por Rhizobium por M. A. Herrera, L. Mejías, E. Martínez-Molina y J. Olivares.-- Efectos de la irradiación con UV cercano sobre la evolución del contenido de apigenina y quercetol en ononis spinosa L., por J. Baztan.-- Composición mineral y estudio estructural de los tejidos sanos y afectados de podredumbre apical en dos variedades de tomate, (Lycopersicum Esculentum L.), por Ma P. Sánchez Conde y Ma R. de Felipe.—Trabajos recapitulativos. Aplicación de la isoterma de langmuir al estudio de las interacciones sólido-disolución en suelo, por M. Suárez y J. Sánchez-Andreu .-- Evaluación de la erosión hídrica de los suelos, por P. Sanroque, J. L. Rubio y J. Sánchez.-- Nota prioritaria. Criterios ecológicos en el uso de plaguicidas, por Eugenio Laborda.-- NotasPeer reviewe

Fluorescent bicolour sensor for low-background neutrinoless double β decay experiments

Observation of the neutrinoless double β decay is the only practical way to establish that neutrinos are their own antiparticles. Because of the small masses of neutrinos, the lifetime of neutrinoless double β decay is expected to be at least ten orders of magnitude greater than the typical lifetimes of natural radioactive chains, which can mimic the experimental signature of neutrinoless double β decay. The most robust identification of neutrinoless double β decay requires the definition of a signature signal—such as the observation of the daughter atom in the decay—that cannot be generated by radioactive backgrounds, as well as excellent energy resolution. In particular, the neutrinoless double β decay of Xe could be established by detecting the daughter atom, Ba, in its doubly ionized state. Here we demonstrate an important step towards a ‘barium-tagging’ experiment, which identifies double β decay through the detection of a single Ba ion. We propose a fluorescent bicolour indicator as the core of a sensor that can detect single Ba ions in a high-pressure xenon gas detector. In a sensor made of a monolayer of such indicators, the Ba dication would be captured by one of the molecules and generate a Ba-coordinated species with distinct photophysical properties. The presence of such a single Ba-coordinated indicator would be revealed by its response to repeated interrogation with a laser system, enabling the development of a sensor able to detect single Ba ions in high-pressure xenon gas detectors for barium-tagging experiments.We also acknowledge support from the following agencies and institutions: the European Research Council (ERC) under Advanced Grant 339787-NEXT; the Ministry of Science and Innovation of Spain and FEDER under grants FIS2014-53371-C04, FIS2016-76163-R, MAT2016-78293-C6-5-R, MINECO/FEDER CT2016-80955-P, CTQ2016-80375-P and CTQ2014-51912-REDC; Interred PCTEFA V-A Spain/France/Andorra Program (EFA 194/16/TNSI); the Basque Government (GV/EJ) under grants IT-1346-19 and IT-1180-19; andAgencia de Ciencia y Tecnología de la Región de Murcia (19897/GERM/15). The authors also thank the SGI/IZO-SGIker UPV/EHU, Fundación Séneca and DIPC for computational and analytical resources