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Objective:To explore the predictive efficacy of prothrombin time (PT) with regarding for the severity and prognosis of septic patients, along with comparing with other routine coagulation parameters.Methods:A retrospective analysis was conducted. The clinical data of 302 septic patients who were admitted to the intensive care unit (ICU) of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology from January 1 to December 31 in 2019 were enrolled. Demographic and basic clinical data were collected. Laboratory data, including PT, activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), D-dimer, fibrin (fibrinogen) degradation product (FDP), antithrombin (AT), platelet count (PLT) at ICU admission were recorded, and sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score within 24 hours of admission to ICU were also collected. What's more, some major clinical events, such as septic shock, disseminated intravascular coagulation (DIC), etc. during ICU stay were also monitored. A follow-up 28 days observation of prognosis was performed. The patients were divided into the septic shock group and the non-septic shock group according to the occurrence of septic shock, and they were divided into the survival group and the non-survival group according to the 28-day prognosis. The differences in terms of above parameters between each two groups were compared. Spearman correlation method was used to analyze the correlation between routine coagulation parameters and SOFA score or APACHEⅡ score. Receiver operator characteristic curve (ROC curve) was plotted to determine the predictive efficacy of each routine coagulation parameter with regarding to predict septic shock and 28-day mortality. Based on the cut-off value of PT, the septic patients were divided into two risk stratifications, and then the major clinical and end point outcome were compared. Kaplan-Meier survival curve analysis was applied to investigate the difference of the 28-day cumulated survival rate based on the different risk stratifications of PT level. Finally, multivariate Logistic regression analysis was used to explore whether prolonged PT level was an independent risk factor for septic shock and 28-day mortality.Results:The 302 patients were all enrolled, including 120 patients with septic shock and 182 patients without. Seventy-five patients died within 28 days, while 227 survived. Comparing with the non-septic shock group or the survival group, the septic shock group or the non-survival group patients both had longer PT, APTT and TT, higher D-dimer, FDP and lower PLT, FIB and AT. Correlation analysis revealed that PT and PLT were better correlated with SOFA score ( r values were 0.503 and -0.524, both P < 0.01), and PT was better correlated with APACHEⅡ score ( r = 0.407, P < 0.01). ROC curve analysis showed that PT had the most powerful predictive efficacy for septic shock and 28-day mortality. The area under the ROC curve (AUC) and 95% confidence interval (95% CI) were 0.831 (0.783-0.879) and 0.739 (0.674-0.805), respectively. The cut-off value were 16.8 s and 16.3 s, respectively, with the sensitivity of 64.2%, 72.0% and the specificity of 89.0%, 70.9%, respectively. Risk stratification based on PT level revealed that the patients with PT > 16.5 s ( n = 103) had higher rate of 28-day mortality, incidence of septic shock and DIC, and score of SOFA and APACHEⅡ comparing to those with PT ≤ 16.5 s ( n = 199). Kaplan-Meier survival curve analysis showed that the 28-day cumulative survival rate was significantly lower in the patients with PT > 16.5 s than those with PT ≤ 16.5 s (52.43% vs. 86.93%; Log-Rank test: χ 2 = 49.428, P < 0.001). Multivariate Logistic regression analysis revealed that PT > 16.5 s was an independent risk factor both for septic shock and 28-day mortality [model 1 (enrolled SOFA score): odds ratio ( OR) and 95% CI were 6.003 (3.040-11.855), 4.842 (2.114-11.089); model 2 (enrolled APACHEⅡ score): OR and 95% CI were 7.675 (4.007-14.702), 5.160 (2.258-11.793)]. Conclusions:Compared with other routine coagulation parameters, PT has the potential best predictive value for evaluating the severity of sepsis and the prognosis. When a patient is diagnosed with sepsis and has a result of PT longer than 16.5 s at ICU admission, the patient may have a higher risk of progression to septic shock and short-term death.
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Objective:To evaluate the diagnostic value of the von Willebrand factor (vWF) GPIb activity to antigen ratio for thrombotic thrombocytopenic purpura (TTP) at acute phase.Methods:A cohort of 93 patients with suspected TTP and admited to our hospitalfrom January 2018 to December 2019 were prospectively enrolled, we analyzed the levels of vWF: GPIb activity and vWF antigen at acute phase, the diagnosis of acquired TTP was defined as ADAMTS13 activity<10%.The PLASMIC score and final diagnosis of included patients were recorded.Results:Twenty-twopatients were diagnosed as TTP, the median (interquartile range) of ADAMTS13 activity were 1.0% (0-7.4%), other diagnoses included hemolytic uremic syndrome (HUS, n=8), severe infection ( n=21), malignancy( n=3), connective tissue disease( n=8), et al. The vWF: GPIb activity, vWF antigen, and ratio of vWF: GPIb activity to antigen were all significantly lower in patients with TTP than in those without ( P<0.05). The ratio of vWF: GPIb activity to vWF antigen <0.75 could yield a sensitivityof 81.8% and a specificity of 95.2% respectively for TTP. In patients with PLASMIC score≥6, 88.9% patients with the ratio of vWF: GPIb activity to vWF antigen <0.75 were confirmed as TTP, and 15.4% patients with the ratio≥0.75 were confirmed as TTP. Conclusions:The ratio of vWF: GPIb activity to vWF antigen based on automaticassays might be useful for differential diagnosis and stratification of TTP at acute phase, especially when the ADAMTS13 assay is not available in time.
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OBJECTIVE@#To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC).@*METHODS@#GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM).@*RESULTS@#Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues.@*CONCLUSIONS@#GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.
Subject(s)
Animals , Female , Mice , Adenoviridae , Apoptosis , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Liver Neoplasms/therapy , Membrane Proteins/genetics , Mice, Inbred BALB C , Oncolytic Virotherapy/methods , Phosphotransferases (Alcohol Group Acceptor)/genetics , Promoter Regions, GeneticABSTRACT
Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus (OA), GP73-SphK1sR-Ad5, on the growth of hepatocellular carcinoma (HCC). Methods: GP73-SphK1sR-Ad5 was constructed by integrating Golgi protein 73 (GP73) promoter and sphingosine kinase 1 (SphK1)-short hairpin RNA (shRNA) into adenovirus serotype 5 (Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1 (E1A) was detected by quantitative real-time PCR (qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK1sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Results: Transfection of GP73-SphK1sR-Ad5 significantly upregulated E1A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.