Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.
Highlights
Dexamethasone, or alternative steroids, are recommended in severe COVID-19.
The use of tocilizumab in COVID-19, with or without steroids, is still controversial.
Risk for mortality was assessed in 186 COVID-19 patients receiving tocilizumab.
Mortality was associated with older age, chronic heart failure and liver disease.
In tocilizumab-treated patients, the additional use of steroids was beneficial.
Objetivo: Identificar los factores de riesgo asociados con la mortalidad a las seis semanas.
Diseño: Estudio prospectivo multicéntrico.
Ámbito: 26 UCI de Andalucía.
Pacientes o participantes: Pacientes ingresados en UCI por neumonía grave por SARS COV 2 en el periodo de tiempo comprendido entre el 8 de marzo y el 30 de mayo.
Intervenciones: Ninguna.
Variables de interés principales: características demográficas, clínicas y escalas de gravedad. Se analizaron tratamientos de soporte, fármacos y la mortalidad.
Resultados: 495 pacientes fueron incluidos, 73 fueron excluidos por incompletos. 422 pacientes fueron incluidos en el análisis final. La mediana de edad fue de 63 años, 305 (72,3%) eran hombres. La mortalidad en la UCI fue: 144/422 34%; mortalidad a los 14 días: 81/422 (19,2%); mortalidad a los 28 días: 121/422 (28,7%); mortalidad a las 6 semanas 152/422 36,5%.
Los factores asociados con la mortalidad a los 42 días fueron la edad, APACHE II, SOFA >6 y LDH al ingreso > 470 U/L, uso de vasopresores, necesidad de técnicas de reemplazo de la función renal, porcentaje de linfocitos a las 72 horas del ingreso en UCI < 6,5%, y trombocitopenia, mientras que el uso de lopinavir/ritonavir fue identificado como un factor protector.
Conclusiones: La edad, gravedad y fracaso orgánico junto con la necesidad de terapias de soporte fueron identificadas como factores predictores de mortalidad a las seis semanas.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.