Background: The World Health Organization has declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the risk factors of illness severity.

Background. The prognostic nutritional index (PNI) has been reported to significantly correlate with poor survival and postoperative complications in patients with various diseases, but its relationship with mortality in COVID-19 patients has not been addressed. Method. A multicenter retrospective study involving patients with severe COVID-19 was conducted to investigate whether malnutrition and other clinical characteristics could be used to stratify the patients based on risk. Results. A total of 395 patients were included in our study, with 236 patients in the training cohort, 59 patients in the internal validation cohort, and 100 patients in the external validation cohort. During hospitalization, 63/236 (26.69) and 14/59 (23.73) patients died in the training and validation cohorts, respectively. PNI had the strongest relationships with the neutrophil-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level but was less strongly correlated with the CURB65, APACHE II, and SOFA scores. The baseline PNI score, platelet (PLT) count, LDH level, and PaO₂/FiO₂ (P/F) ratio were independent predictors of mortality in COVID-19 patients. A nomogram incorporating these four predictors showed good calibration and discrimination in the derivation and validation cohorts. A PNI score less than 33.405 was associated with a higher risk of mortality in severe COVID-19 patients in the Cox regression analysis. Conclusion. These findings have implications for predicting the risk of mortality in COVID-19 patients at the time of admission and provide the first direct evidence that a lower PNI is related to a worse prognosis in severe COVID-19 patients.

BACKGROUND: The World Health Organization (WHO) has recently declared coronavirus disease 2019 (COVID-19) a public health emergency of global concern. Updated analysis of cases might help identify the characteristic and risk factors of the illness severity. METHODS: We extracted data regarding 47 patients with confirmed COVID-19 from Renmin Hospital of Wuhan University between February 1 and February 18, 2020. The degree of severity of COVID-19 patients (severe vs. non-severe) was defined at the time of admission according to American Thoracic Society (ATS) guidelines for community-acquired pneumonia (CAP). RESULTS: The median age was 64.91 years, 26 cases (55.31%) were male of which, and 70.83% were severe cases. Severe patients had higher APACHE II (9.92 vs 4.74) and SOFA (3.0 vs 1.0) scores on admission, as well as the higher PSI (86.13 vs 61.39), Curb-65 (1.14 vs 0.48) and CT semiquantitative scores (5.0 vs 2.0) when compared with non-severe patients. Among all univariable parameters, APACHE II, SOFA, lymphocytes, CRP, LDH, AST, cTnI, BNP, et al were significantly independent risk factors of COVID-19 severity. Among which, LDH was most positively related both with APACHE II (R = 0.682) and SOFA (R = 0.790) scores, as well as PSI (R = 0.465) and CT (R = 0.837) scores. To assess the diagnostic value of these selected parameters, LDH (0.9727) had maximum sensitivity (100.00%) and specificity (86.67%), with the cutoff value of 283. As a protective factor, lymphocyte counts less than 1.045 ⨯ 10 ⁹ /L showed a good accuracy for identification of severe patients with AUC = 0.9845 (95%CI 0.959-1.01), the maximum specificity (91.30%) and sensitivity (95.24%). In addition, LDH was positively correlated with CRP, AST, BNP and cTnI, while negatively correlated with lymphocyte cells and its subsets, including CD3 ⁺ , CD4 ⁺ and CD8 ⁺ T cells (P < 0.01). CONCLUSIONS: This study showed that LDH could be identified as a powerful predictive factor for early recognition of lung injury and severe COVID-19 cases. And importantly, lymphocyte counts, especially CD3 ⁺ , CD4 ⁺ , and CD8 ⁺ T cells in the peripheral blood of COVID-19 patients, which was relevant with serum LDH, were also dynamically correlated with the severity of the disease. FUNDING: Key Project of Shanghai Municipal Health Bureau (2016ZB0202)

The purpose of this study was to evaluate the utility of potential serum biomarkers for acute aortic dissection (AAD) that were identified by isobaric Tags for Relative and Absolute Quantitation (iTRAQ) approaches. Serum samples from 20 AAD patients and 20 healthy volunteers were analyzed using iTRAQ technology. Protein validation was performed using samples from 120 patients with chest pain. A total of 355 proteins were identified with the iTRAQ approach; 164 proteins reached the strict quantitative standard, and 125 proteins were increased or decreased more than 1.2-fold (64 and 61 proteins were up- and downregulated, resp.). Lumican, C-reactive protein (CRP), thrombospondin-1 (TSP-1), and D-dimer were selected as candidate biomarkers for the validation tests. Receiver operating characteristic (ROC) curves show that Lumican and D-dimer have diagnostic value (area under the curves [AUCs] 0.895 and 0.891,P<0.05). For Lumican, the diagnostic sensitivity and specificity were 73.33% and 98.33%, while the corresponding values for D-dimer were 93.33% and 68.33%. For Lumican and D-dimer AAD combined diagnosis, the sensitivity and specificity were 88.33% and 95%, respectively. In conclusion, Lumican has good specificity and D-dimer has good sensitivity for the diagnosis of AAD, while the combined detection of D-dimer and Lumican has better diagnostic value.

Background. Acute aortic dissection (AAD) is a devastating cardiovascular disease with a high rate of disability and mortality. This disease often rapidly progresses to fatal multiple organ hypoperfusion, and the incidence has been increasing in recent years. However, the molecular mechanisms have yet to be clarified. This study is aimed at identifying the differential abundance proteins (DAPs) of aortic arch tissues in patients with AAD by proteomics and select possible proteins involved in AAD pathogenesis. Methods. The fresh aortic arch tissues obtained from 5 AAD patients and 1 healthy donor were analyzed by amine‐reactive tandem mass tag (TMT) labelling and mass spectrometry; then, the pathological sections of another 10 healthy donors and 20 AAD patients were chosen to verify the proteomic results by immunohistochemistry. Results. Of 809 proteins identified by proteomic analysis, 132 differential abundance proteins (DAPs) were screened, of which 100 proteins were significantly downregulated while 32 upregulated. Among 100 downregulated proteins, two proteins with known function, integrin alpha 3 (ITGA‐3) and ITGA‐5, were selected as target proteins involved in AAD pathogenesis. Two target DAPs were verified by immunohistochemisty, and the results showed that the integrated option density (IOD) of ITGA‐3 and ITGA‐5 in AAD patients was significantly lower than that in healthy donors, which were consistent with the proteomic results (P < 0.001). Conclusion. ITGA‐3 and ITGA‐5 represent novel biomarkers for the pathogenesis of AAD and might be a therapeutic target in the future.

Background: Acute type A aortic dissection (AAAD) is a devastating disease. Human aortic smooth muscle cells (HASMCs) exhibit decreased proliferation and increased apoptosis, and integrin α5β1 and FAK are important proangiogenic factors involved in regulating angiogenesis. The aim of this study was to investigate the role of integrin α5β1 and FAK in patients with AAAD and the potential underlying mechanisms. Methods: Aortic tissue samples were obtained from 8 patients with AAAD and 4 organ donors at Zhongshan Hospital of Fudan University. The level of apoptosis in the aortic tissues was assessed by immunohistochemical (IHC) staining and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assays. The expression of integrin α5β1 and FAK was determined. Integrin α5β1 was found to be significantly expressed in HASMCs, and its interaction with FAK was assessed via coimmunoprecipitation (Co-IP) analysis. Proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assays and flow cytometry after integrin α5β1 deficiency. Results: The levels of integrin α5β1 and FAK were both significantly decreased in patients with AAAD. Downregulating the expression of integrin α5β1-FAK strongly increased apoptosis and decreased proliferation in HASMCs, indicating that integrin α5β1-FAK might play an important role in the development of AAAD. Conclusions: Downregulation of integrin α5β1-FAK is associated with increased apoptosis and decreased proliferation in aortic smooth muscle cells and may be a potential therapeutic strategy for AAAD.