Psychiatric polygenic risk as a predictor of COVID-19 risk and severity: insight into the genetic overlap between schizophrenia and COVID-19.

Despite the high contagion and mortality rates that have accompanied the coronavirus disease-19 (COVID-19) pandemic, the clinical presentation of the syndrome varies greatly from one individual to another. Potential host factors that accompany greater risk from COVID-19 have been sought and schizophrenia (SCZ) patients seem to present more severe COVID-19 than control counterparts, with certain gene expression similarities between psychiatric and COVID-19 patients reported. We used summary statistics from the last SCZ, bipolar disorder (BD), and depression (DEP) meta-analyses available on the Psychiatric Genomics Consortium webpage to calculate polygenic risk scores (PRSs) for a target sample of 11,977 COVID-19 cases and 5943 subjects with unknown COVID-19 status. Linkage disequilibrium score (LDSC) regression analysis was performed when positive associations were obtained from the PRS analysis. The SCZ PRS was a significant predictor in the case/control, symptomatic/asymptomatic, and hospitalization/no hospitalization analyses in the total and female samples; and of symptomatic/asymptomatic status in men. No significant associations were found for the BD or DEP PRS or in the LDSC regression analysis. SNP-based genetic risk for SCZ, but not for BD or DEP, may be associated with higher risk of SARS-CoV-2 infection and COVID-19 severity, especially among women; however, predictive accuracy barely exceeded chance level. We believe that the inclusion of sexual loci and rare variations in the analysis of genomic overlap between SCZ and COVID-19 will help to elucidate the genetic commonalities between these conditions.

¿Existe mayor riesgo de suicidio en pacientes diagnosticados de una enfermedad neurológica? / Do patients diagnosed with a neurological disease present increased risk of suicide?

Introducción: Las enfermedades neurológicas representan la principal causa de discapacidad y la segunda causa de muerte a nivel mundial. El dolor físico y psicológico, la desesperanza y la desconexión con el medio están presentes tras el diagnóstico de numerosos procesos neurológicos y especialmente de las enfermedades neurodegenerativas.DesarrolloExiste un mayor riesgo de suicidio en pacientes con enfermedades neurológicas comunes como la epilepsia, la migraña y la esclerosis múltiple, así como en quienes padecen trastornos degenerativos como la enfermedad de Alzheimer, la enfermedad de Huntington, la esclerosis lateral amiotrófica o la enfermedad de Parkinson. En la mayoría de los casos, la ideación suicida aparece en la etapa próxima al diagnóstico, ante sintomatología invalidante, y/o en pacientes que presentan comorbilidad psiquiátrica (a menudo asociada con dichas dolencias neurológicas).ConclusionesPara una prevención efectiva del suicidio en este grupo de la población debe evaluarse el riesgo principalmente en pacientes recién diagnosticados, ante la expresión de marcada desesperanza, ante sintomatología invalidante y en pacientes que presentan comorbilidad psiquiátrica (especialmente síntomas depresivos). La formación de los especialistas para detectar signos de alerta es fundamental tanto para que puedan hacer un correcto abordaje como para que sean capaces de determinar cuándo es necesaria la valoración de un especialista en psiquiatría. (AU)

Introduction: Neurological diseases are the leading cause of disability and the second leading cause of death worldwide. Physical and psychological pain, despair, and disconnection with the environment are observed after the diagnosis of numerous neurological processes, particularly neurodegenerative diseases.DevelopmentA higher risk of suicide is observed in patients with such common neurological diseases as epilepsy, migraine, and multiple sclerosis, as well as in those with such degenerative disorders as Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, and Parkinson's disease. In most cases, suicidal ideation appears in the early stages after diagnosis, in the presence of disabling symptoms, and/or in patients with psychiatric comorbidities (often associated with these neurological diseases).ConclusionsEffective suicide prevention in this population group requires assessment of the risk of suicide mainly in newly diagnosed patients, in patients showing unmistakable despair or disabling symptoms, and in patients presenting psychiatric comorbidities (especially depressive symptoms). It is essential to train specialists to detect warning signs in order that they may adopt a suitable approach and determine when psychiatric assessment is required. (AU)

Do patients diagnosed with a neurological disease present increased risk of suicide?

INTRODUCTION: Neurological diseases are the leading cause of disability and the second leading cause of death worldwide. Physical and psychological pain, despair, and disconnection with the environment are observed after the diagnosis of numerous neurological processes, particularly neurodegenerative diseases. DEVELOPMENT: A higher risk of suicide is observed in patients with such common neurological diseases as epilepsy, migraine, and multiple sclerosis, as well as in those with such degenerative disorders as Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, and Parkinson's disease. In most cases, suicidal ideation appears in the early stages after diagnosis, in the presence of disabling symptoms, and/or in patients with psychiatric comorbidities (often associated with these neurological diseases). CONCLUSIONS: Effective suicide prevention in this population group requires assessment of the risk of suicide mainly in newly diagnosed patients, in patients showing unmistakable despair or disabling symptoms, and in patients presenting psychiatric comorbidities (especially depressive symptoms). It is essential to train specialists to detect warning signs in order that they may adopt a suitable approach and determine when psychiatric assessment is required.

Gravedad de COVID-19 atribuible a obesidad según IMC y CUN-BAE / Severity of COVID-19 attributable to obesity according to BMI and CUN-BAE

Introducción La obesidad es considerada un factor de riesgo en casos graves de la COVID-19, habiendo sido analizada mediante el índice de masa corporal (IMC), estimador que no correlaciona adecuadamente con el porcentaje de grasa corporal (GC). El objetivo de este estudio ha sido analizar la fracción atribuible poblacional a la GC en formas graves de COVID-19 atendiendo al IMC y al CUN-BAE. Material y métodos Estudio multicéntrico observacional de prevalencia. Se recogió información sociodemográfica, antecedentes personales, IMC y CUN-BAE, de casos positivos SARS-CoV-2, de las provincias de León y La Rioja. Mediante modelos de regresión logística se calcularon odds ratio con sus respectivos intervalos de confianza del 95% ajustando por edad y antecedentes personales, así como la fracción atribuible poblacional a la GC. Resultados Participaron 785 pacientes, 123 (15,7%) fueron graves. Se detectaron como factores de riesgo la edad, la obesidad (tanto por IMC como por CUN-BAE) y los antecedentes personales. Un 51,6% de casos graves podrían ser atribuidos a un exceso de IMC y un 61,4% a exceso de GC estimada según CUN-BAE, observándose una mayor infraestimación del riesgo en mujeres. Conclusiones El exceso de GC es un factor de riesgo para formas graves de la COVID-19 junto con la edad avanzada y la presencia de enfermedades cardiovasculares, respiratorias crónicas u oncohematológicas. El IMC infraestima el riesgo, especialmente en mujeres, siendo el CUN-BAE el predictor seleccionado por su mejor estimación del porcentaje de GC (AU)

Introduction Obesity is considered a risk factor in severe cases of COVID-19, which has been analysed using body mass index (BMI), an estimator that does not correlate adequately with body fat (BF) percentage. The aim of this study was to analyse the population attributable fraction to BF in severe forms of COVID-19 based on BMI and CUN-BAE. Material and methods Multicentre observational prevalence study. Sociodemographic information, personal history, BMI and CUN-BAE were collected in SARS-CoV-2 positive cases from the provinces of León and La Rioja. Logistic regression models were used to calculate odds ratios with their respective 95% confidence intervals adjusting for age and personal history, as well as the population attributable fraction to BF. Results Seven hundred eighty-five patients participated, 123 (15.7%) were severe. Age, obesity (both by BMI and CUN-BAE) and personal history were detected as risk factors. 51.6% of severe cases could be attributed to excess BMI and 61.4% to excess BF estimated according to CUN-BAE, with a higher underestimation of risk in women. Conclusions Excess BF is a risk factor for severe forms of COVID-19 together with advanced age and the presence of cardiovascular, chronic respiratory or oncohematological diseases. BMI underestimates the risk especially in women, being CUN-BAE the predictor selected for its better estimation of the percentage of BF (AU)

[Severity of COVID-19 attributable to obesity according to BMI and CUN-BAE]. / Gravedad de COVID-19 atribuible a obesidad según IMC y CUN-BAE.

INTRODUCTION: Obesity is considered a risk factor in severe cases of COVID-19, which has been analysed using body mass index (BMI), an estimator that does not correlate adequately with body fat (BF) percentage. The aim of this study was to analyse the population attributable fraction to BF in severe forms of COVID-19 based on BMI and CUN-BAE. MATERIAL AND METHODS: Multicentre observational prevalence study. Sociodemographic information, personal history, BMI and CUN-BAE were collected in SARS-CoV-2 positive cases from the provinces of León and La Rioja. Logistic regression models were used to calculate odds ratios with their respective 95% confidence intervals adjusting for age and personal history, as well as the population attributable fraction to BF. RESULTS: Seven hundred eighty-five patients participated, 123 (15.7%) were severe. Age, obesity (both by BMI and CUN-BAE) and personal history were detected as risk factors. 51.6% of severe cases could be attributed to excess BMI and 61.4% to excess BF estimated according to CUN-BAE, with a higher underestimation of risk in women. CONCLUSIONS: Excess BF is a risk factor for severe forms of COVID-19 together with advanced age and the presence of cardiovascular, chronic respiratory or oncohematological diseases. BMI underestimates the risk especially in women, being CUN-BAE the predictor selected for its better estimation of the percentage of BF.

Resumen ejecutivo de las guías de práctica clínica en la osteoporosis posmenopáusica, glucocorticoidea y del varón (actualización 2022). Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) / Executive summary clinical practice guideline of postmenopausal, glucocortcioid-induced and male osteoporosis (2022 update). Spanish Society for Bone and Mineral Metabolism Investigation (SEIOMM)

Esta versión actualizada de las guías de osteoporosis de la Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral (SEIOMM) incorpora la información más relevante publicada en los últimos 7años, desde las guías de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos (AU)

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated (AU)

Executive summary clinical practice guideline of postmenopausal, glucocortcioid-induced and male osteoporosis (2022 update). Spanish Society for Bone and Mineral Metabolism Investigation (SEIOMM).

This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7 years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated.

Resumen ejecutivo de las Guías de práctica clínica en la osteoporosis postmenopáusica, glucocorticoidea y del varón (actualización 2022) / Executive summary clinical practice guideline of postmenopausal, glucocorticoid-induced, and male osteoporosis (2022 update)

Esta versión actualizada de la Guía de osteoporosis de la SEIOMM (Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral) incorpora la información más relevante publicada en los últimos 7 años, desde la Guía de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos. (AU)

Guías de práctica clínica en la osteoporosis postmenopáusica, glucocorticoidea y del varón (actualización 2022). Sociedad Española de Investigación Ósea y del Metabolismo Mineral (SEIOMM) / Clinical practice guidelines in postmenopausal, glucocorticoid and male osteoporosis (update 2022). Spanish Society for Bone and Mineral Metabolism Research (SEIOMM)

Esta actualización de las Guías incorpora la información más relevante aparecida durante los 7 años trascurridos desde la publicación de la versión anterior, especialmente en cuanto a procedimientos diagnósticos y opciones terapéuticas. Entre los primeros, merece la pena destacar la incorporación del TBS y la detección de fracturas vertebrales por densitometría. Entre los tratamientos, se consideran los nuevos fármacos anabólicos, los estudios comparativos de eficacia en osteoporosis grave, las pautas de actuación tras la suspensión de los antirresortivos y otros esquemas de tratamiento secuencial y combinado. Teniendo en cuenta todo ello, se actualizan los esquemas de tratamiento recomendados. (AU)

Do patients diagnosed with a neurological disease present increased risk of suicide? / ¿Existe mayor riesgo de suicidio en pacientes diagnosticados de una enfermedad neurológica?

INTRODUCTION: Neurological diseases are the leading cause of disability and the second leading cause of death worldwide. Physical and psychological pain, despair, and disconnection with the environment are observed after the diagnosis of numerous neurological processes, particularly neurodegenerative diseases. DEVELOPMENT: A higher risk of suicide is observed in patients with such common neurological diseases as epilepsy, migraine, and multiple sclerosis, as well as in those with such degenerative disorders as Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, and Parkinson's disease. In most cases, suicidal ideation appears in the early stages after diagnosis, in the presence of disabling symptoms, and/or in patients with psychiatric comorbidities (often associated with these neurological diseases). CONCLUSIONS: Effective suicide prevention in this population group requires assessment of the risk of suicide mainly in newly diagnosed patients, in patients showing unmistakable despair or disabling symptoms, and in patients presenting psychiatric comorbidities (especially depressive symptoms). It is essential to train specialists to detect warning signs in order that they may adopt a suitable approach and determine when psychiatric assessment is required.

¿Por qué degeneran las motoneuronas? Actualización en la patogenia de la esclerosis lateral amiotrófica / Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis

Introducción: La esclerosis lateral amiotrófica (ELA) es la enfermedad degenerativa de las motoneuronas más frecuente. Aunque un pequeño porcentaje de los casos de ELA tienen un origen familiar y son secundarios a mutaciones en genes concretos, a la gran mayoría de ellos se les presupone un origen multifactorial, sin que su patogenia haya sido completamente aclarada. No obstante, en los últimos años varios estudios han aumentado el conocimiento sobre la patogenia de la enfermedad, planteando la cuestión de si se trata de una proteinopatía, una ribonucleinopatía, una axonopatía o una enfermedad del microambiente neuronal. Desarrollo: En el presente artículo revisamos los trabajos publicados tanto en pacientes como en modelos animales de ELA y discutimos la implicación de los principales procesos celulares que parecen contribuir a su patogenia (procesamiento génico, metabolismo de proteínas, estrés oxidativo, transporte axonal y relación con el microambiente neuronal). Conclusiones: Aunque la patogenia de la ELA dista de estar aclarada, los estudios recientes apuntan a la idea de que hay unos desencadenantes iniciales que varían de unos sujetos a otros, y unas vías finales de degeneración de las motoneuronas que están implicadas en la mayor parte de los casos de enfermedad

Introduction: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. Development: This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. Conclusions: ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established

Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis. / ¿Por qué degeneran las motoneuronas? Actualización en la patogenia de la esclerosis lateral amiotrófica.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. DEVELOPMENT: This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. CONCLUSIONS: ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established.

Abnormal bone turnover in individuals with low serum alkaline phosphatase.

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4 ± 13.7 versus 48.9 ± 24.4 ng/ml; p = 0.0002) and ß-crosslaps (0.21 ± 0.17 versus 0.34 ± 0.22 ng/ml, p = 0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects.

Diverging results of areal and volumetric bone mineral density in Down syndrome.

Population with Down syndrome (DS) has lower areal BMD, in association with their smaller skeletal size. However, volumetric BMD and other indices of bone microarchitecture, such as trabecular bone score (TBS) and calcaneal ultrasound (QUS), were normal. INTRODUCTION: Patients with DS have a number of risk factors that could predispose them to osteoporosis. Several studies reported that people with DS also have lower areal bone mineral density, but differences in the skeletal size could bias the analysis. METHODS: Seventy-five patients with DS and 76 controls without intellectual disability were recruited. Controls were matched for age and sex. Bone mineral density (BMD) was measure by Dual-energy X-ray Absorptiometry (DXA), and volumetric bone mineral density (vBMD) was calculated by published formulas. Body composition was also measured by DXA. Microarchitecture was measured by TBS and QUS. Serum 25-hidroxyvitamin D (25OHD), parathyroid hormone (PTH), aminoterminal propeptide of type collagen (P1NP), and C-terminal telopeptide of type I collagen (CTX) were also determined. Physical activity was assessed by the International Physical Activity Questionnaires (IPAQ-short form). To evaluate nutritional intake, we recorded three consecutive days of food. RESULTS: DS individuals had lower height (151 ± 11 vs. 169 ± 9 cm). BMD was higher in the controls (lumbar spine (LS) 0.903 ± 0.124 g/cm2 in patients and 0.997 ± 0.115 g/cm2 in the controls; femoral neck (FN) 0.761 ± .126 g/cm2 and 0.838 ± 0.115 g/cm2, respectively). vBMD was similar in the DS group (LS 0.244 ± 0.124 g/cm3; FN 0.325 ± .0.073 g/cm3) and the controls (LS 0.255 ± 0.033 g/cm3; FN 0.309 ± 0.043 g/cm3). Microarchitecture measured by QUS was slightly better in DS, and TBS measures were similar in both groups. 25OHD, PTH, and CTX were similar in both groups. P1NP was higher in the DS group. Time spent on exercise was similar in both groups, but intensity was higher in the control group. Population with DS has correct nutrition. CONCLUSIONS: Areal BMD is reduced in DS, but it seems to be related to the smaller body and skeletal size. In fact, the estimated volumetric BMD is similar in patients with DS and in control individuals. Furthermore, people with DS have normal bone microarchitecture.

Diplejía facial y afagia de aparición súbita / Sudden onset of facial diplegia and aphagia

No disponible

Analysis of post-transplant chimerism by using a single amplification reaction of 38 Indel polymorphic loci.

In order to detect chimerism after allogeneic hematopoietic SCT (HSCT), several methods have been developed. In this study we describe the use of a set of insertion/deletion (Indel) polymorphic loci to determine the level of donor cell engraftment. We analyzed 50 DNA samples from patients who had undergone HSCT, and also several artificial chimeric samples created by mixing different DNA specimens from non-transplanted donors in various proportions. A specific set of 38 autosomic Indel polymorphisms were analyzed. For comparison purposes, a set of 15 short tandem repeats (STRs) were analyzed using the Identifiler Plus Amplification Kit. Our results suggest that Indel-based and STR-based procedures behave similarly in most cases. However, Indel analysis may provide additional information in some cases with a small minor chimeric component or when the presence of stutter bands complicates chimerism estimation.

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells.

NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

Anti-TNF-α therapy in the management of severe neurosarcoidosis: a report of five cases from a single centre and literature review.

Neurologic manifestations are found in 5-15 % of patients with sarcoidosis. This granulomatous disease may affect any part of the peripheral or the central nervous system, being potentially severe and difficult to treat. Corticosteroids are the cornerstone of therapy in sarcoidosis. However, some patients become resistant or experience side effects to corticosteroids. In these patients, second line therapies including immunosuppressive drugs such as methotrexate, azathioprine, mycophenolate, cyclophosphamide and leflunomide have been used. Anti-TNF-α drugs have been proposed as a therapeutic option for those who are refractory to immunosuppressive drugs or initially in cases of severe sarcoidosis. We report on 5 patients with neurosarcoidosis treated with anti-TNF-α drugs in our center. A literature review of patients with neurosarcoidosis treated with anti-TNF-α drugs was conducted. In our series successful response to anti-TNF-α therapy was achieved. However, the high frequency of relapses following anti-TNF-α discontinuation makes necessary a close follow-up of these patients when the biologic agent is stopped.