[Prognostic value of PCSK9 and blood lipid in patients with sepsis].

OBJECTIVE: To investigate the prognostic value of proprotein convertase subtilisin/kexin type 9 (PCSK9) and blood lipid indexes in patients with sepsis. METHODS: Patients with sepsis or septic shock who were ≥ 18 years old and met the Sepsis-3.0 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to October 2021 were enrolled. Healthy adults at the same period were selected as healthy control group. Baseline characteristics, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) score were recorded. Venous blood samples were collected within 24 hours after diagnosis, and serum PCSK9 was determined by enzyme-linked immunosorbent assay (ELISA) at 1, 3 days and 5 days. Meanwhile, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG) and lipoprotein A were detected. The differences of each index between sepsis group (28-day death group and survival group) and healthy control group were compared. Meanwhile, the indexes of patients with different severity and 28-day prognosis in sepsis group were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCSK9 and blood lipid for the prognosis of sepsis. Multivariate Logistic regression was used to analyze the influencing factors for the prognosis of sepsis, and the Kaplan-Meier survival curve at 28th day was drawn. RESULTS: There were 50 patients in sepsis group (including 19 patients with sepsis, 31 patients with septic shock) and 27 patients in healthy control group. In the sepsis group, 19 patients died and 31 patients survived within 28 days. The serum PCSK9 in the sepsis group was significantly higher than that in the healthy control group [µg/L: 223.09 (198.47, 250.82) vs. 188.00 (165.27, 214.90), P < 0.01], and HDL-C, LDL-C, TC and lipoprotein A were significantly lower than those in the healthy control group [HDL-C (mmol/L): 0.82±0.35 vs. 1.45±0.24, LDL-C (mmol/L): 1.53 (1.14, 2.47) vs. 2.89 (2.55, 3.19), TC (mmol/L): 2.03 (1.39, 2.84) vs. 4.24 (3.90, 4.71), lipoprotein A (g/L): 8.80 (5.66, 17.56) vs. 27.03 (14.79, 27.03), all P < 0.01]. PCSK9 in the sepsis death group was higher than that in the survival group [µg/L: 249.58 (214.90, 315.77) vs. 207.01 (181.50, 244.95), P < 0.01], and the HDL-C, LDL-C and TC were lower than those in the survival group [HDL-C (mmol/L): 0.64±0.35 vs. 0.93±0.30, LDL-C (mmol/L): 1.32±0.64 vs. 2.08±0.94, TC (mmol/L): 1.39 (1.01, 2.23) vs. 2.69 (1.72, 3.81), all P < 0.01]. With the progression of the disease, the PCSK9 in the sepsis death group and the survival group was significantly lower than that within 1 day of diagnosis (all P < 0.05). ROC curve analysis showed that PCSK9 had higher predictive value of 28-day death than HDL-C, LDL-C, TC [area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.748 (0.611-0.885) vs. 0.710 (0.552-0.868), 0.721 (0.575-0.867), 0.702 (0.550-0.854)]. Multivariate Logistic regression analysis showed that PCSK9 was an independent risk factor affecting the 28-day prognosis of sepsis (ß value was 1.014, P = 0.020). Kaplan-Meier survival curve analysis showed that when PCSK9 ≥ 208.97 µg/L, with the increase of PCSK9, the 28-day survival rate of sepsis patients decreased significantly. CONCLUSIONS: PCSK9, HDL-C, LDL-C and TC can all predict the 28-day prognosis of patients with sepsis. The prognostic value of PCSK9 is the highest. PCSK9 is an independent risk factor affecting the prognosis of sepsis. In the early stage of the disease, PCSK9 may have a good predictive value for the prognosis of sepsis. When PCSK9 ≥ 208.97 µg/L, the 28-day survival rate decreased significantly.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

[The effect of early goal lactate clearance rate on the outcome of septic shock patients with severe pneumonia].

OBJECTIVE: To observe the clinical effects of 10%, 30% lactate clearance rate and early goal-directed therapy (EGDT) as 6-hour resuscitation goals directing treatment in septic shock patients with severe pneumonia. METHODS: In this randomized, perspective study, septic shock patients with severe pneumonia were divided into control group and experimental group, which included 10% lactate clearance rate group and 30% lactate clearance rate group, adopting random number method. The control group was treated with 6-hour EGDT strategy, and the experimental groups were treated with 10% lactate clearance rate protocol and 30% lactate clearance rate protocol respectively, beside the EGDT. RESULTS: There were 19 patients in control group, and 43 patients in experimental group, which included 22 patients in 10% lactate clearance rate group and 21 patients in 30% lactate clearance rate group. Patients were well matched by basic features. After 48 hours, the acute physiology and chronic health evaluation II (APACHE II ) score of both 10% lactate clearance rate group (13.76 ± 6.00, P < 0.05) and 30% lactate clearance rate group (13.60 ± 6.18, P < 0.05) were lower than that of control group (18.15 ± 6.62). There were no differences in time of mechanical ventilation (hours) between control group and experimental group (10% group 136.90 ± 100.02, 30% group 97.00 ± 75.20, control group 152.32 ± 96.51, P > 0.05). The length in intensive care unit (ICU, days) of 10% and 30% lactate clearance rate groups were significantly shorter than control group (10% group 7.94 ± 6.00, 30% group 7.51 ± 3.99, control group 11.31 ± 5.97, both P < 0.05). The three groups had no differences in 7-day mortality rate (10% group 18.18%, 30% group 14.29%, control group 21.05%, all P > 0.05), but the 28-day mortality of 10% and 30% lactate clearance rate groups were significantly lower than control group (10% group 36.36%, 30% group 28.57%, control group 63.16%), especially in 30% lactate clearance rate group (P < 0.05). CONCLUSION: For the septic shock patients with severe pneumonia, prompt archiving EGDT strategy and 6-hour lactate clearance more than 30% were associated with an optimal outcome.

[Effect of continuous blood purification on endothelial cell function in patients with severe sepsis].

OBJECTIVE: To investigate the effect of continuous blood purification (CBP) in patients with severe sepsis, and to evaluate the change in endothelial cell function in patients with severe sepsis during CBP therapy. METHODS: According to random principle, 45 patients were divided into control group (n=22) and CBP group (n=23). All patients of both groups received routine treatment according to international guidelines 2008 for management of severe sepsis, but the patients in the CBP group also received continuous veno-venous hemofiltration (CVVH) for 72 hours, the ultrafiltrate volume was 40 ml×kg(-1)×h(-1). Blood gas analysis was done before and 24 hours and 72 hours after CVVH therapy. The activated protein C (APC), soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor (vWF) were measured. Also the length of stay in intensive care unit (ICU), time of mechanical ventilation, and death rate of patients in 28 days were observed. RESULTS: Compared with control group, the length of stay in ICU (days) and length of use of ventilator (days) in CBP group were shorter (9.12±3.07 vs. 11.64±4.82, 5.52±3.48 vs. 8.02±5.25, both P<0.05), and the death rate in 28 days was lower [13.0% (3/23) vs. 40.9% (9/22), P<0.05]. After therapy, patients in CBP group showed more reduction in the APACHEII score compared with control group (3.96±4.07 vs. 1.68±2.43, P<0.05). Patients in control group showed less change in APC, sICAM-1 and vWF. APC in CBP group increased at 72 hours, and sICAM-1 and vWF of CBP group respectively decreased at 24 hours or 72 hours, while the APC (µg/L) and vWF (mg/L) at 72 hours showed significant change compared with that of the control group (15.12±7.57 vs. 10.01±5.83, 1.58±0.73 vs. 2.64±1.34, P<0.05 and P<0.01). In patients who died in 28 days (12 patients) there were little changes in APC, sICAM-1 and vWF, while patients who lived for 28 days (33 patients), showed significantly more reduction in sICAM-1 (µg/L) and vWF (mg/L, 61.03±45.58 vs. 104.64±71.08, 1.88±1.21 vs. 2.70±0.95,both P<0.05). The APC value (µg/L) was increased after treatment in patients who survived for 28 days (13.55±7.11 vs. 10.37±7.60, P<0.01). CONCLUSION: CBP therapy can protect endothelial cell function and ameliorate dysfunction, and it reduces the severity of the severe sepsis as well as improves the outcome of patients with severe sepsis.