[Lymphocyte-to-C-reactive protein ratio in COVID-19: an unexplored tool]. / índice linfocito proteína C reactiva en COVID-19: una herramienta poco explorada.

BACKGROUND: COVID-19 develops severe inflammatory responses that can lead to death. It is essential in a pandemic to have accessible instruments to estimate the prognosis of the disease. The lymphocyte-to-C-reactive protein ratio (LCR) is a predictive biomarker studied in oncology, which could have some advantages in COVID-19 patients in the early stages of the disease. Our objective was to estimate the risk of LCR < 100 and mortality in hospitalized patients with COVID-19. METHODS: hospitalized patients with COVID-19 seen between March to October 2020 were included. The patients were grouped according to LCR < 100 and LCR > 100. A Cox regression model was performed to estimate the association between LCR < 100 and mortality. RESULTS: we included 730 patients with COVID-19. The mean age at diagnosis was 49.9 years (SD 16.8) and 401 (55%) were men. Cox regression model showed an association between LCR <100 and mortality (HR 6.2; 95% CI 1.6 to 23.5; p 0.008), adjusting by age. severe pneumonia, intensive care requirements, and comorbidities. CONCLUSION: LPCR <100 in the initial assessment of hospitalized patients with COVID-19 suggests a higher risk of mortality.

Introducción: El COVID-19 genera respuestas inflamatorias graves que pueden terminar en la muerte. En pandemia resulta fundamental tener instrumentos de f ácil acceso que estimen su evolución. El índice linfocito proteína C reactiva (LPCR) es un marcador pronóstico estudiado en patología oncológica que podría mostrar ventajas en la etapa precoz de la enfermedad por COVID-19. Objetivo: estimar los niveles de LPCR < 100 y su riesgo de mortalidad en pacientes internados con COVID-19. Métodos: Se incluyeron pacientes con COVID 19 que ingresaron a la sala de internación general desde marzo hasta octubre de 2020. Se realizó un modelo de regresión de Cox para estimar la relación entre el LPCR < 100 y mortalidad. Resultados: Se incluyeron 730 pacientes. La edad media de presentación fue 49.9 años (DE 16.8) y 401 (55%) fueron hombres. La mediana de días de internación fue 8 (RIC 6). El modelo de regresión de Cox evidenció asociación entre LPCR <100 y mortalidad (HR 6.2; IC95% 1.6 a 23.5; p 0.008) ajustado por edad, neumonía grave, pases a terapia intensiva, hipertensión arterial, y comorbilidades. Discusión: El LPCR <100 en la evaluación inicial de los pacientes que se internan con COVID-19 podría sugerir mayor riesgo de mortalidad.

Índice linfocito proteína c reactiva en COVID-19: una herramienta poco explorada / Lymphocyte-to-C-reactive protein ratio in COVID-19: an unexplored tool

Resumen Introducción: El COVID-19 genera respuestas inflamatorias graves que pueden terminar en la muerte. En pandemia resulta fundamental tener instrumentos de fácil acceso que estimen su evolu ción. El índice linfocito proteína C reactiva (LPCR) es un marcador pronóstico estudiado en patología oncológica que podría mostrar ventajas en la etapa precoz de la enfermedad por COVID-19. Objetivo: estimar los niveles de LPCR < 100 y su riesgo de mortalidad en pacientes internados con COVID-19. Métodos: Se incluyeron pacientes con COVID 19 que ingresaron a la sala de internación general desde marzo hasta octubre de 2020. Se realizó un modelo de regresión de Cox para estimar la relación entre el LPCR < 100 y mortalidad. Resulta dos: Se incluyeron 730 pacientes. La edad media de presentación fue 49.9 años (DE 16.8) y 401 (55%) fueron hombres. La mediana de días de internación fue 8 (RIC 6). El modelo de regresión de Cox evidenció asociación entre LPCR <100 y mortalidad (HR 6.2; IC95% 1.6 a 23.5; p 0.008) ajustado por edad, neumonía grave, pases a terapia intensiva, hipertensión arterial, y comorbilidades. Discusión: El LPCR <100 en la evaluación inicial de los pacientes que se internan con COVID-19 podría sugerir mayor riesgo de mortalidad.

Abstract Background: COVID-19 develops severe inflammatory responses that can lead to death. It is es sential in a pandemic to have accessible instruments to estimate the prognosis of the disease. The lymphocyte-to- C-reactive protein ratio (LCR) is a predictive biomarker studied in oncology, which could have some advantages in COVID-19 patients in the early stages of the disease. Our objective was to estimate the risk of LCR < 100 and mortality in hospitalized patients with COVID-19. Methods: hospitalized patients with COVID-19 seen between March to October 2020 were included. The patients were grouped according to LCR < 100 and LCR > 100. A Cox regression model was performed to estimate the association between LCR < 100 and mortality. Results: we included 730 patients with COVID-19. The mean age at diagnosis was 49.9 years (SD 16.8) and 401 (55%) were men. Cox regression model showed an association between LCR <100 and mortality (HR 6.2; 95% CI 1.6 to 23.5; p 0.008), adjusting by age. severe pneumonia, intensive care requirements, and comorbidities. Conclusion: LPCR <100 in the initial assessment of hospitalized patients with COVID-19 suggests a higher risk of mortality.

Clinical, genetic and quality-of-life study of a cohort of adult patients with tuberous sclerosis.

BACKGROUND AND OBJECTIVE: Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out. MATERIAL AND METHODS: This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit. RESULTS: Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20-86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population. CONCLUSIONS: Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.

Lupus eritematoso sistémico activo, síndrome deactivación macrofágica y sepsis / Active systemic lupus erythematosus, macrophage activation syndrome and sepsis

El síndrome de activación macrofágica (SAM) es una entidad poco frecuente y grave, caracterizadapor una excesiva activación y proliferación de macrófagos y linfocitos T. Los factoresdesencadenantes son las infecciones, drogas, enfermedades malignas y autoinmunes. Ellupus eritematoso sistémico frecuentemente se asocia al SAM. En la práctica clínica, eldiagnóstico diferencial entre lupus eritematoso sistémico activo, SAM e infección es ungran desafío para el médico internista. Esto se debe a que los signos, síntomas y datos delaboratorio de estas entidades se superponen. El propósito de nuestro trabajo es el reportarlos casos de 2 pacientes con lupus eritematoso sistémico activo, SAM y sepsis...

Macrophage activation syndrome (MAS) is a rare and severe entity characterized by excessive activation and proliferation of macrophages and T-lymphocytes. The usual triggers are infections, drugs, malignancy and autoimmune diseases. Systemic lupus erythematosus is frequently associated with MAS. In clinical practice, differential diagnosis between active systemic lupus erythematosus, MAS and an infection is a great challenge for the internist. This happens because signs, symptoms and laboratory data from these illnesses overlap to a large degree. The purpose of this paper is to present a report on two patients with active systemic lupus erythematosus, MAS, and sepsis...

Clostridium perfringens phospholipase C induced ROS production and cytotoxicity require PKC, MEK1 and NFκB activation.

Clostridium perfringens phospholipase C (CpPLC), also called α-toxin, is the most toxic extracellular enzyme produced by this bacteria and is essential for virulence in gas gangrene. At lytic concentrations, CpPLC causes membrane disruption, whereas at sublytic concentrations this toxin causes oxidative stress and activates the MEK/ERK pathway, which contributes to its cytotoxic and myotoxic effects. In the present work, the role of PKC, ERK 1/2 and NFκB signalling pathways in ROS generation induced by CpPLC and their contribution to CpPLC-induced cytotoxicity was evaluated. The results demonstrate that CpPLC induces ROS production through PKC, MEK/ERK and NFκB pathways, the latter being activated by the MEK/ERK signalling cascade. Inhibition of either of these signalling pathways prevents CpPLC's cytotoxic effect. In addition, it was demonstrated that NFκB inhibition leads to a significant reduction in the myotoxicity induced by intramuscular injection of CpPLC in mice. Understanding the role of these signalling pathways could lead towards developing rational therapeutic strategies aimed to reduce cell death during a clostridialmyonecrosis.

Reactive oxygen species and the MEK/ERK pathway are involved in the toxicity of clostridium perfringens α-toxin, a prototype bacterial phospholipase C.

Clostridium perfringens, the most broadly distributed pathogen in nature, produces a prototype phospholipase C, also called α-toxin, which plays a key role in the pathogenesis of gas gangrene. α-Toxin causes plasma membrane disruption at high concentrations, but the role of intracellular mediators in its toxicity at low concentrations is unknown. This work demonstrates that α-toxin causes oxidative stress and activates the MEK/ERK pathway in cultured cells and furthermore provides compelling evidence that O(2)(-.), hydrogen peroxide, and the OH(.) radical are involved in its cytotoxic and myotoxic effects. The data show that antioxidants and MEK1 inhibitors reduce the cytotoxic and myotoxic effects of α-toxin and demonstrate that edaravone, a clinically used hydroxyl radical trap, reduces the myonecrosis and the mortality caused by an experimental infection with C. perfringens in a murine model of gas gangrene. This knowledge provides new insights for the development of novel therapies to reduce tissue damage during clostridial myonecrosis.