脓毒症小鼠血清HMGB1与心肌损伤程度、炎症相关因子、BNP及cTnI水平的关系

目的 探讨血清高迁移率族蛋白B1(high mobility group box 1,HMGB1)在脓毒症小鼠心肌损伤中的作用及与心肌细胞炎症因子、血清B型钠尿肽(B-type natriuretic peptide,BNP)和肌钙蛋白(troponin,cTnI)的相关性。 方法 本研究选取6～8周龄、SPF级的昆明系小鼠60只,采用随机数字表法分为模型组、假手术组各30只,采用小鼠盲肠结扎穿孔法建立脓毒症小鼠模型,观察不同时间点小鼠血清HMGB1的水平变化,探讨其与心肌细胞凋亡率、心肌细胞炎症因子、血清B型钠尿肽(BNP)和肌钙蛋白(cTnI)的相关性。 结果 在0 h时刻,模型组和假手术组的血清HMGB1水平、心肌细胞凋亡率差异无统计学意义(P>0.05);在造模后12、24、48及72 h,模型组小鼠的血清HMGB1水平、心肌细胞凋亡率显著高于假手术组,差异均有统计学意义(P<0.05);在造模后48 h,模型组心肌组织中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-10、血清BNP、血清cTnI水平显著高于假手术组(P<0.05);在造模后48 h,模型组心肌组织中TNF-α、IL-6、IL-10、血清BNP、血清cTnI水平与血清HMGB1均呈显著正相关(P<0.05)。 结论 血清HMGB1在脓毒症小鼠中水平升高趋势明显,并且与小鼠心肌损伤具有密切的关系。     

Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

Previous research has reported reduced serum 25-hydroxyvitamin D (25(OH)D) levels is associated with acute infectious illness. The relationship between vitamin D status, measured prior to acute infectious illness, with risk of community-acquired pneumonia (CAP) and sepsis has not been examined. Community-living individuals hospitalized with CAP or sepsis were age-, sex-, race-, and season-matched with controls. ICD-9 codes identified CAP and sepsis; chest radiograph confirmed CAP. Serum 25(OH)D levels were measured up to 15 months prior to hospitalization. Regression models adjusted for diabetes, renal disease, and peripheral vascular disease evaluated the association of 25(OH)D levels with CAP or sepsis risk. A total of 132 CAP patients and controls were 60 ± 17 years, 71% female, and 86% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted odds ratio (OR) 2.57, 95% CI 1.08–6.08) were strongly associated with increased odds of CAP hospitalization. A total of 422 sepsis patients and controls were 65 ± 14 years, 59% female, and 91% Caucasian. The 25(OH)D levels <37 nmol/L (adjusted OR 1.75, 95% CI 1.11–2.77) were associated with increased odds of sepsis hospitalization. Vitamin D status was inversely associated with risk of CAP and sepsis hospitalization in a community-living adult population. Further clinical trials are needed to evaluate whether vitamin D supplementation can reduce risk of infections, including CAP and sepsis.     

miR-16在金黄色葡萄球菌脓毒症中的表达及意义探讨

目的探讨miR-16表达水平与金黄色葡萄球菌脓毒症严重程度的关联性,进一步探讨其潜在的临床意义。方法收集金黄色葡萄球菌脓毒症血液标本共计32例,脓毒性休克、严重脓毒症和一般脓毒症各8例,不同年龄段的健康对照24例;另外,收集革兰氏阴性菌脓毒症血液标本8例。用Trizol液裂解全血后提取microRNA,采用荧光定量PCR测定miR-16在不同组的表达水平(2-△△Ct法),用SPSS 13.0软件分析各组之间的统计学差异。采用SPSS 13.0软件将miR-16定量值与相应CRP和PCT值进行相关性分析。结果 miR-16表达水平与金黄色葡萄球菌脓毒症严重程度呈明显的负关联,各实验组与对照组相比均有统计学差异(P0.001),实验组之间也有统计学差异(P0.01)。miR-16表达水平与CRP和PCT值呈负相关性,相关系数分别为-0.561和-0.769。结论 miR-16表达与金黄色葡萄球菌脓毒症有明显的负关联性,提示其可能作为该菌脓毒症严重程度的标记物。     

The antimicrobial peptide LL37 and its truncated derivatives potentiates proinflammatory cytokine induction by lipoteichoic acid in whole blood

Abstract

Interactions of bacterial and host products in activating the innate immune system is an important area to address. The role of lipoteichoic acid (LTA) in these interactions is particularly important because it is understudied in comparison to other factors. This study evaluated the effect of cationic peptides (CPs) on LTA-induced proinflammatory cytokine production in human whole blood and on purified leukocytes. Four different CPs of truncated derivatives from the known peptides LL37, BPI, and CP207 were used. Two of the CPs (IG33 and LL33), derivatives from LL37, potentiated S. aureus LTA induced TNFα, IL-6 and IL-1β production in whole blood. The release of TNFα was increased 30-fold after 16 hours incubation. Intact LL37 also increased LTA-induced TNFα and IL-1β in a time dependent manner. LTA in combination with either LL33 or IG23 demonstrated a synergistic enhanced TNFα and IL-1β secretion on isolated leukocytes but not on purified monocytes. When complexed with IG23 and LL33, the electrophoretic mobility of LTA was altered in a non-denaturating gel electrophoresis. LTA was disaggregated and migrated more rapidly, suggesting an amphiphilic effect of CPs on LTA. In conclusion, LTA synergizes with LL37 and its truncated derivatives and this may lead to proinflammatory cytokine production and cause problems in sepsis therapy.     

老年脓毒症患者临床特征及预后影响因素

 目的 探讨老年脓毒症患者临床特征及影响预后的危险因素。方法 选取2020年7月-2021年9月某三级甲等医院收治的老年脓毒症患者为研究对象，记录患者的临床及实验室资料，根据患者28天预后情况分为存活组和死亡组，比较各临床指标在两组间的差异，应用二元logistic回归分析法分析影响老年脓毒症患者预后的独立危险因素，进一步绘制受试者工作特征（ROC）曲线，评估不同指标预测患者预后的价值。结果 共纳入121例患者，其中74例为脓毒症，47例为脓毒性休克。存活组92例，死亡组29例。与存活组相比，死亡组患者发生脓毒性休克、合并症个数 ≥ 2的比例均较高（P<0.05）；序贯器官衰竭评估（SOFA）评分和急性生理与慢性健康状况评估（APACHEⅡ）评分也较高，白细胞介素6（IL-6）、胱抑素C（Cys-C）、降钙素原（PCT）、凝血酶原时间（PT）和D -二聚体（D -D）表达水平均增高（均P<0.05），而淋巴细胞绝对计数（ALC）和清蛋白（ALB）表达水平降低（均P<0.01）。二元logistic回归分析显示脓毒性休克、SOFA评分、D -D及Cys-C表达水平是影响老年脓毒症患者28天预后的独立危险因素。ROC曲线分析显示SOFA评分（AUC=0.758）、D -D（AUC=0.774）、Cys-C（AUC=0.650）预测患者的预后均有一定的价值（均P<0.01），与单个指标相比，三个指标的联合检测显示出更高的预测价值（AUC=0.882）。结论 发生脓毒性休克、SOFA评分增高、D -D及Cys-C表达水平增加是导致老年脓毒症患者病死率上升的独立危险因素，SOFA评分、D -D和Cys-C的联合检测可进一步提高脓毒症患者预后的预测价值，为临床治疗和预后评估提供参考依据。     

Therapeutic plasma exchange in the management of sepsis and multiple organ dysfunction syndrome: A report of three cases

Sepsis with multi organ dysfunction syndrome (MODS) is the most common cause of death in patients in noncoronary intensive care units. Currently, there are no specific treatments that reduce mortality in patients with sepsis and MODS. We report three patients who received therapeutic plasma exchange (TPE) for sepsis with MODS who completely recovered. The first patient, a 3‐year‐old male presented with Methicillin‐resistant Staphylococcus aureus‐associated respiratory, renal, coagulation, hepatic, and neurologic dysfunction. After 5 TPEs, the patient fully recovered. The second patient was a 36‐year‐old pregnant female who developed MODS at 22 weeks of gestation. She had developed respiratory, hepatic, renal, cardiovascular, neurologic, and coagulation dysfunction following pneumonia and concurrent urinary tract infection resulting in an intrauterine fetal demise. After 8 TPEs, the patient was discharged home with only mild residual hepatic dysfunction. The third patient, a 50‐year‐old female with a history of seizure disorder, was found unresponsive in over 100°F heat and diagnosed with Staphylococcus aureus‐associated MODS. Her respiratory, coagulation, neurologic, renal, and hepatic systems were affected. The patient underwent 6 TPEs after which she had marked improvement. In conclusion, TPE may be an effective adjunct therapy in MODS by possibly removing toxic mediators and replacing deficient factors using donor plasma. J. Clin. Apheresis 29:127–131, 2014. © 2013 Wiley Periodicals, Inc.     

Renal Transplantation: Relationship between Hospital/Surgeon Volume and Postoperative Severe Sepsis/Graft-Failure. A Nationwide Population-Based Study

Background and objects: We explored the relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure (including death).Methods: The Taiwan National Health Insurance Research Database claims data for all patients with end-stage renal disease patients who underwent kidney transplantation between January 1, 1999, and December 31, 2007, were reviewed. Surgeons and hospitals were categorized into two groups based on their patient volume. The two primary outcomes were severe sepsis and graft failure (including death). The logistical regressions were done to compute the Odds ratios (OR) of outcomes after adjusting for possible confounding factors. Kaplan-Meier analysis was used to calculate the cumulative survival rates of graft failure after kidney transplantation during follow-up (1999-2008).Results: The risk of developing severe sepsis in a hospital in which surgeons do little renal transplantation was significant (odds ratio [OR]; p = 0.0115): 1.65 times (95% CI: 1.12-2.42) higher than for a hospital in which surgeons do many. The same trend was true for hospitals with a low volume of renal transplantations (OR = 2.39; 95% CI: 1.62-3.52; p < 0.0001). The likelihood of a graft failure (including death) within one year for the low-volume surgeon group was 3.1 times higher than for the high-volume surgeon group (p < 0.0001); the trend was similar for hospital volume. Female patients had a lower risk than did male patients, and patients ≥ 55 years old and those with a higher Charlson comorbidity index score, had a higher risk of severe sepsis.Conclusions: We conclude that the risk of severe sepsis and graft failure (including death) is higher for patients treated in hospitals and by surgeons with a low volume of renal transplantations. Therefore, the health authorities should consider exporting best practices through educational outreach and regulation and then providing transparent information for public best interest.     

前列腺素E联合连续肾替代治疗对脓毒症合并急性肾损伤预后的影响

目的：探讨前列腺素E联合连续肾替代治疗（CRRT）对脓毒症合并急性肾损伤（AKI）患者预后的影响。方法：选取89例脓毒症合并AKI患者为研究对象，采用随机数字表法分为对照组（n=44）和观察组（n=45），分别采取CRRT及前列腺素E联合CRRT治疗。比较2组患者预后转归情况，检测并比较2组患者治疗前后血清炎性因子、肾功能及免疫功能指标。结果：观察组ICU治疗时间及住院时间较对照组明显缩短（P<0.05）；对照组死亡14例（31.82%），观察组死亡9例（20.00%），2组患者死亡率无明显差异（P>0.05）。与治疗前比较，治疗后2组血清TNF-α、IL-6、hs-CRP含量降低，BUN、SCr含量升高（P<0.05），且观察组上述指标均低于对照组（P<0.05）。与治疗前比较，治疗后2组CD4⁺/CD8⁺及观察组NK细胞比例及IgG、IgA、IgM含量均明显升高（P<0.05），且观察组高于对照组（P<0.05）。与治疗前比较，治疗后2组Marshall评分、APACHEⅡ评分下降（P<0.05），且观察组低于对照组（P<0.05）。结论：前列腺素E联合CRRT治疗脓毒症合并AKI可显著降低患者炎性因子水平，改善患者肾功能和免疫功能，效果优于单独CRRT治疗。