PURPOSE Patients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19. METHODS All consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes. RESULTS Five hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST. CONCLUSION A high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

Purpose Ciliary epithelium (CE) of adult mammalian eyes contains quiescent retinal progenitor/stem cells that generate neurospheres in vitro and differentiate into retinal neurons. This ability doesn't evolve efficiently probably because of regulatory mechanisms, such as microRNAs (miRNAs) that control pluripotent, progenitor, and differentiation genes. Here we investigate the presence of Let-7 miRNAs and its regulator and target, Lin28 and Hmga2, in CE cells from neurospheres, newborns, and adult tissues. Methods Newborn and adult rats CE cells were dissected into pigmented and nonpigmented epithelium (PE and NPE). Newborn PE cells were cultured with growth factors to form neurospheres and we analyzed Let-7 , Lin28a, and Hmga2 expression. During the neurospheres formation, we added chemically modified single-stranded oligonucleotides designed to bind and inhibit or mimic endogenous mature Let-7 b and Let-7 c. After seven days in culture, we analyzed neurospheres size, number and expression of Let-7 , Lin28, and Hmga2. Results Let-7 miRNAs were expressed at low rates in newborn CE cells with significant increase in adult tissues, with higher levels on NPE cells, that does not present the stem cells reprogramming ability. The Lin28a and Hmga2 protein and transcripts were more expressed in newborns than adults cells, opposed to Let-7 . Neurospheres presented higher Lin28 and Hmga2 expression than newborn and adult, but similar Let-7 than newborns. Let-7 b inhibitor upregulated Hmga2 expression, whereas Let-7 c mimics upregulated Lin28 and downregulated Hmga2 . Conclusions This study shows the dynamic of Lin28- Let-7 -Hmga regulatory axis in CE cells. These components may develop different roles during neurospheres formation and postnatal CE cells.

The retina is a nerve tissue that can be exposed to environmental and genetic degenerative factors, resulting in visual loss or complete blindness. Although unable to regenerate, some epithelial cells located on the retinal periphery, in the region of the Ciliary Epithelium have been identified as stem / progenitor cells capable of generating new retinal neurons. Despite its ability to regenerate retinal tissue, this capacity does not develop efficiently, indicating the presence of inhibitory mechanisms acting on the regenerative potential of Ciliary Epithelium (CE) cells. Among the currently known inhibitory mechanisms are microRNAs. In this work, we demonstrate that Let-7 family of microRNAs are highly expressed in adult mammalian CE cells, mainly in non-pigmented epithelium cells, which do not have the reprogramming capacity into stem cells. These miRNAs are poorly expressed in newborn animals and accumulate in these cells during tissue maturation / development. The proteins Lin28 and HMGA2, which are important regulators of Let-7 and one of the best described targets in the literature, respectively, showed an inverse expression pattern to Let-7, being highly expressed in newborn animals, with reduced expression with the maturation of the tissue. Ciliary epithelium cells reprogrammed into stem cells (neurospheres) showed similar Let-7 expression to newborns, with higher expression of Lin28a and Hmga2. Finally, the experimental manipulation of Let-7 by mimetic and inhibitors specific agents of this miRNA induced a significant increase of HMGA2 and a slight regulation of Lin-28, suggesting that the regulatory axis Lin-28-Let-7-HMGA may control some of the functions in the cells of the Ciliary Epithelium stem cells.