Search

Background Older adults have been reported to be a population with high-risk of death in the COVID-19 outbreak. Rapid detection of high-risk patients is crucial to reduce mortality in this population. The aim of this study was to evaluate the prognositc accuracy of the Modified Early Warning Score (MEWS) for in-hospital mortality in older adults with COVID-19. Methods A retrospective cohort study was conducted in Wuhan Hankou Hospital in China from 1 January 2020 to 29 February 2020. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive value of MEWS, Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Function Assessment (SOFA), quick Sequential Organ Function Assessment (qSOFA), Pneumonia Severity Index (PSI), Combination of Confusion, Urea, Respiratory Rate, Blood Pressure, and Age ≥65 (CURB-65), and the Systemic Inflammatory Response Syndrome Criteria (SIRS) for in-hospital mortality. Logistic regression models were performed to detect the high-risk older adults with COVID-19. Results Among the 235 patients included in this study, 37 (15.74%) died and 131 (55.74%) were male, with an average age of 70.61 years (SD 8.02). ROC analysis suggested that the capacity of MEWS in predicting in-hospital mortality was as good as the APACHE II, SOFA, PSI and qSOFA (Difference in AUROC: MEWS vs. APACHE II, −0.025 (95% CI [−0.075 to 0.026]); MEWS vs. SOFA, −0.013 (95% CI [−0.049 to 0.024]); MEWS vs. PSI, −0.015 (95% CI [−0.065 to 0.035]); MEWS vs. qSOFA, 0.024 (95% CI [−0.029 to 0.076]), all P > 0.05), but was significantly higher than SIRS and CURB-65 (Difference in AUROC: MEWS vs. SIRS, 0.218 (95% CI [0.156–0.279]); MEWS vs. CURB-65, 0.064 (95% CI [0.002–0.125]), all P < 0.05). Logistic regression models implied that the male patients (≥75 years) had higher risk of death than the other older adults (estimated coefficients: 1.16, P = 0.044). Our analysis further suggests that the cut-off points of the MEWS score for the male patients (≥75 years) subpopulation and the other elderly patients should be 2.5 and 3.5, respectively. Conclusions MEWS is an efficient tool for rapid assessment of elderly COVID-19 patients. MEWS has promising performance in predicting in-hospital mortality and identifying the high-risk group in elderly patients with COVID-19.

The CLP and CASP model as important research tools have been widely utilized in septic OS. In this study, we compare the oxidative stress condition of CLP and CASP rat models. Compared with sham operation group, infection condition and oxidative stress index were significantly different in CLP and CASP groups. Compared with CLP group, there was no significant difference in natural death rate, bacterial colony positive rate, infection condition, center venous oxygen saturation, and serum levels of TNF-α in the CASP group; whereas, MDA decreased significantly at 72 hours, T-SOD increased considerably at 12 and 72 hours after operation in the CASP group. The serum NO significantly decreased at all time-points except at 12 hours post-operation. Together, our study demonstrated the similarity of oxidative stress condition between CLP and CASP models. However, CASP rats had higher serum NO level than CLP rats.

Objectives Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP. Methods We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVAD-CHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1β and IL-18. TUNEL staining was used to detect acinar cell death. Results The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity ofCTSB, NLRP3 and ASC. Conclusion The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.

Macrophages can be alternatively activated by TGF-β1 and high-ambient glucose, in which the role of Smad2 and the crosstalk between ERK and Smad2 pathways are not fully understood. The activation of ERK and Smad2 pathways and the expression of arginase-1 were detected by Western blot. The role of Smad2 and the relationship between ERK and Smad2 pathways were investigated by using biochemical inhibitors. The protein of arginase-1 was significantly overexpressed in RAW264.7 cells stimulated by TGF-β1 and high-ambient glucose, which can be partially blocked by not only U0126 (ERK inhibitor) but also SB431542 (Smad2 inhibitor). Furthermore, simply inhibiting one pathway had no effect on the other pathway. In conclusion, both ERK and Smad2 signal pathways are involved in the activation of macrophages induced by TGF-β1 and high-ambient glucose, while there is no crosstalk shown in the process.