PAI-1 genetic polymorphisms influence septic patients’outcomes by regulating neutrophil activity

Background:Plasminogen activator inhibitor-1(PAI-1)plays an important role in the pathophysiology of sepsis,but the exact mechanism remains debatable.In this study,we investigated the associations among the serum levels of PAI-1,the incidence of 4G/5G promoter PAI-1 gene polymorphisms,immunological indicators,and clinical outcomes in septic patients.Methods:A total of 181 patients aged 18-80 years with sepsis between November 2016 and August 2018 in the intensive care unit in the Xinhua Hospital were recruited in this retrospective study,with 28-day mortality as the primary outcome.The initial serum level of PAI-1 and the presence of rs1799768 single nucleotide polymorphisms(SNPs)were examined.Univariate logistic regression and multivariate analyses were performed to determine the factors associated with different genotypes of PAI-1,serum level of PAI-1,and 28-day mortality.Results:The logistic analysis suggested that a high serum level of PAI-1 was associated with the rs1799768 SNP of PAI-1(4G/4G and 4G/5G)(Odds ratio[OR]:2.49;95%confidence interval[CI]:1.09,5.68).Furthermore,a high serum level of PAI-1 strongly influenced 28-day mortality(OR 3.36;95%CI 1.51,7.49).The expression and activation of neutrophils(OR 0.96;95%CI 0.93,0.99),as well as the changes in the expression patterns of cytokines and chemokine-associated neutrophils(OR:1.00;95%CI:1.00,1.00),were both regulated by the genotype of PAI-1.Conclusions:Genetic polymorphisms of PAI-1 can influence the serum levels of PAI-1,which might contribute to mortality by affecting neutrophil activity.Thus,patients with severe sepsis might clinically benefit from enhanced neutrophil clearance and the resolution of inflammation via the regulation of PAI-1 expression and activity.

Tip orientation under real-time point-of-care neck ultrasonic monitoring is advantageous in peripherally inserted central catheter procedures:a retrospective cohort study

Background:We analyzed the success and catheter tip malposition rates of peripherally inserted central catheter(PICC)placement using ultrasonic monitoring.Methods:A total of 564 patients were recruited and assigned to either the intervention or control group.In the intervention group,282 patients underwent ultrasound-guided PICC insertion,which helped to identify the position and depth of the catheter tip.From a total of 9000 patients,282 were selectively chosen to receive the traditional method using body surface measurements(control group).The primary endpoint was the success rate;the secondary endpoint was the catheter tip malposition rate as detected by postprocedure chest radiography.Results:In the intervention group,a total of 94 catheters were in a suboptimal position;26 were too deep,68 were too shallow,and 1 was inserted into the subclavian vein,with success and malposition rates of 66.3%and 0.4%,respectively.In the control group,139 catheters were in a suboptimal position;88 were too deep,51 were too shallow,9 were inserted into the jugular vein,and 2 were inserted into the subclavian vein,with success and malposition rates of 46.8%(P<0.001)and 3.9%(P=0.004),respectively.Significant differences were observed in success and malposition rates between the 2 groups.Conclusion:Ultrasound-guided PICC procedures achieved higher success rates and lower malposition rates.

Timely renal replacement therapy linked to better outcome in patients with sepsis-associated acute kidney injury

Background:Recent studies suggest that acute kidney injury(AKI)can be treated with renal replacement therapy(RRT).However,its benefits to patients with sepsis-associated AKI(SA-AKI),which is linked to high mortality and morbidity rates,remain under debate.The aim of this study was to compare the outcomes of different RRT strategies for patients with SA-AKI.Methods:This retrospective study evaluated patients who were admitted to the hospital with sepsis and devel-oped SA-AKI during hospitalization from 1st January 2014 to 31st January 2019.Mortality,renal recovery,and systemic organ function at 90 days following admission were compared between the RRT group(RG)and non-RRT group(NRG),as well as the early-RRT group(EG)and delayed-RRT group(DG).The groups were defined according to the time from admission to RRT initiation(criterion 1,EG1 and DG1)and Kidney Disease Improving Global Outcomes(KDIGO)classification(criterion 2,EG2 and DG2).Categorical and continuous variables were compared using the chi-squared test or Fisher’s exact test and Student’s t-test or Wilcoxon test.Kaplan-Meier curves were constructed to determine the unadjusted survival rates for the different subgroups.Results:A total of 116 patients were included in this study;of those,38 received RRT and 46 expired within 90 days.Among different strategies of RRT,there were no significant differences found in 90-day mortality(RG vs.NRG:𝜒2=0.610,P=0.435;EG1 vs.DG1:𝜒2=0.835,P=0.360;EG2 vs.DG2:𝜒2=0.022,P=0.899)and renal recovery.However,the values of change in sequential organ failure assessment(ΔSOFA)max-min of patients in the EG and RG were significantly higher than those recorded in the NRG(ΔSOFA RG=7.0,ΔSOFA NRG=3.60,ΔSOFA EG1=9.00,ΔSOFA EG2=6.30;P<0.050).Also,the 90-day renal recovery in the EG was better than that noted in the DG with criterion 1(87.5%vs.38.5%,respectively,𝜒2=10.425,P=0.032),suggesting that RRT(especially timely RRT)may be beneficial to the restoration of systemic organ function in patients with SA-AKI.Conclusion:RRT did not reduce the 90-day mortality among patients with SA-AKI.However,timely RRT may benefit the restoration of systemic organ function,thereby improving the quality of life of patients.

Nocturnal urine 6-hydroxy sulfate melatonin is associated with the outcome of subjects with sepsis

Background:It is imperative to identify potential biomarkers for early diagnosis and intervention of severe sepsis.This study investigated the relationship between melatonin secretion and outcome of sepsis after 28-day admission.Methods:Patients with sepsis were randomly divided into an eye mask group and a control group.Blood and urine samples were collected from day 0 to 4.Relevant clinical data and 28-day survival data were obtained.Serum melatonin and urine 6-hydroxy sulfate melatonin(6-SMT)levels were measured.Results:The outcome of sepsis did not differ between the eye mask and control groups.Acute Physiology and Chronic Health Evaluation(APACHE)II and Sequential Organ Failure Assessment(SOFA)scores were significantly higher and monocyte human leukocyte antigen-DR(mHLA-DR),serum melatonin,nocturnal urine 6-SMT,and 24-hour urine 6-SMT levels were significantly lower in the nonsurvivors than in the survivors.The outcome at day 28 after admission was significantly associated with APACHE II and SOFA scores and mHLA-DR,nocturnal urine 6-SMT,and 24-hour urine 6-SMT levels.The areas under the receiver operating characteristic curve were 0.785,0.740,0.774,and 0.858 for APACHE II score,SOFA score,mHLA-DR expression,and nocturnal urine 6-SMT amount,respectively.The optimal thresholds for mHLA-DR and nocturnal urine 6-SMT were 30.13%and 43.60%,respectively.Nocturnal urine 6-SMT level was significantly and positively correlated with mHLA-DR expression.Conclusion:Nocturnal urine 6-SMT level may be a feasible biomarker to predict the outcome of patients with sepsis.The use of a night-time eye mask has no significant effect on the outcome of sepsis.Clinical trials:This study was registered at clinicaltrials.gov(NCT02304224).