Prognosis Biomarkers of Severe Sepsis and Septic Shock by 1H NMR Urine Metabolomics in the Intensive Care Unit

Early diagnosis and patient stratification may improve sepsis outcome by a timely start of the proper specific treatment. We aimed to identify metabolomic biomarkers of sepsis in urine by ¹H-NMR spectroscopy to assess the severity and to predict outcomes. Urine samples were collected from 64 patients with severe sepsis or septic shock in the ICU for a ¹H NMR spectra acquisition. A supervised analysis was performed on the processed spectra, and a predictive model for prognosis (30-days mortality/survival) of sepsis was constructed using partial least-squares discriminant analysis (PLS-DA). In addition, we compared the prediction power of metabolomics data respect the Sequential Organ Failure Assessment (SOFA) score. Supervised multivariate analysis afforded a good predictive model to distinguish the patient groups and detect specific metabolic patterns. Negative prognosis patients presented higher values of ethanol, glucose and hippurate, and on the contrary, lower levels of methionine, glutamine, arginine and phenylalanine. These metabolites could be part of a composite biopattern of the human metabolic response to sepsis shock and its mortality in ICU patients. The internal cross-validation showed robustness of the metabolic predictive model obtained and a better predictive ability in comparison with SOFA values. Our results indicate that NMR metabolic profiling might be helpful for determining the metabolomic phenotype of worst-prognosis septic patients in an early stage. A predictive model for the evolution of septic patients using these metabolites was able to classify cases with more sensitivity and specificity than the well-established organ dysfunction score SOFA.     

Higher frequency of septic shock in septic patients with the 47C allele (rs4880) of the SOD2 gene

Aim

To analyze the effect of the two different versions of the manganese superoxide dismutase gene (SOD2) on sepsis. The SOD2 gene presents the 47C > T single nucleotide polymorphism (SNP; ID: rs4880) which produces MnSOD with different activities. The − 9Val MnSOD (47T allele) is less efficient than the − 9Ala version (47C allele). During sepsis there are abundance of ROS, high SOD2 expression and excess of H₂O₂ synthesis. High concentrations of H₂O₂ could affect the sepsis scenario and/or the sepsis outcome.

Methods

We determined the 47C > T single nucleotide polymorphism (SNP) frequencies in 529 critically ill patients with or without sepsis, facing outcome. To collect information on population frequencies, we obtained a pilot 47C > T genotypic and allelic frequencies in a random group of 139 healthy subjects.

Results

We compared the 47C allele carriers (47CC + 47CT genotypes) with 47TT homozygotes and noticed a significant association between 47C allele carriers and septic shock in septic patients (P = 0.025). With an adjusted binary multivariate logistic regression, incorporating 47C > T SNP and the main clinical predictors, we showed high SOFA scores [P < 0.001, OR = 9.107 (95% CI = 5.319–15.592)] and 47C allele [P = 0.011, OR = 2.125 (95% CI = 1.190–3.794)] were significantly associated with septic shock outcome. With this information we presented a hypothesis suggesting that this negative outcome from sepsis is possibly explained by effects on cellular stress caused by 47C allele.

Conclusion

In our population there was a significant higher frequency of septic shock in septic patients with the 47C allele of the SOD2 gene. This higher 47C allele frequency in septic patients with negative outcome could be explained by effects of higher activity MnSOD on cellular stress during the sepsis.     

Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

Variation in NOD2 augments Th2- and Th17 responses to myelin basic protein in multiple sclerosis

Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients.     

微小RNA调控脓毒症患者外周血免疫因子表达及其机制研究

目的:探讨脓毒血症患者血清外周白细胞中的微小RNA(mi RNA)表达水平的变化及其在脓毒症患者中的表达意义以及免疫调控的关系。方法:采用流式细胞仪检测外周血CD4+CD25+Treg细胞表达,采用实时定量PCR(RT-PCR)方法检测110例脓毒症患者以及100例正常对照外周血白细胞中mi RNA以及Foxp3 m RNA表达量,酶联免疫吸附法测定TNF-α和IL-10浓度,序贯器官衰竭估计(SOFA)评分系统评价脓毒症患者的严重程度。对mi RNA与白细胞总数、TNF-α、IL-10和SOFA评分之间的相关性进行分析。结果:实验组mi RNA表达水平较对照组显著降低(P0.01),WBC、IL-10水平显著升高(P0.01)。实验组mi RNA表达水平以及SOFA评分、血清TNF-α和IL-10之间呈负相关关系(r值分别为-0.512、-0.623、-0.432,P0.05);与WBC无显著相关性(r=0.215,P0.05)。脓毒症患者外周血Treg表达率和Foxp3m RNA均显著高于对照组(P0.01);随病情严重而升高,轻、中、重度实验组间两两比较差异均有统计学意义(P0.01)。死亡均在重度脓毒症患者中,死亡组Treg、Foxp3 m RNA及IL-10均显著高于存活组(P0.01);mi RNA低于存活组(P0.01)。结论:脓毒症患者外周血的mi RNA表达量显著降低,表达水平在一定程度上可以反应机体的炎症反应情况,同时还可以判断疾病的严重度,且mi RNA参与对Treg细胞增殖的调节,在脓毒症免疫失衡机制中发挥一定的作用。     

C 蛋白基因多态性对脓毒血症患者血小板功能的影响

目的:探讨蛋白C基因突变及基因型频率分布和脓毒血症患者血小板功能及血清TXB2水平的相关性。方法:纳入112例脓毒血症患者,健康人群50例为对照组。采用PCR-RFLP法测定所有受试者蛋白C基因rs 17999808C/A位点和rs1799809位点基因型及突变率。入院24小时内测定脓毒血症患者血小板计数、最大聚集率及血清TXB2水平,并对其进行SOFA评分。结果:病例组和对照组rs17999808位点和rs1799809位点间基因型分布频率无统计学差异(P0.05)。rs 17999808基因型分布C/C占81.48%、C/A占12.96%、A/A占5.55%。rs1799809位点G/G占76.54%、G/C占15.43%、C/C占8.02%。rs17999808位点和rs1799809位点突变率分贝为12.03%、15.74%。病例死亡34例,死亡率30.35%。rs17999808位点突变纯合子患者(A/A)死亡率及SOFA评分明显增高,和野生纯合子及突变杂合子患者差异有统计学意义(P0.05)。rs17999808位点C/C野生纯合子患者血小板计数和TXB2浓度明显高于C/A和A/A患者,血小板聚集率低于后两者,差异有统计学意义(P0.05)。突变纯合子A/A患者较C/C、C/A患者两两相比,差异有统计学意义(P0.05)。rs17999809位点突变和TXB2浓度有相关性(P0.05)。结论:蛋白C基因rs17999808位点突变增加了脓毒血症患者死亡风险,这可能和其改变血小板功能有关。     

Risk of obesity and metabolic syndrome associated with FTO gene variants discloses clinically relevant gender difference among Turks

Gene variations in the fat mass- and obesity-associated gene (FTO) have shown controversial associations with obesity and metabolic syndrome (MetS) in several populations. We explored the association of FTO gene with obesity, MetS, and insulin-related parameters separately in men and women. Two SNPs in the FTO, gene rs9939609 and rs1421085, were genotyped by the Taqman System in 1967 adults (mean age of the whole group 50.1 ± 12.0; 48.4 % male). A random sample of the Turkish Adult Risk Factor cohort was cross-sectionally analyzed. Both SNPs exhibited strong linkage disequilibrium (r² = 0.85) and minor alleles were associated with risk of obesity in women and of MetS in men. Carriers of the rs1421085 C-allele exhibited higher body mass index (BMI) in each gender. Adjusted fasting insulin and HOMA index were significantly higher in C-allele carriers in men alone. Logistic regression analysis demonstrated significantly increased likelihood for obesity in female C-risk allele carriers (OR 1.61; 95 % CI 1.19–2.18), after adjustment for age, smoking status, alcohol usage, physical activity grade and presence of diabetes mellitus. Male C-allele carriers were at increased risk for MetS (OR 1.44; 95 % CI 1.07–1.95), adjusted for age, smoking status, alcohol consumption, and physical activity. Further adjustment for BMI attenuated the MetS risk, indicating interaction between C-allele, gender and BMI. The FTO gene in Turkish adults contributes independently to obesity in women and—by interacting with BMI—to MetS and insulin resistance in men.     

Association of plasma exosomes with severity of organ failure and mortality in patients with sepsis

Current sepsis biomarkers may be helpful in determining organ failure and evaluating patient clinical course; however, direct molecular biomarkers to predict subsequent organ failure have not yet been discovered. Exosomes, a small population of extracellular vesicles, play an important role in the inflammatory response, coagulation process and cardiac dysfunction in sepsis. Nonetheless, the association of plasma exosome with severity and mortality of sepsis is not well known. Therefore, the overall levels of plasma exosome in sepsis patients were assessed and whether exosome levels were associated with organ failure and mortality was evaluated in the present study. Plasma level of exosomes was measured by ELISA. Among 220 patients with sepsis, 145 (66%) patients were diagnosed with septic shock. A trend of increased exosome levels in control, sepsis and septic shock groups was observed (204 µg/mL vs 525 µg/mL vs 802 µg/mL, P < 0.001). A positive linear relationship was observed between overall exosome levels and Sequential Organ Failure Assessment (SOFA) score in the study cohorts (r value = 0.47). When patients were divided into two groups according to best cut‐off level, a statistical difference in 28‐ and 90‐day mortality between patients with high and low plasma exosomes was observed. Elevated levels of plasma exosomes were associated with severity of organ failure and predictive of mortality in critically ill patients with sepsis.     

CD14 C260T promoter polymorphism and the risk of cerebrovascular diseases: a meta-analysis

Cerebrovascular diseases (CVD) are dysfunctions of the brain, resulting from diseases of blood vessels supplying the brain. Atherosclerosis is one of the major underlying causes of CVD, in which inflammation plays a crucial role. One of the inflammatory mechanisms contributing to atherogenesis is the activation of monocytes and macrophages, which could be mediated by the bacterial endotoxin lipopolysaccharide (LPS) via its receptor CD14. The C260T (rs2569190) single-nucleotide polymorphism (SNP) in the promoter region of theCD14 gene was implicated in CVD. To assess the role of this SNP in CVD, a comprehensive meta-analysis of the available genetic data was conducted. All the case-control association studies evaluating the role ofCD14 C260T in CVD were identified. Of these, 7 studies (comprising a total of 1488 patients and 1600 control subjects) were included in this meta-analysis. To measure the strength of genetic association for the gene variant, the odds ratios (ORs) were calculated using both fixed and random effects for comparisons of the alleles, the genotypes, and the dominant and recessive genotype models. The results showed there was no significant association between the T allele of C260T and the risk of CVD under the fixed effects model, OR = 0.99 (95% CI (0.89, 1.09)),P = 0.84; or the random effects model, OR = 0.99 (95% CI (0.88,1.11)),P = 0.83. Similar results were obtained for the homozygotes and the dominant and recessive models. In conclusion, the results of this meta-analysis suggest theCD14 C260T polymorphism is not a risk factor for CVD. However, more studies in ethnically varied populations are needed to evaluate in a reliable manner the role of this SNP in CVD susceptibility.     

降钙素原联合SOFA评分对老年脓毒症患者预后的评估价值

目的:探讨降钙素原(procalcitonin,PCT)联合SOFA评分(sequential organ failure assessment,SOFA)对老年脓毒症患者预后的评估价值。方法:选择首都医科大学宣武医院急诊抢救室收治的105例老年脓毒症患者,入院后给予血常规、血清PCT水平、血气分析及生化全项等检查,并进行急性生理及慢性健康状况评分(acute physiology and chronic health evaluation,APACHEⅡ)和SOFA评分。根据预后将患者分成死亡组27例和存活组78例,比较两组组患者血清PCT水平、白细胞(WBC)、SOFA评分和APACHEⅡ评分,同时比较和分析APACHEⅡ评分、血清PCT水平、SOFA评分、PCT和SOFA评分联合预测患者死亡的受试者工作特征曲线(Receiver operating characteristic curve,ROC)下面积。结果:死亡组患者血清PCT水平、SOFA评分和APACHEⅡ评分均明显高于存活组(P0.05),两组WBC比较无统计学差异(P=0.132);PCT预测患者死亡的ROC曲线下面积为0.694(P=0.001),SOFA预测患者死亡的ROC曲线下面积为0.660(P=0.012),APACHE II评分预测患者死亡的ROC曲线下面积为0.852(P=0.001),大于PCT和SOFA评分(P0.05),PCT和SOFA评分联合预测患者死亡的ROC曲线下面积0.761(P=0.001),与APACHE II评分比较无统计学差异(P=0.139)。结论:血清PCT水平联合SOFA评分预测老年脓毒症患者预后的临床价值与APACHE II评分相当,均明显优于血清PCT水平和SOFA评分单项检测。     

Acute Kidney Injury Enhances Outcome Prediction Ability of Sequential Organ Failure Assessment Score in Critically Ill Patients

Introduction

Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI.

Methods

A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission.

Results

One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI.

Conclusions

For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome.     

Thymidylate synthase polymorphisms are associated to therapeutic outcome of advanced non-small cell lung cancer patients treated with platinum-based chemotherapy

Thymidylate synthase (TYMS) has three polymorphisms that may modulate thymidylate synthase (TS) expression levels: (1) 28 base pairs (bp) variable number tandem repeat (VNTR) (rs34743033); (2) single nucleotide polymorphism (SNP) C>G at the twelfth nucleotide of the second repeat of 3R allele (rs2853542); and (3) 6 bp sequence deletion (1494del6, rs34489327). This study was conducted to evaluate the influence of TYMS polymorphisms on the survival of Portuguese patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based chemotherapy. Our results showed no statistically significant differences between VNTR genotypes; although, considering the SNP C>G, homozygotes 3RG presented a better prognostic at 36 months (p = 0.004) and overall survival (p = 0.003) when compared to 2R3RG patients. Patients with “median/high expression genotypes” demonstrated a better survival at 12 months (p = 0.041) when compared to “low expression genotypes”. Furthermore, 6 bp? carriers (p = 0.006) showed a better survival at 12 months when compared to 6 bp+ homozygotes patients. When analyzing TYMS haplotypes, better survival at 12 months was observed for patients carrying haplotypes with the 6 bp? allele (2R6 bp?; p = 0.026 and 3RG6 bp?; p = 0.045). This is the first report that evaluates the three major TYMS polymorphisms in the therapeutic outcome of NSCLC in Portugal. According to our results, the TYMS polymorphisms may be useful tools to predict which advanced NSCLC patients could benefit more from platinum-based chemotherapy regimens.     

Endothelium Dependent Vasomotion and In Vitro Markers of Endothelial Repair in Patients with Severe Sepsis: An Observational Study

Background

Outcome in sepsis is mainly defined by the degree of organ failure, for which endothelial dysfunction at the macro- and microvascular level is an important determinant. In this study we evaluated endothelial function in patients with severe sepsis using cellular endothelial markers and in vivo assessment of reactive hyperaemia.

Materials and Methods

Patients with severe sepsis (n = 30) and 15 age- and gender- matched healthy volunteers were included in this study. Using flow cytometry, CD34+/KDR+ endothelial progenitor cells (EPC), CD31+ T-cells, and CD31+/CD42b- endothelial microparticles (EMP) were enumerated. Migratory capacity of cultured circulating angiogenic cells (CAC) was assessed in vitro. Endothelial function was determined using peripheral arterial tonometry at the fingertip.

Results

In patients with severe sepsis, a lower number of EPC, CD31+ T-cells and a decreased migratory capacity of CAC coincided with a blunted reactive hyperaemia response compared to healthy subjects. The number of EMP, on the other hand, did not differ. The presence of organ failure at admission (SOFA score) was inversely related with the number of CD31+ T-cells. Furthermore, the number of EPC at admission was decreased in patients with progressive organ failure within the first week.

Conclusion

In patients with severe sepsis, in vivo measured endothelial dysfunction coincides with lower numbers and reduced function of circulating cells implicated in endothelial repair. Our results suggest that cellular markers of endothelial repair might be valuable in the assessment and evolution of organ dysfunction.     

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Introduction

Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.

Methods

The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.

Results

The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.

Conclusion

Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.     

The Polymorphism of YWHAE,a Gene Encoding 14-3-3Epsilon,and Brain Morphology in Schizophrenia: A Voxel-Based Morphometric Study

Background

YWHAE is a possible susceptibility gene for schizophrenia that encodes 14-3-3epsilon, a Disrupted-in-Schizophrenia 1 (DISC1)-interacting molecule, but the effect of variation in its genotype on brain morphology remains largely unknown.

Methods

In this voxel-based morphometric magnetic resonance imaging study, we conducted whole-brain analyses regarding the effects of YWHAE single-nucleotide polymorphisms (SNPs) (rs28365859, rs11655548, and rs9393) and DISC1 SNP (rs821616) on gray matter volume in a Japanese sample of 72 schizophrenia patients and 86 healthy controls. On the basis of a previous animal study, we also examined the effect of rs28365859 genotype specifically on hippocampal volume.

Results

Whole-brain analyses showed no significant genotype effect of these SNPs on gray matter volume in all subjects, but we found significant genotype-by-diagnosis interaction for rs28365859 in the left insula and right putamen. The protective C allele carriers of rs28365859 had a significantly larger left insula than the G homozygotes only for schizophrenia patients, while the controls with G allele homozygosity had a significantly larger right putamen than the C allele carriers. The C allele carriers had a larger right hippocampus than the G allele homozygotes in schizophrenia patients, but not in healthy controls. No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.

Conclusions

These different effects of the YWHAE (rs28365859) genotype on brain morphology in schizophrenia and healthy controls suggest that variation in its genotype might be, at least partly, related to the abnormal neurodevelopment, including in the limbic regions, reported in schizophrenia. Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.     

Neutrophil CD64 expression and serum IL-8: Sensitive early markers of severity and outcome in sepsis

The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24 h of septic onset, Interleukins (IL)-8, -1β, -6, -10, and -12p70, tumor necrosis factor-α (TNF-α), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p < 0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p < 0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p < 0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR = 1.3, p = 0.01 for CD64 and OR = 1.26, p = 0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis.     

脓毒症患者血清炎症因子与SOFA评分的关系研究

目的:探究脓毒症患者血清炎症因子与序贯器官衰竭评估(SOFA)评分的关系,从而有助于评价患者病情严重程度,科学判断预后效果。方法:选择2014年1月至2015年12月期间在本院内接受治疗的脓毒血症患者142例作为研究对象。入院后24 h内患者进行血清炎症因子IL-6、PCT、CRP水平测定,同时进行SOFA评分。按照患者在入院治疗28天内生存结局状况进行分组,分别为死亡组(87例)和存活组(55例),另按照患者合并多器官功能障碍综合症(MODS)与否,分为MODS组(76例)和非MODS组(66例),对比不同组别间IL-6、PCT、CRP及SOFA评分差别;对比不同SOFA评分患者血清IL-6、PCT、CRP水平差异,分析其相关性。结果:IL-6、PCT以及SOFA评分比较,死亡组高于存活组,MODS组高于非MODS组,差异有统计学意义(P0.05);SOFA评分越高,血清IL-6、PCT水平越高,差异有统计学意义(P0.05);SOFA评分升高,患者病死率显著增加,SOFA10分,病死率为78.3%,差异有统计学意义(P0.05);Spearman相关分析结果显示,SOFA评分与血清IL-6水平呈显著正相关关系(r=0.261,P=0.012),与血清PCT水平呈正相关关系(r=0.453,P=0.000),SOFA与CRP水平无相关性(r=0.112,P=0.323)。结论:血清IL-6、PCT水平与SOFA评分具有相关性,可以在脓毒症患者病情严重程度及预后状况判断中作为生物学指标进行常规监测。     

Red Blood Cell Distribution Width during the First Week Is Associated with Severity and Mortality in Septic Patients

Objective

Higher values of red blood cell distribution width (RDW) have been found in non-surviving than in surviving septic patients. However, it is unknown whether RDW during the first week of sepsis evolution is associated with sepsis severity and early mortality, oxidative stress and inflammation states, and these were the aims of the study.

Methods

We performed a prospective, observational, multicenter study in six Spanish Intensive Care Units with 297 severe septic patients. We measured RDW, serum levels of malondialdehyde (MDA) to assess oxidative stress, and tumour necrosis factor (TNF)-α to assess inflammation at days 1, 4, and 8. The end-point was 30-day mortality.

Results

We found higher RDW in non-surviving (n = 104) than in surviving (n = 193) septic patients at day 1 (p = 0.001), day 4 (p = 0.001), and day 8 (p = 0.002) of ICU admission. Cox regression analyses showed that RDW at day 1 (p<0.001), 4 (p = 0.005) and 8 (p = 0.03) were associated with 30-day mortality. Receiver operating characteristic curves showed that RDW at day 1 (p<0.001), 4 (p<0.001), and 8 (p<0.001) could be used to predict 30-day mortality. RDW showed a positive correlation with serum MDA levels at day 1 and day 4, with serum TNF-α levels at days 4 and 8, and with SOFA score at days 1, 4 and 8.

Conclusions

The major findings of our study were that non-surviving septic patients showed persistently higher RDW during the first week of ICU stay than survivors, that RDW during the first week was associated with sepsis severity and mortality, that RDW during the first week could be used as biomarker of outcome in septic patients, and that there was an association between RDW, serum MDA levels, and serum TNF-α levels during the first week.