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.     

早期液体复苏对感染性休克患者血流动力学的影响

目的：早期液体复苏对感染性休克患者血流动力学的影响。方法：选取2012年2月-2013年2月我院ICU收治的26例感染性休克患者作为研究对象,随机分为对照组和试验组,各13例。两组患者均采用PICCO监测,并根据早期复苏目标导向（Earlygoaldirectedtherapy,EGDT）进行早期液体复苏治疗。对照组和试验组复苏液分别为林格液和6％羟乙基淀粉130／0．4氯化钠溶液。分别于复苏开始时（Oh）、8h和24h收集患者的血流动力学参数。结果：两组患者CO及PAWP水平均随着时间的延长下降,而CI、CVP及SVR水平均随着时间的增加上升。除对照组CI外,与开始复苏（oh）相比较试验组和对照组的C0、CI、CVP、SVR及PAWP与开始复苏（O小时）相比较均有显著差异（P值均〈0．05）。经重复测量资料的．方差分析进行比较发现,与对照组相比较,试验组CVP和SVR上升水平及PAWP下降水平明显,差异具有统计学意义（P值均〈0．05）。结论：感染性休克患者使用6％羟乙基淀粉130／0．4氯化钠溶液进行复苏,能更好的改善患者的血流动力学指标。     

Effects of corticotropin-releasing hormone on proopiomelanocortin derivatives and monocytic HLA-DR expression in patients with septic shock

Little is known about interactions between immune and neuro-endocrine systems in patients with septic shock. We therefore evaluated whether the corticotropin-releasing hormone (CRH) and/or proopiomelanocortin (POMC) derivatives [ACTH, β-endorphin (β-END), β-lipotropin (β-LPH), α-melanocyte stimulating hormone (α-MSH) or N-acetyl-β-END (Nac-β-END)] have any influences on monocyte deactivation as a major factor of immunosuppression under septic shock conditions. Sixteen patients with septic shock were enrolled in a double-blind, cross-over and placebo controlled clinical study; 0.5 μg/(kg_bodyweight h) CRH (or placebo) were intravenously administered for 24 h. Using flow cytometry we investigated the immunosuppression in patients as far as related to the loss of leukocyte surface antigen-DR expression on circulating monocytes (mHLA-DR). ACTH, β-END immunoreacive material (IRM), β-LPH IRM, α-MSH and Nac-β-END IRM as well as TNF-α and mHLA-DR expression were determined before, during and after treatment with CRH (or placebo). A significant correlation between plasma concentration of α-MSH and mHLA-DR expression and an inverse correlation between mHLA-DR expression and TNF-α plasma level were found. Additionally, a significant increase of mHLA-DR expression was observed 16 h after starting the CRH infusion; 8 h later, the mHLA-DR expression had decreased again. Our results indicate that the up-regulation of mHLA-DR expression after CRH infusion is not dependent on the release of POMC derivatives. From the correlation between plasma concentration of α-MSH and mHLA-DR expression, we conclude that in patients with septic shock the down-regulation of mHAL-DR expression is accompanied by the loss of monocytic release of α-MSH into the cardiovascular compartment.     

液体负平衡对感染性休克合并急性肺损伤患者早期复苏及预后的影响

目的:探讨液体负平衡对感染性休克合并急性肺损伤(ALI)患者早期复苏及预后的影响。方法:将2010年1月~2014年9月我院急诊外科收治的84例感染性休克合并ALI的患者随机分为治疗组和对照组,每组各42例患者。治疗组采用出入量负平衡方式进行液体管理,对照组采用出入量平衡方式进行液体管理。观察和比较两组治疗前后氧合指数(PaO_2/FiO_2)、中心静脉压(CVP)、平均动脉压(MAP)、心指数(CI)、血管外肺水指数(ELWI)及APACHEⅡ评分的变化,记录和比较两组的机械通气时间、ICU住院时间、多器官功能障碍综合征(MODS)的发生率及28 d的病死率。结果:入院后3d、7d,治疗组的MAP较对照组明显降低,ELWI、PaO_2/FiO_2则明显升高(P0.05);治疗前、治疗后6h,两组的APACHEⅡ评分比较均无显著性差异(P0.05),而治疗组治疗后24h、48h的APACHEⅡ评分较对照组则明显降低(P0.05);与对照组比较,治疗组的机械通气时间、ICU住院时间显著缩短,MODS发生率明显降低(P0.05)。结论:在维持循环稳定和保证器官灌注的前提下,液体负平衡有助于减轻感染性休克合并ALI患者的心肺损伤,促进患者早期复苏,改善患者的预后。     

限制性补液复合去甲肾上腺素对脓毒性休克患者血流动力学及氧代谢的影响

目的:探讨限制性补液复合去甲肾上腺素对脓毒性休克患者血流动力学及氧代谢的影响。方法:将62例脓毒性休克患者按照液体复苏策略随机分为限制性液体复苏(治疗组)和常规液体复苏(对照组),每组各31例。观察和比较复苏前后血流动力学指标、氧代谢指标的变化,记录两组低血压、弥散性血管内凝血(DIC)、多器官功能障碍综合征(MODS)、急性呼吸窘迫综合症(ARDS)的发生率及2周病死率。结果:治疗后1 h、3 h、6 h,两组患者CVP、MAP明显升高,HR明显下降(P0.05);治疗后3 h、6 h,治疗组MAP明显低于对照组(P0.05),而两组HR、CVP比较差异均无统计学意义(P0.05)。治疗后1 h、3 h、6 h,两组患者PaCO_2、PaO_2、SaO_2、PaO_2/Fi O_2均不同程度改善,治疗组治疗后3 h、6 h PaO_2、PaO_2/Fi O_2明显高于对照组(P0.05)。治疗后3 d,治疗组MODS的发生率较对照组显著降低(P0.05),而两组低血压、ARDS、DIC及2周病死率均无显著性差异(P0.05)。结论:限制性液体复合小剂量去甲肾上腺素对脓毒性休克患者有助于维持血流动力学稳定,改善全身氧代谢,减少并发症的发生,改善预后。     

床旁超声联合血乳酸对感染性休克患者容量反应性的预测价值分析

目的:研究床旁超声与血乳酸(LAC)联合应用于感染性休克患者容量反应性预测中的效能。方法:选取2015年10月~2017年10月于我院接受治疗的120例感染性休克患者进行研究。对所有患者均开展补液试验,并按照试验结果的差异将其分作反应组63例和无反应组57例。对两组人员均实施床旁超声检查以及LAC水平检测,并对比相关指标水平。通过Pearson相关性分析明确感染性休克患者床旁超声指标与LAC水平的关系。采用受试者工作特征(ROC)曲线分析床旁超声与LAC联合预测上述患者容量反应性的效能。结果:两组补液后平均动脉压(MAP)、中心静脉压(CVP)均高于补液前(P<0.05),反应组补液前下腔静脉呼吸变异率(△IVC)、主动脉峰值流速呼吸变异率(△VpeakAO)、肱动脉最大速度变异率(△VpeakBA)高于补液后及无反应组(P<0.05)。两组补液后LAC水平均低于补液前,且反应组低于无反应组(P<0.05)。经Pearson相关性分析可得:感染性休克患者LAC水平与△IVC、△VpeakAO、△VpeakBA均呈正相关(P<0.05)。经ROC曲线分析可知:床旁超声联合LAC预测感染性休克患者容量反应性的曲线下面积、灵敏度、特异度以及约登指数均高于床旁超声和LAC单独预测。结论:感染性休克患者补液后LAC水平降低,床旁超声联合LAC预测感染性休克患者容量反应性的效能较高,具有一定的临床应用价值。     

布鲁杆菌性化脓性关节炎1例

布鲁菌病是系统性感染性疾病,临床表现多样,在非流行区易被忽视。本病以骨关节受累常见,关节症状多数为反应性关节炎,以单关节化脓性关节炎为首发表现的病例少见。本文报道1例布鲁杆菌性化脓性单膝关节炎的临床表现和诊疗情况。     

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。     

Recent improvements in the development of A<Subscript>2B</Subscript> adenosine receptor agonists

Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A₁, A_2A, A_2B and A₃ (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A_2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A_2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A_2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N ⁶-, C²-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA₁ K _i = 1050 nM, hA_2A K _i = 1550 nM, hA_2B EC₅₀ = 82 nM, hA₃ K _i > 5 μM) and its 2-chloro analogue 23 (hA₁ K _i = 3500 nM, hA_2A K _i = 4950 nM, hA_2B EC₅₀ = 210 nM, hA₃ K _i > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA_2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA₁, hA_2A, hA₃ EC₅₀ > 10 μM; hA_2B EC₅₀ = 3 nM) is currently under preclinical-phase investigation for treating coronary artery disorders and atherosclerosis.     

血必净注射液联合替加环素治疗脓毒症休克患者的临床疗效观察

目的:研究血必净注射液联合替加环素治疗脓毒症休克患者的临床疗效。方法:选取2015年9月至2016年8月我院收治的86例脓毒症休克患者,根据患者入院顺序分为观察组和对照组,42例每组。对照组使用血必净注射液完成治疗,观察组在此基础上加以替加环素。比较两组患者治疗前后APACHEII评分、尿量、血清LAC、血尿素氮(BUN)、肌酐(SCr)、炎性因子及心肌酶水平的变化。结果:治疗后,两组患者APACHEII评分均较治疗前显著降低(P0.05),尿量均较治疗前显著增加(P0.05),和对照组相比,观察组的APACHEII评分较低(P0.05),尿量较多(P0.05);两组患者血清LAC、BUN、SCr、IL-6、CRP、TNF-α、CK-MB、c Tn I、LDH水平较治疗前显著降低(P0.05),且观察组的以上指标水平较对照组显著降低(P0.05)。结论:血必净注射液联合替加环素治疗脓毒症休克患者能有效改善患者病情严重程度,提高患者心肾功能并抑制炎症反应,临床疗效较单用血必净注射液更好。