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Cortical pathology involving inflammatory and neurodegenerative mechanisms is a hallmark of multiple sclerosis and a correlate of disease progression and cognitive decline. Astrocytes play a pivotal role in multiple sclerosis initiation and progression but astrocyte-neuronal network alterations contributing to gray matter pathology remain undefined. Here we unveil deregulation of astrocytic calcium signaling and astrocyte-to-neuron communication as key pathophysiological mechanisms of cortical dysfunction in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using two-photon imaging ex vivo and fiber photometry in freely behaving mice, we found that acute EAE was associated with the emergence of spontaneously hyperactive cortical astrocytes exhibiting dysfunctional responses to cannabinoid, glutamate and purinoreceptor agonists. Abnormal astrocyte signaling by Gi and Gq protein coupled receptors was observed in the inflamed cortex. This was mirrored by treatments with pro-inflammatory factors both in vitro and ex vivo, suggesting cell-autonomous effects of the cortical neuroinflammatory environment. Finally, deregulated astrocyte calcium activity was associated with an enhancement of glutamatergic gliotransmission and a shift of astrocyte-mediated short-term and long-term plasticity mechanisms towards synaptic potentiation. Overall, our data identify astrocyte-neuronal network dysfunctions as key pathological features of gray matter inflammation in multiple sclerosis and potentially additional neuroimmunological disorders.

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OBJETIVO: Evaluar el control glucémico de pacientes de edad avanzada, con diabetes mellitus tipo 2 (DM2), en tratamiento con varios antidiabéticos, y analizar el efecto de una intervención. MATERIAL Y MÉTODOS: Estudio descriptivo transversal y observacional de prevalencia que incluyó a pacientes ≥75 años con DM2, en tratamiento con 2 o más hipoglucemiantes. Se analizó la adecuación de los tratamientos siguiendo las recomendaciones actuales para este grupo poblacional, la prevalencia de complicaciones macro y microvasculares, demencia e hipoglucemias, los tratamientos empleados y la adherencia. Se realizó una intervención para optimizar la prescripción. RESULTADOS: Se incluyeron 215 pacientes. El 54,4% fueron mujeres, con edad media de 82,0±4,1 años, el 77,2% tenía complicaciones macro y/o microvasculares y el 7,4% demencia. En el 67,9% se detectó inadecuación por control glucémico demasiado intensivo (55,6% HbA1c<7,5%) o no estar ajustada la posología a su filtrado glomerular (51,0%). El 81,4% estaba en tratamiento con fármacos con riesgo de producir hipoglucemias; el 2,3% tenía algún episodio registrado. La HbA1c media fue mayor en los no adherentes (8,1±1,6% vs. 7,5±1,3%, p < 0,05). Tras la intervención disminuyó la intensidad del tratamiento hipoglucemiante en el 36,2% de los pacientes, y se adecuó la posología en el 23,1% de los fármacos que precisaban ajuste. El porcentaje de sobretratamiento se redujo al 40,0% (p < 0,01). CONCLUSIONES: Más de la mitad de los pacientes mayores, con DM2 e importantes comorbilidades, tenía un control glucémico demasiado estricto. La puesta en marcha de un programa de intervención ha permitido mejorar la seguridad y la adecuación de los tratamientos

OBJECTIVE: To evaluate blood-glucose control in elderly patients with type 2 diabetes mellitus (T2DM), who are receiving various anti-diabetic treatments, and to analyse the effect of an intervention. MATERIAL AND METHODS: Cross-sectional, descriptive, and observational study of prevalence that included patients who were ≥75 years old with T2DM and being treated with two or more antidiabetic drugs. The adequacy of treatments following current recommendations for this population group was analysed, together with the prevalence of macro- and micro-vascular complications, dementia, and hypoglycaemia, the treatments used, and adherence. An intervention was carried out to optimise prescription. RESULTS: A total of 215 patients were included, of which 54.4% were women. The mean age was 82.0±4.1, and 77.2% had micro- and/or macrovascular complications, and 7.4% had dementia. Inadequacy was detected in 67.9% due to an overly intensive blood glucose control (55.6% HbA1c<7.5%), or that the dosage was not adapted to glomerular filtration (51.0%). The large majority (81.4%) were being treated with drugs with a risk of producing hypoglycaemia (2.3% had recorded episodes). The HbA1c mean was higher in non-adherent patients (8.1±1.6% vs 7.5±1.3%, P<.05). After the intervention, the intensity of hypoglycaemic treatment was reduced in 36.2% of patients, and the dosage of drugs that required adjustment was corrected in 23.1%. The percentage of overtreatment decreased to 40.0% (P<.01). CONCLUSIONS: More than half of the elderly patients with T2DM and important comorbidities had an overly strict glycaemic control. The launch of an intervention programme has allowed for an improvement in safety and for the optimisation of treatments

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OBJECTIVE: To evaluate blood-glucose control in elderly patients with type 2 diabetes mellitus (T2DM), who are receiving various anti-diabetic treatments, and to analyse the effect of an intervention. MATERIAL AND METHODS: Cross-sectional, descriptive, and observational study of prevalence that included patients who were ≥75 years old with T2DM and being treated with two or more antidiabetic drugs. The adequacy of treatments following current recommendations for this population group was analysed, together with the prevalence of macro- and micro-vascular complications, dementia, and hypoglycaemia, the treatments used, and adherence. An intervention was carried out to optimise prescription. RESULTS: A total of 215 patients were included, of which 54.4% were women. The mean age was 82.0±4.1, and 77.2% had micro- and/or macrovascular complications, and 7.4% had dementia. Inadequacy was detected in 67.9% due to an overly intensive blood glucose control (55.6% HbA1c<7.5%), or that the dosage was not adapted to glomerular filtration (51.0%). The large majority (81.4%) were being treated with drugs with a risk of producing hypoglycaemia (2.3% had recorded episodes). The HbA1c mean was higher in non-adherent patients (8.1±1.6% vs 7.5±1.3%, P<.05). After the intervention, the intensity of hypoglycaemic treatment was reduced in 36.2% of patients, and the dosage of drugs that required adjustment was corrected in 23.1%. The percentage of overtreatment decreased to 40.0% (P<.01). CONCLUSIONS: More than half of the elderly patients with T2DM and important comorbidities had an overly strict glycaemic control. The launch of an intervention programme has allowed for an improvement in safety and for the optimisation of treatments.

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En general la orina hematúrica tiene un aspecto rojizo, morado, amarronado, negruzco o incluso verde claro. Esta hematuria macroscópica es fácil de reconocer y, para constatarla, lo más sencillo es hacer orinar al paciente en un vaso, ya que un mililitro de sangre en un litro de orina es suficiente para objetivarla. Las hematurias microscópicas pueden aparecer en orinas de aspecto claro u opalino, incluso transparente. Siempre debe estudiarse una hematuria ya que su importancia no depende de su intensidad, sino de la causa que la motiva (AU)

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El hallazgo de una o varias adenopatías es un hecho frecuente en la práctica clínica diaria. En ocasiones es el propio paciente el que nos consulta por se él quien las descubre y otras veces las encontramos al realizar una exploración. Su abordaje adecuado es necesario para un mejor manejo de esta patología tan habitual (AU)

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