Prognostic Systems To Predict Outcome In Severe Sepsis: A Primary Study

Part 1Comparison of three different score systems MODS,SOFA and LODS on predicting outcome of severe sepsisObjective To compare three different score systems MODS score,SOFA score and LODS score on predicting outcome of severe sepsis.Methods Four hundred three patients admitted to ICU with a diagnosis of severe sepsis were enrolled into the present study.Admission value and maximum value of MODS score,SOFA score,LODS score and Acute Physiology and Chronic Health Evaluation(APACHE)Ⅱwere calculated.The theoretic mortality of severe sepsis was estimated using these three score systems and was compared to the actual hospital mortality.The predictive value of the three score systems on outcome of severe sepsis was assessed by the areas under the receiver operating characteristic curves(AUC).Results The AUC of admission values in predicting hospital mortality were 0.811 for LODS,0.787 for SOFA,0.725 for MODS and 0.770 for APACHEⅡ.The maximum values showed better power for discrimination than the admission values in all three score systems(p<0.001).The power of the admission value or the maximum value of LODS score and SOFA score to discriminate mortality of severe sepsis was better than that of MODS score,respectively(p<0.001).However,no significant difference was observed between LODS score and SOFA score in terms of mortality prediction (p>0.05).The AUC value for APACHEⅡshowed much lower power when compared to LODS score(p=0.038).However,there is no significant difference in AUC value among APACHEⅡ,SOFA score and MODS score systems(p>0.05).Conclusion All of the three score systems show a good predictive power,while the maximum value of LODS score appears the highest discrimination power to predict the outcome of severe sepsis.Part 2Association study of SNPs within the promoter region of protein C gene with severe sepsis in Chinese Han populationObjective To investigate whether two functional SNPs within the promoter region of protein C gene is associated with severe sepsis in Chinese Han population.Method In a case-control study,the genotypes of -1641A/G and -1654C/T in 240 patients with severe sepsis and 323 healthy controls were assayed by means of direct sequencing.Meanwhile,haplotype was estimated using StatSNPs program.The association between the genomic variations(allele,genotype and haplotype) and severe sepsis were analyzed using(?)~2-test and logistic regression.The magnitude of association were reflected by Odds Ratio.Results SNPs -1641A/G and -1654C/T in the two studied groups were in Hardy-Weinberg equilibrium.Neither -1641A/G nor -1654C/T alone was associated with the incidence and outcome of severe sepsis.Three haplotypes AC,GC and AT were estimated in the cohort.After Bonferroni correction for multiple comparisons,AC haplotype was significantly associated with the fatal outcome of severe sepsis(p=0.008, OR 1.739,95%CI 1.165-2.595),which was confirmed by multiple logistic regression analysis(p=0.024,OR 2.090,95%CI 1.101-3.967).Compared to patients without carrying AC haplotype,the AC haplotype carriers showed higher SOFAmax scores (10.3±5.2 vs.9.0±4.5;p=0.014) and more hepatic dysfunction(p=0.004,OR 2.270, 95%CI 1.312-3.930).Conlusion These findings suggest that protein C haplotype -1641A/-1654C is associated with organ dysfunction and is an independent risk factor for the fatal outcome of severe sepsis in Chinese Han population.Part 3Association study of genomic variations withinα7 nicotinic acetylcholine receptor gene with susceptibility and outcome ofsevere sepsis in Chinese Han populationObjective To investigate whether SNPs inα7 nAChR gene is associated with the susceptibility and outcome of severe sepsis in Chinese Han population.Method In a case-control study,the genotypes of -1831G/T,-1512T/G,-1313 A/G and -194G/C withinα7 nAChR gene were assayed in 240 patients with severe sepsis and 323 healthy controls by means of PCR-RFLP and direct sequencing.Haplotype was estimated using StatSNPs program.The association between the genomic variations (allele,genotype and haplotype) and severe sepsis were analyzed using(?)~2-test and logistic regression.The magnitude of association were reflected by Odds Ratio.Results All of the assayed SNPs in the two groups were in Hardy-Weinberg equilibrium.The distributions of allelic frequencies and genotype frequencies between controls and patients with severe sepsis as well as between surviving patients and nonsurviving patients showed no significant difference(all,p>0.05 ).Four common haplotypes GTAG,TTGG,GGGG and GTGC were estimated in the studied cohort.The distributions of haplotype frequencies in the defined groups were also similar.Conlusion The genomic variations withinα7 nAChR gene were not associated with the susceptibility and outcome of severe sepsis.These findings suggest that genomic variations withinα7 nicotinic acetylcholine receptor gene do not play a major role in the susceptibility to and outcome of severe sepsis,and may not serve as a genetic marker for predisposition to severe sepsis.