Background Coronavirus disease 2019 (COVID-19) is associated with a high mortality rate, especially in patients with severe illness. We conducted a systematic review and meta-analysis to assess the potential predictors of mortality in patients with COVID-19. Methods PubMed, EMBASE, the Cochrane Library, and three electronic Chinese databases were searched from December 1, 2019 to April 29, 2020. Eligible studies reporting potential predictors of mortality in patients with COVID-19 were identified. Unadjusted prognostic effect estimates were pooled using the random-effects model if data from at least two studies were available. Adjusted prognostic effect estimates were presented by qualitative analysis. Results Thirty-six observational studies were identified, of which 27 were included in the meta-analysis. A total of 106 potential risk factors were tested, and the following important predictors were associated with mortality: advanced age, male sex, current smoking status, preexisting comorbidities (especially chronic kidney, respiratory, and cardio-cerebrovascular diseases), symptoms of dyspnea, complications during hospitalization, corticosteroid therapy and a severe condition. Additionally, a series of abnormal laboratory biomarkers of hematologic parameters, hepatorenal function, inflammation, coagulation, and cardiovascular injury were also associated with fatal outcome. Conclusion We identified predictors of mortality in patients with COVID-19. These findings could help healthcare providers take appropriate measures and improve clinical outcomes in such patients.
Serum fibrinogen converted to insoluble fibrin by activated thrombin, plays an important role in the coagulation system. Increased fibrinogen considerably influences cancer cell growth, progression and metastasis. In nonsmall cell lung cancer (NSCLC), however, the association between serum fibrinogen concentration and prognosis has not been fully examined. We enlisted 567 operable NSCLC patients in our study. Preoperative serum fibrinogen was measured by the Clauss method. The association of serum fibrinogen concentration with clinical pathological factors and patient outcome was evaluated. Survival analysis indicated that serum fibrinogen was an independent prognostic factor in operable NSCLC. Patients with hyperfibrinogenemia had an elevated risk of disease progression and death compared to patients with normal fibrinogen levels. The hazard ratio was 1.49 (95% confidence interval [CI] 1.07-2.05) for disease progression and 1.64 (95% CI 1.06-2.53) for death. The trend linking increasing fibrinogen levels with risk was also statistically significant for both outcomes (p < 0.05). These analyses were adjusted for patient age, sex, smoking behavior, disease stage, tumor grade and histology. Kaplan-Meier survival curves showed similar results. Preoperative serum fibrinogen is a novel independent prognostic biomarker in operable NSCLC.
Intratumoral hypoxia occurs in many solid tumors, where it is associated with the development of metastatic character. However, the connections between these phenomena are not fully understood. In this study, we define an integrative role for the E3 ubiquitin ligase subunit WSB1. In primary osteosarcomas, increased levels of WSB1 correlated with pulmonary metastatic potential. RNAi-mediated attenuation of WSB1 or disruption of its E3 ligase activity potently suppressed tumor metastasis. Quantitative proteomic and functional analyses revealed that WSB1 ubiquitylates the Rho-binding protein RhoGDI2 and promotes its proteasomal degradation, thereby activating Rac1 to stimulate tumor cell motility and invasion. Our findings show how WSB1 regulates key steps of the metastatic cascade in hypoxia-driven osteosarcoma, and they highlight a candidate therapeutic target to potentially improve the survival of patients with metastatic disease. Cancer Res; 75(22); 4839-51. Ó2015 AACR.
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