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.     

Plasma pro- and anti-inflammatory cytokine levels and outcome prediction in unselected critically ill patients

Purpose. To determine the inter-relationships between cytokine levels and physiological scores in predicting outcome in unselected, critically ill patients. Methods. To this end, 127 patients (96 men), having a mean ± SD age of 45 ± 20 years, with a wide range in admission diagnoses (medical, surgical, and multiple trauma patients) were prospectively investigated. Severity of critical illness and organ dysfunction were graded by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, respectively. Blood samples were drawn on admission in the ICU to determine pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10. The main outcome measure was 28-day mortality. Results. Overall, 88 patients survived and 39 patients died. Univariate logistic regression analysis showed that SOFA, APACHE II, IL-8, IL-6, and IL-10 on admission in the ICU were related to mortality. Multiple logistic regression analysis in the entire cohort of critically ill patients revealed that SOFA (OR = 1.341, p < 0.001) and IL-6 (OR = 1.075, p = 0.01) constituted independent outcome predictors. receiver operator characteristics curve analysis showed that SOFA, APACHE II, and IL-6 had the highest area under the curve values. IL-6 correlated with APACHE II (r_s = 0.44, p < 0.0001) and SOFA (r_s = 0.40, p < 0.0001) scores. Conclusions. In mixed ICU patients cytokine concentrations on admission in the ICU represent independent outcome predictors in the presence of disease severity scores.     

Primary cilium: an elaborate structure that blocks cell division?

A primary cilium is a microtubule-based membranous protrusion found in almost all cell types. A primary cilium has a “9 + 0” axoneme that distinguishes this ancient organelle from the canonical motile “9 + 2” cilium. A primary cilium is the sensory center of the cell that regulates cell proliferation and embryonic development. The primary ciliary pocket is a specialized endocytic membrane domain in the basal region. The basal body of a primary cilium exists as a form of the centriole during interphase of the cell cycle. Although conventional thinking suggests that the cell cycle regulates centrosomal changes, recent studies suggest the opposite, that is, centrosomal changes regulate the cell cycle. In this regard, centrosomal kinase Aurora kinase A (AurA), Polo-like kinase 1 (Plk1), and NIMA related Kinase (Nek or Nrk) propel cell cycle progression by promoting primary cilia disassembly which indicates a non-mitotic function. However, the persistence of primary cilia during spermatocyte division challenges the dominate idea of the incompatibility of primary cilia and cell division. In this review, we demonstrate the detailed structure of primary cilia and discuss the relationship between primary cilia disassembly and cell cycle progression on the background of various mitotic kinases.     

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。     

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。     

Alteration of plasma phospholipid fatty acid profile in patients with septic shock

In septic shock patients, alterations of plasma phospholipid fatty acid profile have never been described. The purpose of this monocentric, non-interventional, observational prospective study was to describe this fatty acid profile in the early phase of septic shock in intensive care unit. Thirty-seven adult patients with septic shock were included after the first day of stay in intensive care unit, before any form of artificial nutritional support. Plasma phospholipid fatty acid composition was determined by gas chromatography. All biological data from patients with septic shock were compared with laboratory reference values. Patients presented hypocholesterolemia and hypertriglyceridemia. They had low concentrations of phospholipid fatty acids specifically n-6 and n-3 polyunsaturated fatty acids (PUFAs) with a high n-6/n-3 ratio. Plasma phospholipid PUFA concentrations were strongly correlated with cholesterolemia. PUFAs/SFAs (saturated fatty acids) and PUFAs/MUFAs (monounsaturated fatty acids) ratios were low because of low percentage of n-6 and n-3 PUFAs and high percentage of SFAs and MUFAs. Low levels of plasma long chain PUFAs (≥20 carbons) were significantly associated with mortality at 28th day. In conclusion, plasma phospholipid FA profile of septic patients is very characteristic, close to that of acute respiratory distress syndrome and mortality is associated with long chain PUFA decrease. This profile could be explained by numerous non-exclusive physio-pathological processes 1) an activation of hepatic de novo lipogenesis that could contribute to hepatic steatosis, 2) an elevated adipose tissue lipolysis, 3) an increased free radical attack of FA by oxidative stress, 4) an over-production of inflammatory lipid mediators.     

复杂性腹腔感染的病原菌分布及APACHEⅡ评分、SOFA评分联合PCT检测的预后评估价值研究

摘要 目的：探讨复杂性腹腔感染的病原菌分布及急性生理和慢性健康状况Ⅱ（APACHEⅡ）评分、序贯器官衰竭（SOFA）评分联合降钙素原（PCT）检测的预后评估价值。方法：选择合肥市第二人民医院2016年1月至2020年10月收治的80例复杂性腹腔感染患者,分析腹腔细菌的病原菌分布情况。根据患者预后情况分为生存组（n=45）、死亡组（n=35）,比较两组APACHEⅡ评分、SOFA评分、PCT、C反应蛋白（CRP）、白细胞计数（WBC）、中性粒细胞比例、血乳酸水平。分析患者预后的影响因素,并应用受试者工作特征（ROC）曲线分析APACHEⅡ评分、SOFA评分、PCT及三者联合检测对预后的预测价值。结果：80例复杂性腹腔感染患者共培养出病原菌112株,其中革兰氏阳性球菌20株（占比17.86%）,革兰氏阴性杆菌64株（占比57.14%）,真菌28株（占比25.00%）。死亡组白色念珠菌、铜绿假单胞菌感染比例显著高于存活组,大肠杆菌感染比例显著低于存活组（P<0.05）,死亡组血清APACHEⅡ评分、SOFA评分、PCT、CRP、血乳酸水平显著高于存活组,WBC、中性粒细胞比例显著低于存活组（P<0.05）。多因素Logistic回归分析显示,铜绿假单胞菌感染、白色念珠菌感染、APACHEⅡ评分≥20分、SOFA评分≥14分、PCT≥7.00 ng/mL、CRP≥100.00 mg/L、血乳酸≥4 mmol/L、WBC<6.00×10⁹、中性粒细胞比例<80.00%是患者死亡的危险因素（P<0.05）。ROC曲线分析显示APACHEⅡ评分、SOFA评分联合PCT检测对患者预后评估的敏感度为95.93%,特异度为92.38%。结论：复杂性腹腔感染以革兰氏阴性杆菌为主,其死亡危险因素较多,联合检测APACHEⅡ评分、SOFA评分及PCT评估预后价值较高。