Enfermedad cardiovascular previa y posterior a la infección por COVID-19. Supervivencia a un año / Cardiovascular disease before and after COVID-19 infection: One-year survival

Objetivos Analizar el riesgo de COVID-19 con relación a la morbilidad previa, así como el riesgo de nuevos eventos cardiovasculares (ECV) en pacientes COVID-19 y la supervivencia a un año. Metodología Estudio casos-control y estudio de cohortes prospectivo. Se incluyeron 275 pacientes aleatorizados >18 años diagnosticados de COVID-19 y se aparearon con 825 COVID-19 negativos por edad y sexo (proporción 1:3). Las variables principales fueron diagnóstico de COVID-19 y eventos post-COVID-19. Se estudiaron variables sociodemográficas, comorbilidad y ECV previo. Se realizaron sendos modelos predictivos de factores asociados al desarrollo de COVID-19 y de ECV post-COVID-19, así como un análisis de supervivencia a un año. Resultados Los varones con ECV previo duplican el riesgo de padecer COVID-19 (odds ratio [OR] 2,11; intervalo de confianza [IC] 95% 1,32–3,36). En las mujeres el riesgo aumenta con la edad (OR 1,01; IC 95% 1,00–1,02), la diabetes mellitus (DM) (OR 1,90; IC 95% 1,14–3,17) y el deterioro cognitivo (OR 4,88; IC 95% 2,50–9,53). La inmunosupresión actúa como factor protector en ambos sexos. La edad (OR 1,02; IC 95% 1,00–1,04), hipertensión arterial (HTA) (OR 2,21; IC 95% 1,17–4,17), la infección COVID-19 (OR 4,81; IC 95% 2,89–7,98) y el ECV previo (OR 4,46; IC 95% 2,56–7,75) predicen el desarrollo de un nuevo ECV post-COVID-19. Los pacientes COVID-19 positivos tienen menor supervivencia (mediana de siete vs. 184 días). Conclusiones El ECV previo en varones y la DM junto al deterioro cognitivo en mujeres aumentan el riesgo de presentar COVID-19. La edad, HTA, ECV previo y la infección COVID-19 predicen la aparición de un ECV (AU)

Aim To analyze the risk of COVID-19 in relation to previous morbidity; to analyze the risk of new cardiovascular events (CVE) in COVID-19 patients and one-year survival. Methodology Case–control study and prospective cohort study. Two hundred and seventy-five randomized patients >18 years old with COVID-19 were included and matched with 825 without COVID-19 by age and sex (ratio 1:3). The main variables were diagnosis of COVID-19 and post-COVID-19 events. Sociodemographic variables, comorbidity, and previous CVD were studied. Two predictive models of factors associated with the development of COVID-19 and post-COVID-19 CVE were performed, as well as a one-year survival analysis. Results Men with a previous CVE double the risk of suffering from COVID-19 (OR 2.11; 95% CI: 1.32–3.36). In women, the risk increases with age (OR 1.01; 95% CI: 1.00–1.02), diabetes (DM) (OR 1.90; 95% CI: 1.14–3.17) and cognitive impairment (OR 4.88; 95% CI: 2.50–9.53). Immunosuppression acts as a protective factor in both sexes. Age (OR 1.02; 95% CI: 1.00–1.04), arterial hypertension (OR 2.21; 95% CI: 1.17–4.17), COVID-19 infection (OR 4.81; 95% CI: 2.89–7.98) and previous CVE (OR 4.46; 95% CI: 2.56–7.75) predict the development of a new post-COVID-19 CVE. Positive COVID-19 has lower survival (median 7 days vs. 184 days). Conclusions Previous CVE in men and DM along with cognitive impairment in women increase the risk of presenting COVID-19. Age, arterial hypertension, previous CVE, and COVID-19 infection predict the appearance of new CVE (AU)

[Cardiovascular disease before and after COVID-19 infection: One-year survival]. / Enfermedad cardiovascular previa y posterior a la infección por COVID-19. Supervivencia a un año.

AIM: To analyze the risk of COVID-19 in relation to previous morbidity; to analyze the risk of new cardiovascular events (CVE) in COVID-19 patients and one-year survival. METHODOLOGY: Case-control study and prospective cohort study. Two hundred and seventy-five randomized patients >18 years old with COVID-19 were included and matched with 825 without COVID-19 by age and sex (ratio 1:3). The main variables were diagnosis of COVID-19 and post-COVID-19 events. Sociodemographic variables, comorbidity, and previous CVD were studied. Two predictive models of factors associated with the development of COVID-19 and post-COVID-19 CVE were performed, as well as a one-year survival analysis. RESULTS: Men with a previous CVE double the risk of suffering from COVID-19 (OR 2.11; 95% CI: 1.32-3.36). In women, the risk increases with age (OR 1.01; 95% CI: 1.00-1.02), diabetes (DM) (OR 1.90; 95% CI: 1.14-3.17) and cognitive impairment (OR 4.88; 95% CI: 2.50-9.53). Immunosuppression acts as a protective factor in both sexes. Age (OR 1.02; 95% CI: 1.00-1.04), arterial hypertension (OR 2.21; 95% CI: 1.17-4.17), COVID-19 infection (OR 4.81; 95% CI: 2.89-7.98) and previous CVE (OR 4.46; 95% CI: 2.56-7.75) predict the development of a new post-COVID-19 CVE. Positive COVID-19 has lower survival (median 7 days vs. 184 days). CONCLUSIONS: Previous CVE in men and DM along with cognitive impairment in women increase the risk of presenting COVID-19. Age, arterial hypertension, previous CVE, and COVID-19 infection predict the appearance of new CVE.

Variabilidad y tendencias en el consumo de fármacos para los trastornos por déficit de atención e hiperactividad en Castilla-La Mancha, España (1992-2015) / Variability and trends in the consumption of drugs for treating attention-deficit/hyperactivity disorder in Castile-La Mancha, Spain (1992-2015)

INTRODUCCIÓN: El trastorno por déficit de atención e hiperactividad (TDAH) es uno de los trastornos conductuales más frecuentes de la infancia, se estima su prevalencia en España en un 5-9%. Existen varios fármacos para esta patología como el metilfenidato, la atomoxetina y la lisdexanfetamina cuyos consumos están creciendo anualmente. MATERIAL Y MÉTODOS: Se estima la prevalencia de TDAH a través del cálculo de las dosis diarias definidas por 1.000 habitantes y día de cada fármaco y el total (grupo terapéutico N06BA), durante los años 1992-2015, para cada una de las provincias de Castilla-La Mancha (España). Se observa la tendencia, sus puntos de cambio y los porcentajes anuales de cambio mediante modelos de regresión de joinpoint. RESULTADOS: Se estima una prevalencia mínima de TDAH de 13,22 casos por 1.000 habitantes y día para Castilla-La Mancha en la población de 5 a 19 años, existiendo una variabilidad provincial (p < 0,05). En su conjunto, el consumo se ha incrementado un porcentaje anual de cambio de 10,3% desde 1992 a 2015 con varios años o puntos de inflexión (2000, 2009 y 2012). El metilfenidato supone el 89,6% de los fármacos consumidos, seguido por la lisdexanfetamina con un 8%. CONCLUSIONES: El consumo de fármacos permite estimar la distribución de TDAH en Castilla-La Mancha. Se observa un crecimiento en el consumo de estos fármacos, y se observa una variabilidad provincial en su consumo, lo que supone diferencias en la práctica médica frente a esta enfermedad

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioural disorders of childhood; its prevalence in Spain is estimated at 5-9%. Available treatments for this condition include methylphenidate, atomoxetine, and lisdexamfetamine, whose consumption increases each year. MATERIAL AND METHODS: The prevalence of ADHD was estimated by calculating the defined daily dose per 1,000 population per day of each drug and the total doses (therapeutic group N06BA) between 1992 and 2015 in each of the provinces of Castile-La Mancha (Spain). Trends, joinpoints, and annual percentages of change were analysed using joinpoint regression models. RESULTS: The minimum prevalence of ADHD in the population of Castile-La Mancha aged 5 to 19 was estimated at 13.22 cases per 1,000 population per day; prevalence varied across provinces (p<.05). Overall consumption has increased from 1992 to 2015, with an annual percentages of change of 10.3% and several joinpoints (2000, 2009, and 2012). methylphenidate represents 89.6% of total drug consumption, followed by lisdexamfetamine at 8%. CONCLUSIONS: Analysing drug consumption enables us to estimate the distribution of ADHD patients in Castile-La Mancha. Our data show an increase in the consumption of these drugs as well as differences in drug consumption between provinces, which reflect differences in ADHD management in clinical practice

Variability and trends in the consumption of drugs for treating attention-deficit/hyperactivity disorder in Castile-La Mancha, Spain (1992-2015). / Variabilidad y tendencias en el consumo de fármacos para los trastornos por déficit de atención e hiperactividad en Castilla-La Mancha, España (1992-2015).

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioural disorders of childhood; its prevalence in Spain is estimated at 5-9%. Available treatments for this condition include methylphenidate, atomoxetine, and lisdexamfetamine, whose consumption increases each year. MATERIAL AND METHODS: The prevalence of ADHD was estimated by calculating the defined daily dose per 1,000 population per day of each drug and the total doses (therapeutic group N06BA) between 1992 and 2015 in each of the provinces of Castile-La Mancha (Spain). Trends, joinpoints, and annual percentages of change were analysed using joinpoint regression models. RESULTS: The minimum prevalence of ADHD in the population of Castile-La Mancha aged 5 to 19 was estimated at 13.22 cases per 1,000 population per day; prevalence varied across provinces (p<.05). Overall consumption has increased from 1992 to 2015, with an annual percentages of change of 10.3% and several joinpoints (2000, 2009, and 2012). methylphenidate represents 89.6% of total drug consumption, followed by lisdexamfetamine at 8%. CONCLUSIONS: Analysing drug consumption enables us to estimate the distribution of ADHD patients in Castile-La Mancha. Our data show an increase in the consumption of these drugs as well as differences in drug consumption between provinces, which reflect differences in ADHD management in clinical practice.

Anatomical pathways for auditory memory II: information from rostral superior temporal gyrus to dorsolateral temporal pole and medial temporal cortex.

Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 min. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40 s. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys' auditory memory performance. The anatomical pathways for auditory memory may differ from those in vision. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC). We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG), and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY) and anterograde (10% BDA 10,000 mW) tracer injections in rSTG and the dorsolateral area 38 DL of the temporal pole. Results showed that area 38DL receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38DL projects densely to area 35 of PRC, entorhinal cortex (EC), and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys.

The human parahippocampal region: I. Temporal pole cytoarchitectonic and MRI correlation.

The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species.

Subicular and CA1 hippocampal projections to the accessory olfactory bulb.

The hippocampal formation is anatomically and functionally related to the olfactory structures especially in rodents. The entorhinal cortex (EC) receives afferent projections from the main olfactory bulb; this constitutes an olfactory pathway to the hippocampus. In addition to the olfactory system, most mammals possess an accessory olfactory (or vomeronasal) system. The relationships between the hippocampal formation and the vomeronasal system are virtually unexplored. Recently, a centrifugal projection from CA1 to the accessory olfactory bulb has been identified using anterograde tracers. In the study reported herein, experiments using anterograde tracers confirm this projection, and injections of retrograde tracers show the distribution and morphology of a population of CA1 and ventral subicular neurons projecting to the accessory olfactory bulb of rats. These results extend previous descriptions of hippocampal projections to the accessory olfactory bulb by including the ventral subiculum and characterizing the morphology, neurochemistry (double labeling with somatostatin), and distribution of such neurons. These data suggest feedback hippocampal control of chemosensory stimuli in the accessory olfactory bulb. Whether this projection processes spatial information on conspecifics or is involved in learning and memory processes associated with chemical stimuli remains to be elucidated.

Vomeronasal inputs to the rodent ventral striatum.

Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.

Convergence of unimodal and polymodal sensory input to the entorhinal cortex in the fascicularis monkey.

The hippocampal formation is a key structure in memory formation and consolidation. The hippocampus receives information from different cortical and subcortical sources. Cortical information is mostly funneled to the hippocampus through the entorhinal cortex (EC) in a bi-directional way that ultimately ends in the cortex. Retrograde tracing studies in the nonhuman primate indicate that more than two-thirds of the cortical afferents to the EC come from polymodal sensory association areas. Although some evidence for the projection from visual unimodal cortex to the EC exists, inputs from other visual and auditory unimodal association areas, and the possibility of their convergence with polymodal input in the EC remains largely undisclosed. We studied 10 Macaca fascicularis monkeys in which cortical deposits of the anterograde tracer biotinylated dextran-amine were made into different portions of visual and auditory unimodal association cortices in the temporal lobe, and in polymodal association cortex at the upper bank of the superior temporal sulcus. Visual and auditory unimodal as well as polymodal cortical areas projected to the EC. Both visual unimodal and polymodal association cortices presented dense projections, while those from unimodal auditory association cortex were more patchy and less dense. In all instances, the projection distributed in both the superficial and deep layers of the EC. However, while polymodal cortex projected to all layers (including layer I), visual unimodal cortex did not project to layer I, and auditory unimodal cortex projected less densely, scattered through all layers. Topographically, convergence from the three cortical areas studied can be observed in the lateral rostral and lateral caudal subfields. The present study suggests that unimodal and polymodal association cortical inputs converge in the lateral EC, thereby providing the possibility for the integration of complex stimuli for internal representations in declarative memory elaboration.

Topographical and laminar distribution of cortical input to the monkey entorhinal cortex.

Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either (3)H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I-III) while others were heavier to deep layers (V-VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.

Reciprocal connections between olfactory structures and the cortex of the rostral superior temporal sulcus in the Macaca fascicularis monkey.

Convergence of sensory modalities in the nonhuman primate cerebral cortex is still poorly understood. We present an anatomical tracing study in which polysensory association cortex located at the fundus and upper bank of the rostral superior temporal sulcus presents reciprocal connections with primary olfactory structures. At the same time, projections from this polysensory area reach multiple primary olfactory centres. Retrograde (Fast Blue) and anterograde (biotinylated dextran-amine and 3H-amino acids) tracers were injected into primary olfactory structures and rostral superior temporal sulcus. Retrograde tracers restricted to the anterior olfactory nucleus resulted in labelled neurons in the rostral portion of the upper bank and fundus of superior temporal sulcus. Injections of biotinylated dextran-amine at the fundus and upper bank of the superior temporal sulcus confirmed this projection by labelling axons in the dorsal and lateral portions of the anterior olfactory nucleus, as well as piriform, periamygdaloid and entorhinal cortices. Retrograde tracer injections at the rostral superior temporal sulcus resulted in neuronal labelling in the anterior olfactory nucleus, piriform, periamygdaloid and entorhinal cortices, thus providing confirmation of the reciprocity between primary olfactory structures and the cortex at the rostral superior temporal sulcus. The reciprocal connections between the rostral part of superior temporal sulcus and primary olfactory structures represent a convergence for olfactory and other sensory modalities at the cortex of the rostral temporal lobe.

Postnatal development of calcium-binding proteins immunoreactivity (parvalbumin, calbindin, calretinin) in the human entorhinal cortex.

The entorhinal cortex is an essential component in the organization of the human hippocampal formation related to cortical activity. It transfers, neocortical information (ultimately distributed to the dentate gyrus and hippocampus) and receives most of the hippocampal output directed to neocortex. At birth, the human entorhinal cortex presents similar layer organization as in adults, although layer II (cell islands) and upper layer III have a protracted maturation. The presence of interneurons expressing calcium-binding proteins (parvalbumin, calbindin-D28K (calbindin) and calretinin) is well documented in the adult human entorhinal cortex. In many of them the calcium binding is co-localized with GABA. Parvalbumin-immunoreactive cells and fibers were virtually absent at birth, their presence increasing gradually in deep layer III, mostly in the lateral and caudal portions of the entorhinal cortex from the 5th month onwards. Calbindin immunoreactive cells and fibers were present at birth, mainly in layers II and upper III; mostly at rostral and lateral portions of the entorhinal cortex, increasing in number and extending to deep layers from the 5th month onwards. Calretinin immunoreactivity was present at birth, homogeneously distributed over layers I, II and upper V, throughout the entorhinal cortex. A substantial increase in the number of calretinin neurons in layer V was observed at the 5th month. The postnatal development of parvalbumin, calbindin and calretinin may have an important role in the functional maturation of the entorhinal cortex through the control of hippocampal, cortical and subcortical information.