脓毒性心肌功能障碍

脓毒症是由感染引起的全身炎症反应综合征,证实有感染灶存在或有高度可疑的感染灶。脓毒症是ICU内重症患者的主要死亡原因,且发病率随着年龄的增长而逐渐增加。近十年来,虽然政府在救治脓毒症患者中投入了巨大的资金和技术支持,但源于脓毒症或脓毒性休克患者的病死率仍高达30%~60%。心血管系统在脓毒症与脓毒性休克的病理生理学中扮演着重要着色。过去的四五十年,开展了很多脓毒性心肌功能障碍方面的研究,也积累了不少循证医学证据。然而,心脏只是心血管系统的一部分。诸如脓毒症患者机体血流动力学的变化系脓毒症对心脏的直接效应,还是脓毒症引起心脏前、后负荷及神经体液因素的变化,继而引起心脏继发改变的研究,至今仍在继续。本文概述了近年来脓毒性心肌功能障碍的研究进展,使读者更全面地了解脓毒性心肌功能障碍的病理生理学改变,合理有效地指导脓毒症和脓毒性休克患者的临床救治。     

连续肾脏替代治疗对脓毒症患者血清中TNF-alpha、IL-6 和IL-8 表达的影响

目的：探讨连续肾脏替代治疗（CRRT）对脓毒症患者血清中肿瘤坏死因子alpha（TNF-alpha）、白介素-6（IL-6）和白介素-8（IL-8）的 影响。方法：将我院2013 年1 月-2014 年6 月间收治的80 例脓毒症患者随机分为观察组与对照组各40 例,两组患者均给予脓毒 症常规治疗,观察组另给予CRRT 治疗。观察比较两组患者治疗前1 天,治疗后24 h,72 h空腹静脉血TNF-alpha、IL-6、IL-8 水平。结 果：观察组治愈率为85.0%（34/40）,明显高于对照组的55.0%（22/40）,差异有统计学意义（P<0.05）;治疗24h、72h 后两组患者 TNF-alpha、IL-6和IL-8 水平均明显下降,其中观察组下降更显著,差异均有统计学意义（P<0.05）。结论：CRRT 能有效降低脓毒症患 者血清中TNF-alpha、IL-6 和IL-8 水平,有助于对炎症反应的正向调节。     

PCT和NT-proBNP在脓毒血症患者生存状况预测中的应用与评价

目的:探究患者降钙素原(PCT)和N端前体脑利钠肽(NT-proBNP)水平在评价脓毒血症患者生存状况的预测价值。方法:本研究于2013年6月~2015年6月期间,选择在我院治疗的脓毒血症患者81例为研究对象,根据患者纳入研究后1个月的生存状况,将所有研究对象分为存活组(55例)和死亡组(26例)。分别测定患者PCT和NT-proBNP水平,并记录患者急性生理与慢性健康状况(APACHEII)评分,通过ROC曲线探究PCT、NT-proBNP对患者生存预后评估的价值。结果:死亡组患者PCT水平及APACHEII评分均显著高于存活组,NT-pro BNP水平显著低于存活组患者(P0.05);PCT与APACHEII评分存在正相关关系(r=0.311;P0.05);NT-pro BNP水平与APACHEII评分存在负相关关系(r=-0.289;P0.05);ROC曲线显示PCT、NT-proBNP水平预测患者生存状况的敏感性(86.23%、82.01%)及特异性(80.89%、87.39%)均较高。结论:脓毒血症患者血清PCT与NT-proBNP水平在预测患者病情严重程度及生存状况方面具有重要价值。     

microRNA参与脓毒症免疫调控机制研究进展

脓毒症是重症监护病房(ICU)患者死亡的重要原因之一,因其高患病率、高死亡率、高治疗费用的特点,以及缺乏有效的救治策略,使它成为人类健康的巨大威胁。免疫炎症反应失衡与脓毒症的发生发展密切相关,但其关键调控机制尚不清楚。微小RNA(micro RNA,mi RNA)在固有免疫反应和适应性免疫反应中起着重要作用。mi RNA通过调控炎症信号通路中关键分子的表达,从而影响脓毒症相关炎症因子的表达。因此,mi RNA可能成为在基因转录后水平诊断和治疗脓毒症的新靶点。     

New-onset atrial fibrillation in sepsis is associated with increased morbidity and mortality

BackgroundThe development of new-onset atrial fibrillation in sepsis has been associated with adverse outcomes.MethodsA systematic literature search was conducted to retrieve articles that investigated the association of new-onset atrial fibrillation in patients diagnosed with sepsis. The primary outcome of interest was the pooled risk ratio (RR) of in-hospital mortality in patients with new-onset atrial fibrillation and sepsis.ResultsSix studies included 3100 patients with new-onset atrial fibrillation in sepsis and 36,900 patients without new-onset atrial fibrillation in sepsis. The pooled RR for in-hospital mortality was 1.45 (95 % CI 1.32–1.60, p < 0.00001, I^2 =24 %). New-onset atrial fibrillation was also associated with increased ICU mortality, ICU and in-hospital length of stay and stroke. New-onset atrial fibrillation occurred more in the elderly, those with a prior history of cardiovascular and respiratory disease, and those with increased severity of illness.ConclusionProspective randomised trials are needed to clarify the significance of new-onset atrial fibrillation in sepsis, optimal treatment strategies for these patients, and the benefit of systemic anticoagulation. Physicians should be aware that new-onset atrial fibrillation in sepsis is not merely an observed temporary arrhythmia but a marker of poor prognosis and should be managed accordingly.     

Lack of new antiinfective agents: Passing into the pre-antibiotic age?

The lack of newly developed antibiotics, together with the increase in multi-resistance of relevant pathogenic bacteria in the last decades, represents an alarming signal for human health care worldwide. The number of severely infected persons increases not only in developing but also in highly industrialized countries. This relates in first line to the most severe form of a bacterial infection, sepsis and the septic shock syndrome, with high mortality on critical care units. No particular anti-sepsis drug is available, and the therapy with conventional antibiotics more and more fails to provide a survival benefit. Due to the fact that the pharmaceutical industry has withdrawn to a high degree from the development of anti-infectious agents, a huge challenge for health care is approaching in the 21 st century. In this article, these problems are outlined and possible alternatives are presented which may be helpful to solve the problem.     

乳酸和APACHE II 评分在评估老年脓毒症患者预后中的应用

目的:研究乳酸和急性生理学及慢性健康状况评分(APACHE Ⅱ评分)对老年脓毒症患者预后的评估作用。方法:老年脓毒症患者96例,按照入院时血乳酸值分成升高者60例,乳酸正常者36例,比较两组的病死率、休克、机械通气和MODS发生率、APACHE Ⅱ评分的区别;根据APACHE Ⅱ评分(<15、15～24、≥25)分为3组,比较每组患者的病情和预后区别。结果:乳酸升高组老年脓毒症患者的机械通气、休克发生率、MODS发生率、APACHE Ⅱ评分明显大于乳酸正常组(P<0.05),病死率明显上升(28.3%vs 2.7%),(P=0.005);随着APACHE Ⅱ评分增高,患者病情逐渐加重,休克发生率和住院病死率明显升高,(P<0.05),患者乳酸水平也明显增高(P<0.05)。结论:血乳酸和APACHE Ⅱ评分都可以评估老年脓毒症患者病情严重和预后,两者升高提示预后差。     

乌司他丁联合连续性血液净化治疗重症脓毒症临床研究

目的：研究连续性血液净化联合乌司他丁对重症脓毒症患者炎症反应的影响及其临床疗效。方法：70例重症脓毒症患者随机分为对照组（n=22例）、CBP组（n=23例）和CBP＋乌司他丁组（n=25例）,其中对照组采用经典治疗方案,CBP组在此基础上加用连续性血液净化,CBP＋乌司他丁组在CBP组基础上加用乌司他丁治疗。观察比较患者病情发展,分别于治疗前后进行血液生化指标、凝血功能检测和动脉血气分析,ELISA法检测血清CRP水平。结果：①与对照组和CBP组相比,CBP＋鸟司他丁纽患者病死率、ICU住院时间、MODS发生率均明显下降（P〈0．05）。②经过治疗,CBP＋乌司他丁组患者APACHEⅡ评分降至15．46±3．96,与对照组（18．06±4．25）和CBP组（17．14±5．55）比较差异有统计学意义（P〈0．05）。③治疗后,患者BUN、HR降低程度依次为CBP＋乌司他丁组〉CBP组〉对照组,组问比较差异有显著性（P〈0．05）,而治疗前后PH值、HCO3-、MAP比较差并不明显（P〉0．05）。④CBP＋乌司他丁纽血清CRP含量下降,WBC数量减少,其变化程度明显大于CBP组和对照组（P〈0．05）。⑤对照组、CBP组和CBP＋乌司他丁组患者PT、TT和APTT时间延长,血小板数量下降,其中CBP＋鸟司他丁组PT、APTT时间短于CBP组和对照组（P〈0．05）。结论：连续性血液净化联合乌司他丁可有效抑制脓毒症患者炎症反应,缓解病情,改善患者预后。     

The effects of CLP-induced sepsis on proliferation and apoptosis of granulosa and theca cells in rat ovary: A histochemical and ultrastructural study

Sepsis is defined as a systemic inflammatory response to infection. This study is aimed to evaluate the effects of experimental sepsis on the proliferation and apoptosis of granulosa and theca cells in the rat ovary.28-day-old immature Wistar-Albino female rats were treated with pregnant mare serum gonadotrophin to develop the first generation of preovulatory follicles. Sepsis was induced by cecal ligation and puncture (CLP). Following in vivo 5-Bromo-2-deoxyuridine (BrdU) labeling, animals were sacrificed and ovaries were embedded in paraffin and Epon. Besides electron microscopic evaluation, BrdU, cleaved caspase-3, p27 immunostaining, and TUNEL labeling were performed.In CLP-operated animals, cleaved caspase-3 immunoreactivity was significantly increased in Graafian follicles. TUNEL and BrdU labeling in the ovarian follicles were not statistically different between CLP and sham-operated rats. In septic animals, p27 immunoreactivity was increased significantly in the nuclei of oocytes and decreased in the cytoplasm of granulosa and theca cells in multilaminar primary follicles compared to the sham group. In ultrastructural evaluation, increased apoptosis was observed in theca interna and granulosa cells in both the early and late stages of follicles in the CLP group.In conclusion, experimentally-induced sepsis leads to apoptosis in ovarian follicles at advanced stages of development. Our data suggest that although sepsis may not cause a potential threat to developing follicles at least in the short term, more severe damage may occur during advanced stages of follicle development.     

Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock

The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.