Early Warning Factors of Death in COVID-19 Patients.

The infectious coronavirus disease 2019 (COVID-19) has spread all over the world and been persistently evolving so far. The number of deaths in the whole world has been rising rapidly. However, the early warning factors for mortality have not been well ascertained. In this retrospective, single-centre cohort study, we included some adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Renmin Hospital of Wuhan University who had been discharged or had died by Apr. 8, 2020. Demographic, clinical and laboratory data at admission were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable analysis, Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve to explore the early warning factors associated with in-hospital death. A total of 159 patients were included in this study, of whom 86 were discharged and 73 died in hospital. Hypertension (52.1% vs. 29.1%, P=0.003) and coronary heart disease (28.8% vs. 12.8%, P=0.012) were more frequent among non-survived patients than among survived patients. The proportions of patients with dyspnoea (67.1% vs. 25.6%, P<0.001), chest distress (58.9% vs. 26.7%, P<0.001) and fatigue (64.4% vs. 25.6%, P<0.001) were significantly higher in the non-survived group than in the survived group. Regression analysis with the Cox proportional hazards mode revealed that increasing odds of in-hospital death were associated with higher IL-6 (odds ratio 10.87, 95% CI 1.41-83.59; P=0.022), lactate (3.59, 1.71-7.54; P=0.001), older age (1.86, 1.03-3.38; P=0.041) and lower lymphopenia (5.44, 2.71-10.93; P<0.001) at admission. The areas under the ROC curve (AUCs) of IL-6, lymphocyte, age and lactate were 0.933, 0.928, 0.786 and 0.753 respectively. The AUC of IL-6 was significantly higher than that of age (z=3.332, P=0.0009) and lactate (z=4.441, P<0.0001) for outcome prediction. There was no significant difference between the AUCs of IL-6 and lymphocyte for outcome prediction (z=0.372, P=0.7101). It was concluded that the potential risk factors of higher IL-6, lactate, older age and lower lymphopenia at admission could help clinicians to identify patients with poor prognosis at an early stage.

MiR-28 inhibits cardiomyocyte survival through suppressing PDK1/Akt/mTOR signaling.

MicroRNAs play critical roles in regulating cell survival under multiple pathological conditions of heart diseases. Oxidative stress-induced apoptosis contributes greatly to heart ischemia-reperfusion injury. Herein, we describe a novel regulatory role of miR-28 on the survival of cardiomyocytes. We show that miR-28 was upregulated in cardiomyocytes treated with hydrogen peroxide (H2O2). MiR-28 gain of function sensitized cell apoptosis, whereas miR-28 loss of function partially rescued cell apoptosis induced by H2O2. Importantly, we observed a significant reduction in Akt/mammalian target of rapamycin (mTOR) signaling activity after miR-28 treatment. Luciferase activity assay and western blot analysis both revealed that, phosphoinositide-dependent kinase-1 (PDK1), which is critical for Akt activation, was directly and negatively modulated by miR-28. Our results therefore indicate that miR-28 regulates oxidative stress-induced cell apoptosis in heart muscle cells, which possibly involves a PDK1/Akt/mTOR-dependent mechanism. MIR-28 could serve as a critical therapeutic target to diminish oxidative stress-induced cell death in the heart.

Protective effect of propofol and its relation to postoperation recovery in children undergoing cardiac surgery with cardiopulmonary bypass.

The aim of this study was to investigate the effect of propofol and its relation to postoperation recovery in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Twenty ASA class I-II children with congenital heart disease undergoing cardiac surgery were randomly allocated to a propofol group (n = 10) or a control group (n = 10). Blood samples were collected at five time points: before operation (T (0)), before the start of CPB (T (1)), 25 min after the aorta was cross-clamped (T (2)), 30 min after release of the aortic cross-clamp (T (3)), and 2 h after the cessation of CPB (T (4)). The myocardial samples were collected at the time of incubation into the right atrium before CPB and at 30 min after reperfusion. After CPB, propofol significantly suppressed the increase of the serum lactate dehydrogenase (LDH), creatine phosphokinase (CK), and interleukin-6 (IL-6) levels and the decrease of the serum superoxide dismutase (SOD) level. In addition, propofol inhibited the increase of myocardial nuclear factor-κB (NF-κB) expression and inflammatory cells infiltration after CPB. Furthermore, propofol significantly shortened the tracheal extubation time. In conclusion, propofol exerts a protective effect and improves postoperation recovery through its antioxidant and anti-inflammatory actions in children undergoing cardiac surgery with CPB.

Comparison of the effects of propofol and midazolam on inflammation and oxidase stress in children with congenital heart disease undergoing cardiac surgery.

PURPOSE: To investigate and compare the effects of propofol and midazolam on inflammation and oxidase stress in children with congenital heart disease undergoing cardiac surgery. MATERIALS AND METHODS: Thirty-two ASA class I-II children with congenital heart disease undergoing cardiac surgery were randomly divided into two groups: propofol combined with low dose fentanyl (PF group, n = 16) and midazolam combined with low dose fentanyl (MF group, n = 16). Tracheal extubation time and length of Intensive Care Unit (ICU) stay were recorded. Blood samples were taken before operation (T0), at 2 h after release of the aorta cross-clamp (T3) and at 24 h after operation (T4) to measure interleukin 6 (IL-6), IL-8, superoxide dismutase (SOD) and malondialdehyde (MDA) levels. Myocardium samples were collected at 10-20 min after aorta cross-clamp (T1) and at 10-20 min after the release of the aorta cross-clamp (T2) to detect heme oxygenase-1 (HO-1) expression. RESULTS: Tracheal extubation time and length of ICU stay in PF group were significantly shorter than those of the MF group (p < 0.05, respectively). After cardiopulmonary bypass, IL-6, IL-8 and MDA levels were significantly increased, and the SOD level was significantly reduced in both two groups, but PF group exhibited lower IL-6, IL-8 and MDA levels and higher SOD levels than the MF group (p < 0.05, respectively). The HO-1 expression in the PF group was significantly higher than that in MF group at the corresponding time points (p < 0.05, respectively). CONCLUSION: Propofol is superior to midazolam in reducing inflammation and oxidase stress and in improving post-operation recovery in children with congenital heart disease undergoing cardiac surgery.

[Cardioprotective effects of propofol and midazolam in children with congenital heart diseases undergoing open heart surgery].

OBJECTIVE: To observe the cardioprotective effects of propofol and midazolam in children with congenital heart diseases undergoing open heart surgery. METHODS: Thirty-two children with cyanotic congenital heart diseases of ASA classes I - II were randomly divided into 2 equal groups: propofol combined with low dose fentanyl group (Group PF) and midazolam combined with low dose fentanyl group (Group MF). The changes of hemodynaics, ECG, SpO2, nasopharyngeal and rectal temperatures were monitored continuously. The time of tracheal extubation and ICU staying time were recorded. Venous blood samples were collected when the venous channel was opened (T(0)), 2 h after declamping of the aorta (T(4)), and 24 h after operation (T(5)) to detect the plasma cardiac troponin I (cTnI). Myocardium samples were collected 10 - 20 min after aorta cross-clamp (T(2)), and 10 - 20 min after declamping of the aorta (T(3)) to undergo immunohistochemistry to observe the expression of heme oxygenase-1 (HO-1). RESULTS: The tracheal time of Group GF was 14.17 h, significantly shorter than that of Group MF (23.65 h, P < 0.05), and the ICU staying time of Group GF was 30.17 h, significantly shorter than that of Group MF (49.47 h, P < 0.05). The plasma cTnI level at T(4) of Group GF was 97 ng/ml +/- 33 ng/ml, significantly higher than those at T(0) (0.17 ng/ml +/- 0.10 ng/ml, P < 0.01) and T(5) (23 ng/ml +/- 13 ng/ml, P < 0.01). The plasma cTnI level at T(4) of Group MF was138 ng/ml +/- 56 ng/ml, significantly higher than those at T(0) (0.62 ng/ml +/- 0.96 ng/ml, P < 0.01) and T(5) (24 ng/ml +/- 6 ng/ml, P < 0.01). And the plasma cTnI levels at T(5) of these 2 groups were both significantly higher than those at T(0) (both P < 0.01), however, there was no significant difference in the plasma cTnI level at any time point between these 2 groups. The grey values of HO-1 in cardiac muscle cells at T(2) of Groups GF and MF were 182.2 +/- 0.8 and 193.5 +/- 1.4, both significantly higher than those at T(3) (125.6 +/- 2.1 and 145.5 +/- 7.4 respectively, both P < 0.01), and the grey values of HO-1 in cardiac muscle cells at T(2) and T(3) of Group MF were both significantly higher than those of Group GF (both P < 0.05). CONCLUSION: Both propofol and midazolam have protective effects for the children with congenital heart diseases undergoing open heart surgery, and propofol is superior to midazolam in the cardioprotection.