Evaluation of endothelial function and subclinical atherosclerosis in patients with HIV infection

The aim of this study was to analyse the association between human immunodefciency virus (HIV) related clinical and analytical parameters and the presence of subclinical atherosclerosis as well as endothelial dysfunction. This was a prospective cohort study of HIV-positive patients who underwent intima media thickness (IMT) determination and coronary artery calcium scoring to determine subclinical atherosclerosis. To detect endothelial dysfunction, the breath holding index, fow-mediated dilation and the concentration of endothelial progenitor cells (EPCs) were measured. Patients with an IMT? 0.9 mm had an average of 559.3 ± 283.34 CD4/?l, and those with an IMT< 0.9 mm had an average of 715.4 ± 389.92 CD4/?l (p= 0.04). Patients with a low calcium score had a signifcantly higher average CD4 cell value and lower zenith viral load (VL) than those with a higher score (707.7 ± 377.5 CD4/?l vs 477.23 ± 235.7 CD4/?l (p= 0.01) and 7 ×?¬104 ± 5 ×?¬104 copies/ml vs 23.4 × 104 ± 19 × 104 copies/ml (p= 0.02)). The number of early EPCs in patients with a CD4 nadir< 350/ µl was lower than that in those with a CD4 nadir? 350 (p= 0.03). In HIV-positive patients, low CD4 cell levels and high VL were associated with risk of developing subclinical atherosclerosis. HIV patients with CD4 cell nadir < 350/µl may have fewer early EPCs

XIII Reunión Post-ECTRIMS : revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (I)

Introducción: Desde hace más de una década, tras el congreso ECTRIMS, se celebra en España la reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) de toda España se reúnen para revisar las principales novedades presentadas en el ECTRIMS (en esta ocasión, celebrado junto con el ACTRIMS). Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias que tuvieron lugar en la reunión Post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 de forma virtual. Desarrollo. En esta primera parte se incluyen los últimos resultados acerca del impacto del ambiente y el estilo de vida sobre el riesgo de EM y su curso clínico, y el papel de la epigenética y los factores genéticos sobre estos procesos. Se discuten los hallazgos en investigación preclínica y clínica sobre los subtipos de linfocitos identificados, y la implicación de los folículos linfoides y la afectación meníngea en la enfermedad. Los cambios en la estructura cerebral se abordan a nivel microscópico y macroscópico, incluyendo resultados de técnicas de imagen de alta resolución. También se presentan los últimos avances sobre biomarcadores para el diagnóstico y el pronóstico de la EM, y sobre la afectación del microbioma en estos pacientes. Por último, se esbozan los resultados de registros de pacientes sobre el impacto de la COVID-19 en los pacientes con EM. Conclusiones: Ha habido nuevos datos sobre factores de riesgo de la EM, impacto de la EM a nivel celular y estructural, papel del microbioma en la enfermedad, biomarcadores y la relación entre COVID-19 y EM.Introduction. For more than a decade, following the ECTRIMS Congress, the Post-ECTRIMS Meeting has been held in Spain, where neurologists with expertise in multiple sclerosis (MS) from all over the country meet to review the most relevant latest developments presented at the ECTRIMS congress (on this occasion held together with ACTRIMS). Aim. This article, published in two parts, summarises the presentations that took place at the Post-ECTRIMS Meeting, held online on 16 and 17 October 2020. Development. This first part includes the latest results regarding the impact of the environment and lifestyle on risk of MS and its clinical course, and the role of epigenetics and genetic factors on these processes. Findings from preclinical and clinical research on the lymphocyte subtypes identified and the involvement of lymphoid follicles and meningeal involvement in the disease are discussed. Changes in brain structure are addressed at the microscopic and macroscopic levels, including results from high-resolution imaging techniques. The latest advances on biomarkers for the diagnosis and prognosis of MS, and on the involvement of the microbiome in these patients are also reported. Finally, results from patient registries on the impact of COVID-19 in MS patients are outlined. Conclusions. There have been new data on MS risk factors, the impact of MS at the cellular and structural level, the role of the microbiome in the disease, biomarkers, and the relationship between COVID-19 and MS

XIII Reunión Post-ECTRIMS: Revisión de las novedades presentadas en el Congreso ECTRIMS 2020 (II)

Introducción: Desde hace más de una década, tras el Congreso ECTRIMS, se celebra en España la reunión post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) se reúnen para revisar las novedades presentadas en el ECTRIMS. Objetivo: En el presente artículo, publicado en dos partes, se resumen las ponencias de la reunión post-ECTRIMS, celebrada los días 16 y 17 de octubre de 2020 virtualmente. Desarrollo: En esta segunda parte se destaca la importancia del género y la edad en la compresión de la patología de la enfermedad y la optimización de su manejo. Se exponen los avances realizados en la EM pediátrica desde un punto de vista neuropsicológico y de neuroimagen. Por su parte, cobran especial protagonismo los hallazgos que contribuyen a realizar un enfoque del tratamiento más personalizado y a elegir la mejor estrategia de tratamiento (farmacológica y no farmacológica) para cada paciente. De igual forma, se abordan los resultados relacionados con las estrategias posibles que promuevan la remielinización. Aunque no hay grandes avances en el tratamiento de formas progresivas, se destacan algunos métodos cuantitativos para la clasificación de estos pacientes. Además, se incluyen los resultados sobre herramientas potenciales de evaluación y tratamiento de los déficits cognitivos, y algunos aspectos relevantes observados en el espectro de los trastornos de la neuromielitis óptica. Por último, se detallan los resultados de las ponencias consideradas como noticias de última hora en el ECTRIMS-ACTRIMS. Conclusiones: Se presentaron avances principalmente sobre el conocimiento de la EM pediátrica, las estrategias de remielinización y la evaluación cognitiva en la EM.Introduction. For more than a decade, after the ECTRIMS Congress, Spain has hosted the Post-ECTRIMS meeting, where neurologists with expertise in multiple sclerosis (MS) meet to review the new developments presented at the ECTRIMS. Aim. This article, published in two parts, summarises the presentations of the post-ECTRIMS meeting, held online on 16 and 17 October 2020. Development. This second part highlights the importance of gender and age in understanding the pathology of the disease and optimising its management. The advances made in paediatric MS, from a neuropsychological and neuroimaging point of view, are presented. In turn, special attention is paid to the findings that contribute to a more personalised approach to therapy and to choosing the best treatment strategy (pharmacological and non-pharmacological) for each patient. Similarly, results related to possible strategies to promote remyelination are addressed. Although there are no major advances in the treatment of progressive forms, some quantitative methods for the classification of these patients are highlighted. In addition, the study also includes results on potential tools for assessment and treatment of cognitive deficits, and some relevant aspects observed in the spectrum of neuromyelitis optica disorders. Finally, the results of the papers considered as breaking news at the ECTRIMS-ACTRIMS are detailed. Conclusions. Most of the advances presented were related to the knowledge of paediatric MS, remyelination strategies and cognitive assessment in MS

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

La luz en la Quinta del Sordo : estudio de las formas y cotidianidad

Esta investigación se centra, concretamente en el estudio de las catorce pinturas, las llamadas "Pinturas Negras" que Goya pintó en la Quinta del Sordo, en un periodo de tiempo concreto de 1820 a 1823, la Quinta era una casa de recreo que el pintor compró a la orilla del río Manzanares con el fin de pasar allí un periodo, casi al final de su vida en un clima de descanso y disfrute personal. Además he ahondado en todo lo que se refiere a la casa con la idea de aproximarnos mejor a la situación y el momento en que realiza las pinturas para entender mejor lo que rodea y envuelve a las Pinturas Negras. En primer lugar he trabajado para dar una visión exhaustiva de las pinturas una a una, concentrándome en el estudio de las pinturas en su estado original antes de destruir la casa, cuando fueron fotografíadas por el fotógrafo de nacionalidad francesa J:Laurent. También realizó un estudio sobre las pinturas tal y como se encuentran actualmente en el Mueseo del Prado, resultado del trabajo que realizó el pintor y restaurador Salvador Martínez Cubells cuando le encomendaron la dificil tarea de sacar las pinturas de los muros de la casa y trasladarlas a tela. La forma o estructura a seguir en el desarrollo de esta investigación la dividiría en cuatro partes o bloques: Antes de entrar en el cuerpo de la tesis se expone la vida del pintor a modo de Currículo Vitae y se reproduce su escrito sobre las enseñanzas en las Academias de Bellas Artes. En primer lugar, realizó un análisis plástico según mis impresiones personales sobre las pinturas en su estado original fotografiadas por J.Laurent y siguiendo el mismo esquema de trabajo sobre las pinturas en su estado actual al ser trasladadas de las paredes a telas por Salvador Martínez Cubells. Analizando la luz la composición, el color y la expresividad. Además, contrasto en tercer lugar diferencias u similitudes entre las pinturas en su estado original y su estado actual.También hago hincapié en la ubicación de las pinturas en el Museo del Prado y la situación original de las pinturas en la casa. Por último y en cuarto lugar llegamos al proceso de realización de la maqueta que nos da una idea más próxima a cómo era y estaban dispuestas las pinturas en las habitaciones de la casa, haciendo una recreación que iría de lo real a lo imaginari

UGT2B7_-161C>T polymorphism is associated with lamotrigine concentration-to-dose ratio in a multivariate study

Lamotrigine (LTG) is metabolized by UGT1A4 but UGT2B7 also contributes to its glucuronidation. The aim of this study was to determine whether UGT2B7_− 161C>T and UGT2B7_372A>G polymorphisms contribute to the intersubject variability in LTG concentration-to-dose ratio (LTG-CDR) in epileptic patients. Fifty-three white epileptic patients attending the Neuropediatric and Neurology Services at the Marqués de Valdecilla University Hospital, in whom LTG serum concentration was to be measured for pharmacokinetic monitoring, were selected according to predefined criteria for LTG-CDR evaluation. All patients had at least one steady-state LTG serum concentration obtained before the first dose in the morning. Patients were classified in 3 groups of comedication: (1) LTG in combination with metabolism-inducer anticonvulsants (n = 22), (2) LTG in combination with valproate (n = 13), and (3) LTG as monotherapy (n = 16) or in combination with valproate and inducers (n = 2). Genotypes were determined by Applied Biosystems Genotyping Assays with TaqMan probes. A significant association was found between LTG-CDR and UGT2B7_−161C>T polymorphism (P = 0.021) when patient age and concomitant antiepileptic drugs were taken into account. Comedication explained 70% of the LTG-CDR variability, patient age 24%, and UGT2B7_−161C>T 12%. In contrast, a significant association between LTG-CDR and this polymorphism was not found in the bivariate study when age and comedication groups were not considered. A significant association between UGT2B7_372A>G and LTG-CDR was not found in the bivariate or the multivariate studies. UGT2B7_−161C>T polymorphism is significantly associated with LTG-CDR when comedication with other antiepileptic drugs and patient age are taken into account in a multivariate analysis.Peer reviewe

UGT2B7_-161C>T polymorphism associated with lamotrigine concentration-to-dose ratio

Trabajo presentado al 9th Congress of the European Association for Clinical Pharmacology and Therepeutics celebrado en edimburgo del 12 al 15 de julio de 2009.UGT2B7 contributes to lamotrigine metabolism. The aim of this study was to analyze if there was an association between UGT2B7_-161C>T polymorphism and lamotrigine concentration-to-dose ratio (CDR) in epileptic patients. Fifty-four caucasian epileptic patients attending Neuropediatrics and Neurology Services at the Marqués de Valdecilla University Hospital, in whom lamotrigine serum concentration was to be measured for pharmacokinetic monitoring, were selected according to predefined pharmacokinetic criteria. All patients had at least one steady-state lamotrigine serum concentration obtained before the first dose in the morning. Patients were classified in three groups of co-treatment: (i) lamotrigine in combination with metabolism-inducer anticonvulsants (n = 22), (ii) lamotrigine in combination with valproate (n = 13) and (iii) lamotrigine in monotherapy or in combination with valproate and inducers (n = 16). Genotypes were determined by Applied Biosystems Genotyping Assays with TaqMan probes. The association between lamotrigine CDR and UGT2B7_-161C>T was evaluated by analysis of covariance considering the group of co-treatment and the patient age. A significant association was found between lamotrigine CDR and UGT2B7_-161C>T polymorphism (P = 0.006); lamotrigine CDR was also associated with co-treatment group (P T polymorphism might explain, at least in part, inter-patient variability in lamotrigine CDR and it should be considered besides co-treatment and patient age in the individualization of lamotrigine dose. They also show that multivariable study may be necessary in order to unmask the influence of genetic factors.Peer Reviewe

ABCB1_3435C>T AND ABCB1_2677G>T polymorphisms and pharmacoresistance of epilepsy: differences between children and adults

Trabajo presentado al 9th Congress of the European Association for Clinical Pharmacology and Therepeutics celebrado en edimburgo del 12 al 15 de julio de 2009.Children and adults differ in the kind of epilepsy and in the anticonvulsants used. The aim of this study was to analyze the association between ABCB1_3435C>T and ABCB1_2677G>T polymorphisms and pharmacorresistance in epileptic patients stratified into children and adults groups. Two hundred and eighty-nine caucasian epileptic patients, 80 children (£12 years) and 209 adults (>12 years), attending Neuropediatrics and Neurology Services at the Marqués de Valdecilla University Hospital were selected when they had either drug resistance (occurrence of at least four seizures over the year before recruitment with trials of more than three appropriate antiepileptic drugs at appropriate doses) or drug responsiveness (complete freedom from seizures for at least a year). Samples were genotyped by Applied Biosystems Genotyping Assays with TaqMan probes. Association was evaluated by stratified bivariate analysis using contingency tables. The pharmacoresistance risk in patients with the ABCB1_3435TT genotype was lower than in those with the CC genotipe in adults (OR: 0.40, 95%CI: 0.19-0.86, P = 0.019) but higher in children (OR: 4.22, 95%CI: 0.98-18.12), with a significant interaction between age and polymorphism (P = 0.015). Furthermore, the pharmacoresistance risk in patients with the ABCB1_2677TT genotype was lower than in those with the GG genotipe in adults (OR: 0.41, 95%CI: 0.18-0.92) but higher in children (OR: 4.17, 95%CI: 1.13-15.33), with a significant interaction between age and polymorphism (P = 0.006). ABCB1_3435TT and ABCB1_2677TT genotypes are associated with lower risk of pharmacoresistance than CC or GG genotypes in epileptic adults but with a higher risk in children.Peer Reviewe

ABCB1_3435C>T polymorphism and pharmacoresistance of epilepsy: differences related with the etiology of epilepsy

Trabajo presentado al 13th Congress of the EFNS celebrado en Florencia del 12 al 15 de septiembre de 2009.The etiology of epilepsy is a factor associated with differences in response to anticonvulsants and control of epilepsy. The aim of this study was to analyze the association between ABCB1_3435C>T and ABCB1_2677G>T polymorphisms and pharmacoresistance in patients stratified by epilepsy etiology. Caucasian epileptic patients (n=289) attending Neuropaediatrics and Neurology Services at the Marqués de Valdecilla University Hospital were selected when they had either drug resistance (occurrence of at least four seizures over the year before recruitment with trials of more than three appropriate antiepileptic drugs at appropriate dosages) or drug responsiveness (complete freedom from seizures for at least a year). Samples were genotyped by Applied Biosystems Genotyping Assays with TaqMan probes. Association was evaluated by stratified bivariate analysis using contingency tables. A significant association was found between ABCB1_3435C>T polymorphism and pharmacoresistance in symptomatic epilepsies (n=69, p=0.008), but not in idiopathic (n=97) or in cryptogenic (n= 123) ones. Patients with ABCB1_3435TT genotype had a lower risk of pharmacoresistance than those with ABCB1_CC genotype in symptomatic epilepsies (OR: 0.20, 95%CI: 0.07-0.58). In contrast, the risk was higher in idiopathic epilepsies (OR: 11.0, 95%CI: 1.1-106.8). The interaction between the etiology and the polymorphism was significant (p=0.002). Pharmacoresistance risk in patients with ABCB1_2677TT genotype was also lower than in those with ABCB1_2677CC genotype in symptomatic epilepsies and higher in idiopathic epilepsies but ORs were not significant. ABCB1_3435TT genotype is associated with a lower risk of pharmacoresistance than ABCB1_3435CC genotype in patients with symptomatic epilepsies, but not in idiopathic or cryptogenic epilepsies.Peer Reviewe