RESUMO
COVID-19 pandemic is a continuing ongoing emergency of public concern. Early identification of markers associated with disease severity and mortality can lead to a prompter therapeutic approach. The present study conducted a multivariate analysis of different markers associated with mortality in order to establish their predictive role. Confirmed cases of 697 patients were examined. Demographic data, clinical symptoms and comorbidities were evaluated. Laboratory and imaging severity scores were reviewed. A total of 133 (19.1%) out of 697 patients succumbed during hospitalization. Obesity was the most common comorbidity, followed by hypertension, diabetes, coronary heart disease and chronic kidney disease. Compared with the survivor patients, non-survivors had a higher prevalence of diabetes, chronic kidney disease and coronary heart disease, as well as higher values of laboratory markers such as neutrophil-lymphocyte ratio (NLR), D-dimer, procalcitonin, IL-6 and C Reactive protein (CRP) and respectively high values of imaging severity scores. Multivariate regression analysis showed that high values of the proposed markers and chest computerized tomography (CT) severity imaging score were predictive for in hospital death: NLR [hazard ratio (HR): 3.127 confidence interval (CI) 95: 2.137-4.576]; D-dimer [HR: 6.223 (CI 95:3.809-10.167)]; procalcitonin [HR: 4.414 (CI 95:2.804-6.948)]; IL-6 [HR: 3.344 (CI 95:1.423-7.855)]; CRP [HR:2.997 (CI 95:1.940-4.630)]; and CT severity score [HR: 3.068 (CI 95:1.777-5.299)]. Laboratory markers and imaging severity scores could be used to stratify mortality risk in COVID-19 patients.
RESUMO
Knowledge on acute myeloid leukemia pathogenesis and treatment has progressed recently, but not enough to provide ideal management. Improving the prognosis of acute myeloid leukemia patients depends on advances in molecular biology for the detection of new therapeutic targets and the production of effective drugs. The CRISPR/Cas9 technology allows gene insertions and deletions and it is the first step in investigating the function of their encoded proteins. Thus, new experimental models have been developed and progress has been made in understanding protein metabolism, antitumor activity, leukemic cell maintenance, differentiation, growth, apoptosis, and self-renewal, the combined pathogenetic mechanisms involved in leukemogenesis. The CRISPR/Cas9 system is used to understand drug resistance and find solutions to overcome it. The therapeutic progress achieved using the CRISPR/Cas9 system is remarkable. FST gene removal inhibited acute myeloid leukemia cell growth. Lysine acetyltransferase gene deletion contributed to decreased proliferation rate, increased apoptosis, and favored differentiation of acute myelid leukemia cells carrying MLL-X gene fusions. The removal of CD38 gene from NK cells decreased NK fratricidal cells contributing to increased efficacy of new CD38 CAR-NK cells to target leukemic blasts. BCL2 knockout has synergistic effects with FLT3 inhibitors. Exportin 1 knockout is synergistic with midostaurin treatment in acute myeloid leukemia with FLT3-ITD mutation. Using the results of CRISPR/Cas9 libraries and technology application will allow us to get closer to achieving the goal of curing acute myeloid leukemia in the coming decades.
