SARS-CoV-2 Infection in Multiple Sclerosis

To understand COVID-19 characteristics in people with multiple sclerosis (MS) and identify high-risk individuals due to their immunocompromised state resulting from the use of disease-modifying treatments. Retrospective and multicenter registry in patients with MS with suspected or confirmed COVID-19 diagnosis and available disease course (mild = ambulatory; severe = hospitalization; and critical = intensive care unit/death). Cases were analyzed for associations between MS characteristics and COVID-19 course and for identifying risk factors for a fatal outcome. Of the 326 patients analyzed, 120 were cases confirmed by real-time PCR, 34 by a serologic test, and 205 were suspected. Sixty-nine patients (21.3%) developed severe infection, 10 (3%) critical, and 7 (2.1%) died. Ambulatory patients were higher in relapsing MS forms, treated with injectables and oral first-line agents, whereas more severe cases were observed in patients on pulsed immunosuppressors and critical cases among patients with no therapy. Severe and critical infections were more likely to affect older males with comorbidities, with progressive MS forms, a longer disease course, and higher disability. Fifteen of 33 patients treated with rituximab were hospitalized. Four deceased patients have progressive MS, 5 were not receiving MS therapy, and 2 were treated (natalizumab and rituximab). Multivariate analysis showed age (OR 1.09, 95% CI, 1.04-1.17) as the only independent risk factor for a fatal outcome. This study has not demonstrated the presumed critical role of MS therapy in the course of COVID-19 but evidenced that people with MS with advanced age and disease, in progressive course, and those who are more disabled have a higher probability of severe and even fatal diseas

Spread of a SARS-CoV-2 variant through Europe in the summer of 2020.

Following its emergence in late 2019, the spread of SARS-CoV-21,2 has been tracked by phylogenetic analysis of viral genome sequences in unprecedented detail3–5. Although the virus spread globally in early 2020 before borders closed, intercontinental travel has since been greatly reduced. However, travel within Europe resumed in the summer of 2020. Here we report on a SARS-CoV-2 variant, 20E (EU1), that was identified in Spain in early summer 2020 and subsequently spread across Europe. We find no evidence that this variant has increased transmissibility, but instead demonstrate how rising incidence in Spain, resumption of travel, and lack of effective screening and containment may explain the variant’s success. Despite travel restrictions, we estimate that 20E (EU1) was introduced hundreds of times to European countries by summertime travellers, which is likely to have undermined local efforts to minimize infection with SARS-CoV-2. Our results illustrate how a variant can rapidly become dominant even in the absence of a substantial transmission advantage in favourable epidemiological settings. Genomic surveillance is critical for understanding how travel can affect transmission of SARS-CoV-2, and thus for informing future containment strategies as travel resumes. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Astrocytes in neurodegenerative diseases (I): function and molecular description

Introduction: Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. Development: This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. Conclusion: Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases. Resumen: Introducción: Los astrocitos han sido considerados como células de sostén en el SNC. Sin embargo, hoy día se sabe que participan de forma activa en muchas de las funciones del SNC y que pueden tener un papel destacado en las enfermedades neurodegenerativas. Desarrollo: Se revisan las funciones del astrocito en el desarrollo y plasticidad del SNC, en el control sináptico, regulación del flujo sanguíneo, energía y metabolismo, en la barrera hematoencefálica, regulación de los ritmos circadianos, metabolismo lipídico y secreción de lipoproteínas y en la neurogénesis. Asimismo, se revisan sus marcadores y el papel de la astrogliosis. Conclusión: Los astrocitos tienen un papel activo en el SNC. Su conocimiento parece esencial para comprender los mecanismos de las enfermedades neurodegenerativas. Keywords: Astrocyte, Neurodegeneration, Glial fibrillary acidic protein, Astrocytosis, Glia, Neurodegenerative diseases, Palabras clave: Astrocito, Neurodegeneración, Proteína ácida fibrilar glial, Astrocitosis, Glía, Enfermedades neurodegenerativa

Astrocitos en las enfermedades neurodegenerativas (I): función y caracterización molecular

Resumen: Introducción: Los astrocitos han sido considerados como células de sostén en el SNC. Sin embargo, hoy día se sabe que participan de forma activa en muchas de las funciones del SNC y que pueden tener un papel destacado en las enfermedades neurodegenerativas. Desarrollo: Se revisan las funciones del astrocito en el desarrollo y plasticidad del SNC, en el control sináptico, regulación del flujo sanguíneo, energía y metabolismo, en la barrera hematoencefálica, regulación de los ritmos circadianos, metabolismo lipídico y secreción de lipoproteínas y en la neurogénesis. Asimismo, se revisan sus marcadores y el papel de la astrogliosis. Conclusión: Los astrocitos tienen un papel activo en el SNC. Su conocimiento parece esencial para comprender los mecanismos de las enfermedades neurodegenerativas. Abstract: Introduction: Astrocytes have been considered mere supporting cells in the CNS. However, we now know that astrocytes are actively involved in many of the functions of the CNS and may play an important role in neurodegenerative diseases. Development: This article reviews the roles astrocytes play in CNS development and plasticity; control of synaptic transmission; regulation of blood flow, energy, and metabolism; formation of the blood-brain barrier; regulation of the circadian rhythms, lipid metabolism and secretion of lipoproteins; and in neurogenesis. Astrocyte markers and the functions of astrogliosis are also described. Conclusion: Astrocytes play an active role in the CNS. A good knowledge of astrocytes is essential to understanding the mechanisms of neurodegenerative diseases. Palabras clave: Astrocito, Neurodegeneración, Proteína ácida fibrilar glial, Astrocitosis, Glía, Enfermedades neurodegenerativas, Keywords: Astrocyte, Neurodegeneration, Glial fibrillary acidic protein, Astrocytosis, Glia, Neurodegenerative disease

Cell therapy in amyotrophic lateral sclerosis: science and controversy

Stem cell therapy is seen as a possible alternative for the treatment of different degenerative diseases, among which includes amyotrophic lateral sclerosis (ALS). Despite there being basic research works with this therapy in ALS, the mechanism of action of the implanted cells are still unclear. It is also unclear which type of cells to use (bone marrow, fat, dental pulp, etc.), or the most ideal administration route. Furthermore, clinical trials with mesenchymal stem cells are not very conclusive, therefore it has not been convincingly established as an alternative therapy in ALS or any other neurodegenerative disease. Despite the scientific evidence, several clinical trials have been conducted in the last few years that offer stem cell treatments for neurodegenerative diseases, giving rise to what is known as “cellular tourism”. This phenomenon has set off alarms and reactions in the scientific community. The application of these therapies must be performed following the good clinical practice guidelines in research, evidence based methodology and international ethical and scientific recommendations. Resumen: La terapia con células madre se vislumbra como una posible terapia alternativa al tratamiento de diferentes patologías degenerativas, entre las cuales se encuentra la esclerosis lateral amiotrófica (ELA). En la actualidad, a pesar de que existen trabajos de investigación básica con esta terapia en la ELA, todavía quedan sin esclarecer los mecanismos de actuación de las células madre implantadas, además de no tener claro el tipo de células a utilizar (médula ósea, grasa, pulpa dentaria, etc.) y vía de administración más idónea. A su vez, existen ensayos clínicos con células madre mesenquimales con resultados poco concluyentes, por lo que no se ha podido establecer con contundencia como una terapia alternativa en ELA o cualquier otra enfermedad neurodegenerativa. A pesar de las evidencias científicas, en los últimos años han aparecido diferentes clínicas que ofrecen tratamientos con células madre para enfermedades neurodegenerativas, dando lugar a lo que se conoce como “turismo celular”. Este fenómeno ha activado alarmas y reacciones en la comunidad científica. La aplicación de estas terapias se debe realizar siguiendo las normas de buena práctica clínica en investigación, la metodología basada en la evidencia y las recomendaciones éticas y científicas internacionales Keywords: Amyotrophic lateral sclerosis, Stem cells, Neurodegenerative disease, Cell therapy, Palabras clave: Esclerosis lateral amiotrófica, Células madre, Enfermedad neurodegenerativa, Terapia celula

Terapia celular en la esclerosis lateral amiotrófica: ciencia y controversia

Resumen: La terapia con células madre se vislumbra como una posible terapia alternativa al tratamiento de diferentes patologías degenerativas, entre las cuales se encuentra la esclerosis lateral amiotrófica (ELA). En la actualidad, a pesar de que existen trabajos de investigación básica con esta terapia en la ELA, todavía quedan sin esclarecer los mecanismos de actuación de las células madre implantadas, además de no tener claro el tipo de células a utilizar (medula ósea, grasa, pulpa dentaria, etc.) y vía de administración más idónea. A su vez, existen ensayos clínicos con células madre mesenquimales con resultados poco concluyentes, por lo que no se ha podido establecer con contundencia como una terapia alternativa en ELA o cualquier otra enfermedad neurodegenerativa. A pesar de las evidencias científicas, en los últimos años han aparecido diferentes clínicas que ofrecen tratamientos con células madre para enfermedades neurodegenerativas, dando lugar a lo que se conoce como “turismo celular”. Este fenómeno ha activado alarmas y reacciones en la comunidad científica. La aplicación de estas terapias se debe realizar siguiendo las normas de buena práctica clínica en investigación, la metodología basada en la evidencia y las recomendaciones éticas y científicas internacionales. Abstract: Stem cell therapy is seen as a possible alternative for the treatment of different degenerative diseases, among which includes amyotrophic lateral sclerosis (ALS). Despite there being basic research works with this therapy in ALS, the mechanism of action of the implanted cells are still unclear. It is also unclear which type of cells to use (bone marrow, fat, dental pulp, etc.), or the most ideal administration route. Furthermore, clinical trials with mesenchymal stem cells are not very conclusive, therefore it has not been convincingly established as an alternative therapy in ALS or any other neurodegenerative disease. Despite the scientific evidence, several clinical trials have been conducted in the last few years that offer stem cell treatments for neurodegenerative diseases, giving rise to what is known as “cellular tourism”. This phenomenon has set off alarms and reactions in the scientific community. The application of these therapies must be performed following the good clinical practice guidelines in research, evidence based methodology and international ethical and scientific recommendations. Palabras clave: Esclerosis lateral amiotrófica, Células madre, Enfermedad neurodegenerativa, Terapia celular, Keywords: Amyotrophic lateral sclerosis, Stem cells, Neurodegenerative disease, Cell therap

Molecular aspects of hepatic encephalopathy

Introduction: Liver fibrosis and its end stage, cirrhosis, is an enormous worldwide health problem. Hepatic encephalopathy (HE) or portal-systemic encephalopathy continues to be a major clinical problem of long-term cirrhosis. In this review we emphasise the molecular basis of HE and the involvement of oxidative stress in the development of this disease. Background: Several studies suggest that the pathogenesis of HE could be multifactorial and have different factors implicated, such as alterations in blood brain barrier, substances such as ammonia and manganese, and disorders in the neurotransmission of dopamine, glutamate and GABA. Development: HE is a severe complication of both acute and chronic liver failure. Neuropathologically, it is characterized by astrocyte changes known as Alzheimer type II astrocytosis. In addition, astrocytes manifest altered expression of astrocyte-specific proteins, such as, glial fibrillary acidic protein, glutamine synthetase, monoamine oxidase and peripheral type benzodiazepine receptors. Conclusions: HE is a complex neuropsychiatric syndrome associated with liver failure. These alterations are products of increases in oxidative stress in brain due to neurotoxin activity. The main strategy for HE treatment is directed at ammonia reduction, which can be achieved either by decreasing its absorption/production or increasing its removal. Resumen: Introducción: La fibrosis hepática y su etapa final, la cirrosis, representan un enorme problema de salud mundial. La encefalopatía hepática (EH) o encefalopatía portosistémica es una afección clínica de la cirrosis a largo plazo. En esta revisión se destacan las bases moleculares de la EH, así como el papel del estrés oxidativo en el desarrollo de esta enfermedad. Fuentes: Diversos estudios señalan que la EH es de origen multifactorial, las alteraciones en la barrera hematoencefálica, sustancias como el amonio y el manganeso, así como alteraciones en la neurotransmisión de dopamina, glutamato y GABA, se han implicado en la patogenia de esta enfermedad. Desarrollo: La EH es una complicación severa de la insuficiencia hepática tanto aguda como crónica. Neuropatológicamente, se caracteriza por cambios astrocitarios conocidos como astrocitosis Alzheimer tipo II y por la expresión alterada de proteínas específicas de astrocito, como la proteína acídica fibrilar glial, la glutamina sintetasa, los inhibidores de la monoaminooxidasa y los receptores periféricos tipo benzodiacepina. Conclusiones: La EH es un síndrome neuropsiquiátrico complejo asociado a una falla hepática. Estas alteraciones son producto de un incremento de estrés oxidativo en el cerebro como consecuencia de la acción de neurotoxinas. La principal estrategia para el tratamiento de la EH se dirige a la reducción del amonio, ya sea por la disminución de su absorción/producción o promoviendo su eliminación. Keywords: Hepatic encephalopathy, Ammonia, Manganese, Neurotoxins, Oxidative stress, Palabras clave: Encefalopatía hepática, Amonio, Manganeso, Neurotoxinas, Estrés oxidativ

Aspectos moleculares de la encefalopatía hepática

Resumen: Introducción: La fibrosis hepática y su etapa final, la cirrosis, representan un enorme problema de salud mundial. La encefalopatía hepática (EH) o encefalopatía portosistémica es una afección clínica de la cirrosis a largo plazo. En esta revisión se destacan las bases moleculares de la EH, así como el papel del estrés oxidativo en el desarrollo de esta enfermedad. Fuentes: Diversos estudios señalan que la EH es de origen multifactorial, las alteraciones en la barrera hematoencefálica, sustancias como el amonio y el manganeso, así como alteraciones en la neurotransmisión de dopamina, glutamato y GABA, se han implicado en la patogenia de esta enfermedad. Desarrollo: La EH es una complicación severa de la insuficiencia hepática tanto aguda como crónica. Neuropatológicamente, se caracteriza por cambios astrocitarios conocidos como astrocitosis Alzheimer tipo II y por la expresión alterada de proteínas específicas de astrocito, como la proteína acídica fibrilar glial, la glutamina sintetasa, los inhibidores de la monoaminooxidasa y los receptores periféricos tipo benzodiacepina. Conclusiones: La EH es un síndrome neuropsiquiátrico complejo asociado a una falla hepática. Estas alteraciones son producto de un incremento de estrés oxidativo en el cerebro como consecuencia de la acción de neurotoxinas. La principal estrategia para el tratamiento de la EH se dirige a la reducción del amonio, ya sea por la disminución de su absorción/producción o promoviendo su eliminación. Abstract: Introduction: Liver fibrosis and its end stage, cirrhosis, is an enormous worldwide health problem. Hepatic encephalopathy (HE) or portal-systemic encephalopathy continues to be a major clinical problem of long-term cirrhosis. In this review we emphasise the molecular basis of HE and the involvement of oxidative stress in the development of this disease. Background: Several studies suggest that the pathogenesis of HE could be multifactorial and have implicated different factors, such as alterations in blood brain barrier, substances; such as ammonia and manganese, neurotransmission disorders such as dopamine, glutamate and GABA. Development: HE is a severe complication of both acute and chronic liver failure. Neuropathologically, it is characterized by astrocyte changes known as Alzheimer type II astrocytosis. In addition, astrocytes manifest altered expression of astrocyte-specific proteins, such as, glial fibrillary acidic protein, glutamine synthetase, monoamine oxidase and peripheral type benzodiazepine receptors. Conclusions: HE is a complex neuropsychiatric syndrome associated with liver failure. These alterations are products of increases in oxidative stress in brain due to neurotoxin activity. The main strategy for HE treatment is directed at ammonia reduction, which can be achieved either by decreasing its absorption/production or increasing its removal. Palabras clave: Encefalopatía hepática, Amonio, Manganeso, Neurotoxinas, Estrés oxidativo, Keywords: Hepatic encephalopathy, Ammonia, Manganese, Neurotoxins, Oxidative stres