Risk factors for mortality of critically ill patients with COVID-19 receiving invasive ventilation.

Rationale: Early invasive ventilation may improve outcomes for critically ill patients with COVID-19. The objective of this study is to explore risk factors for 28-day mortality of COVID-19 patients receiving invasive ventilation. Methods: 74 consecutive adult invasively ventilated COVID-19 patients were included in this retrospective study. The demographic and clinical data were compared between survivors and non-survivors, and Cox regression analysis was used to explore risk factors for 28-day mortality. The primary outcome was 28-day mortality after initiation of invasive ventilation. Secondary outcome was the time from admission to intubation. Results: Of 74 patients with COVID-19, the median age was 68.0 years, 53 (71.6%) were male, 47 (63.5%) had comorbidities with hypertension, and diabetes commonly presented. The most frequent symptoms were fever and dyspnea. The median time from hospital admission to intubation was similar in survivors and non-survivors (6.5 days vs. 5.0 days). The 28-day mortality was 81.1%. High Sequential Organ Failure Assessment (SOFA) score (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.23-1.92; p < 0.001) and longer time from hospital admission to intubation (HR, 2.41; 95% CI, 1.15-5.07; p = 0.020) were associated with 28-day mortality in invasively ventilated COVID-19 patients. Conclusions: The mortality of invasively ventilated COVID-19 patients was particularly striking. Patients with high SOFA score and receiving delayed invasive ventilation were at high risk of mortality.

Effect of dexmedetomidine on delirium during sedation in adult patients in intensive care units: A systematic review and meta-analysis.

STUDY OBJECTIVE: To compare the effect of sedation protocols with and without dexmedetomidine on delirium risk and duration in adult patients in intensive care units (ICUs). DESIGN: A meta-analysis of randomized controlled trials. REVIEW METHODS: We searched the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and ISI Web of Science from inception to September 3, 2020. We included studies comparing the effect of dexmedetomidine-based sedation on delirium risk with non-dexmedetomidine-based sedation in adult patients in ICUs. We pooled the data using a random-effects model using Review Manager 5.2, and assessed publication bias using Stata 11.0. The quality of evidence was rated using the Grading of Recommendations, Assessment, Development and Evaluation system. MAIN RESULTS: We included 36 studies involving 9623 participants. The use of dexmedetomidine was associated with reduced risk of delirium (risk ratio [RR], 0.63; 95% confidence interval [CI], 0.54-0.75; very low-quality evidence), but higher incidences of hypotension and bradycardia during hospital stay. Dexmedetomidine was also associated with shorter durations of ICU stay, hospital stay and mechanical ventilation. Dexmedetomidine did not affect ICU mortality (RR, 1.01; 95% CI, 0.89-1.14; low-quality evidence), hospital mortality (RR, 1.01; 95% CI, 0.91-1.12; very low-quality evidence), or 30-day mortality (RR, 0.77; 95% CI, 0.58-1.01; moderate-quality evidence), or duration of delirium (mean difference, -0.74 days; 95% CI, -1.83 to 0.36 days; very low-quality evidence). We identified publication bias for risk and duration of delirium, length of ICU stay, and hospital stay. CONCLUSIONS: Low- or very low-quality evidence suggests that dexmedetomidine was associated with a clinically-small reduction of delirium risk, ICU/hospital stay and mechanical ventilation duration, but were not associated with improved mortality or shorter delirium duration in ICU patients. These findings were inconclusive because of publication bias, heterogeneity, and limited sample size. Significant adverse effects of dexmedetomidine include hypotension and bradycardia. PROSPERO registration number: CRD42018095358.

Identify the Risk Factors of COVID-19-Related Acute Kidney Injury: A Single-Center, Retrospective Cohort Study.

Background: The kidney is a target organ that could be infected by SARS-CoV-2, and acute kidney injury (AKI) was associated with a higher risk of COVID-19 patients' in-hospital death. However, no published works discussed about the risk factors of COVID-19 related AKI. Methods: We conducted a retrospective cohort study, recruiting COVID-19 inpatients from the Sino-French branch of Tongji Hospital. Demographic, clinical, treatment, and laboratory data were collected and compared. We used univariable and multivariable logistic regression methods to identify the risk factors of COVID-19-related AKI. Results: Of the 116 patients in our study, 12 (10.3%) were recognized as AKI, including 5 (4.3%) in-hospital AKI. Multivariable regression showed increasing odds of COVID-19-related AKI associated with COVID-19 clinical classification (OR = 8.155, 95% CI = 1.848-35.983, ref = non-critical, p = 0.06), procalcitonin more than 0.1 ng/mL (OR = 4.822, 95% CI = 1.095-21.228, p = 0.037), and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 (OR = 13.451, 95% CI = 1.617-111.891, p = 0.016). Conclusions: COVID-19-related AKI was likely to be related to multiorgan failure rather than the kidney tropism of SARS-CoV-2. The potential risk factors of COVID-19 clinical classification, procalcitonin more than 0.1 ng/mL, and eGFR <60 mL/min/1.73 m2 could help clinicians to identify patients with kidney injury at an early stage.

Association of 17-ß Estradiol with Adipose-Derived Stem Cells: New Strategy to Produce Functional Myogenic Differentiated Cells with a Nano-Scaffold for Tissue Engineering.

The increased incidence of stress urinary incontinence (SUI) in postmenopausal women has been proposed to be associated with a reduction in the level of 17-ß estradiol (E2). E2 has also been shown to enhance the multi-differentiation ability of adipose-derived stem cells (ASCs) in vitro. However, studies on the potential value of E2 for tissue engineering in SUI treatment are rare. In the present study, we successfully fabricated myogenically differentiated ASCs (MD-ASCs), which were seeded onto a Poly(l-lactide)/Poly(e-caprolactone) electrospinning nano-scaffold, and incorporated E2 into the system, with the aim of improving the proliferation and myogenic differentiation of ASCs. ASCs were collected from the inguinal subcutaneous fat of rats. The proliferation and myogenic differentiation of ASCs, as well as the nano-scaffold biocompatibility of MD-ASCs, with or without E2 supplementation, were investigated. We demonstrated that E2 incorporation enhanced the proliferation of ASCs in vitro, and the most optimal concentration was 10-9 M. E2 also led to modulation of the MD-ASCs phenotype toward a concentrated type with smooth muscle-inductive medium. The expression of early (alpha-smooth muscle actin), mid (calponin), and late-stage (myosin heavy chain) contractile markers in MD-ASCs was enhanced by E2 during the different differentiation stages. Furthermore, the nano-scaffold was biocompatible with MD-ASCs, and cell proliferation was significantly enhanced by E2. Taken together, these results demonstrate that E2 can enhance the proliferation and myogenic differentiation of ASCs and can be used to construct a biocompatible cell/nano-scaffold. These scaffolds with desirable differentiation cells show promising applications for tissue engineering.

URGCP/URG4 promotes apoptotic resistance in bladder cancer cells by activating NF-κB signaling.

Cisplatin is a well-known chemotherapeutic agent, it could cause DNA damage and induce apoptotic cell death, but the cisplatin resistance also appears, it's important to reveal the mechanisms of cisplatin resistance [1]. URGCP/URG4 is overexpressed in various tumors and plays critical role during tumor development. We found URGCP/URG4 was upregulated in bladder cancer cells and tissues, URGCP/URG4 overexpression increased the resistance to cisplatin-induced apoptosis in bladder cancer, and promoted anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and downregulated Caspase-3 expression, Knockdown of URGCP/URG4 decreased the resistance to cisplatin-induced apoptosis, and inhibited anti-apoptotic genes expression, such as Bcl-2, Survivin, MCL-1, FLIP, and upregulated Caspase-3 expression. Mechanism analysis found URGCP/URG4 activated NF-κB pathway which is a well-known anti-apoptotic pathway and promoted the expression of NF-κB targeted genes. So we speculated URGCP/URG4 regulates cisplatin-induced apoptosis by activating NF-κB pathway. We also analyzed the correlation between URGCP/URG4 expression and clinical clinicopathologic, and found its expression was positively correlated with bladder cancer progression, it can serve as a valuable prognostic factor. In summary, URGCP/URG4 promotes the resistance to cisplatin-induced apoptosis by activating NF-κB pathway, and is an unfavorable prognostic factor for bladder cancer.