Polymerogenic neuroserpin causes mitochondrial alterations and activates NFκB but not the UPR in a neuronal model of neurodegeneration FENIB.

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients.

El impacto de la COVID-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de Italia: análisis multicéntrico / The impact of COVID-19 outbreak on urolithiasis emergency department admissions, hospitalizations and clinical management in central Italy: a multicentric analysis

INTRODUCCIÓN Y OBJETIVOS: Nuestro objetivo fue evaluar el impacto de la enfermedad del coronavirus de 2019 (COVID-19) en los ingresos en los servicios de urgencias (SU), las hospitalizaciones y el manejo clínico de los pacientes con urolitiasis. PACIENTES Y MÉTODOS: Realizamos un análisis retrospectivo multicéntrico de las admisiones en los servicios de urgencias de tres departamentos de urología de gran volumen (uno directamente implicado en el tratamiento de los pacientes de COVID-19 y dos no implicados) en Roma (Italia) entre marzo y abril de 2020 y en el mismo período de 2019. Se realizó un análisis estadístico del número de admisiones por urolitiasis, la tasa de complicaciones, hospitalización y el tipo de tratamiento recibido. RESULTADOS: Fueron incluidos 304 pacientes en el análisis. Se observó una reducción significativa en el número global de pacientes ingresados en urgencias por urolitiasis entre 2019 y 2020 (48,8%). Además, con respecto a la elección del tratamiento de los pacientes hospitalizados, se informó un aumento estadísticamente significativo de los procedimientos de extracción de cálculos en comparación con el drenaje urinario en 2020 (p = 0,015). CONCLUSIONES: Durante la pandemia de la COVID-19 en Roma ha habido una reducción significativa de los ingresos en urgencias por urolitiasis. Los pacientes ingresados en el SU tuvieron más complicaciones, necesitaron hospitalización con más frecuencia y en cuanto al manejo clínico, se prefirió la extracción temprana de los cálculos, en vez del drenaje urinario. Todos los urólogos deben ser conscientes de que en los próximos meses podrían enfrentar un mayor número de admisiones por urolitiasis y un manejo de casos más complicados

INTRODUCTION AND OBJECTIVES: We aimed to evaluate how the corona virus disease of 2019 (COVID-19) outbreak influenced emergency department (ED) admissions for urolithiasis, hospitalizations and clinical management of the hospitalized patients. PATIENTS AND METHODS: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. RESULTS. 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8%) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p = 0.015). CONCLUSIONS: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases

The impact of COVID-19 outbreak on urolithiasis emergency department admissions, hospitalizations and clinical management in central Italy: a multicentric analysis. / El impacto de la COVID-19 en las admisiones al servicio de urgencias, hospitalizaciones y manejo clínico de la urolitiasis en el centro de Italia: análisis multicéntrico.

INTRODUCTION AND OBJECTIVES: We aimed to evaluate how the corona virus disease of 2019 (COVID-19) outbreak influenced emergency department (ED) admissions for urolithiasis, hospitalizations and clinical management of the hospitalized patients. PATIENTS AND METHODS: We conducted a multicentric retrospective analysis of ED admissions in three high volume urology departments (one directly involved in COVID-19 patients management and two not involved) in Rome - Italy between March and April 2020 and in the same period of 2019. Statistical analysis was conducted on the number of admissions for urolithiasis, rate of complications, hospitalization and the type of treatment received. RESULTS: 304 patients were included in the analysis. A significant reduction in the global number of patients admitted to ED for urolithiasis between 2019 and 2020 (48.8%) was noted. Moreover, regarding the choice of treatment of hospitalized patients, a statistically significant increase of stone removal procedures versus urinary drainage was reported in 2020 (p = 0.015). CONCLUSIONS: During the COVID-19 pandemic in Rome there has been a significant reduction of emergency admissions for urolithiasis. Patients admitted to ED had more complications, more frequently need hospitalization and regarding clinical management early stone removal was preferred over urinary drainage only. All the urologists should be aware that in the next months they could face an increased number of admissions for urolithiasis and manage more complicated cases.