Critical illness polyneuropathy and critical illness myopathy are frequent complications of severe illness that involve sensorimotor axons and skeletal muscles, respectively. Clinically, they manifest as limb and respiratory muscle weakness. Critical illness polyneuropathy/myopathy in isolation or combination increases intensive care unit morbidity via the inability or dififculty in weaning these patients off mechanical ventilation. Many patients continue to suffer from decreased exercise capacity and compromised quality of life for months to years after the acute event. Substantial progress has been made lately in the understanding of the pathophysiology of critical illness polyneuropathy and myopathy. Clinical and ancillary test results should be carefully interpreted to differentiate critical illness polyneuropathy/myopathy from similar weaknesses in this patient population. The present review is aimed at providing the latest knowledge concerning the pathophysiology of critical illness polyneuropathy/myopathy along with relevant clinical, diagnostic, differentiating, and treatment information for this debilitat-ing neurological disease.

Objective To explore whether the amount of lipocalin-2 in the biofluid could reflect the onset of sepsis-induced acute lung injury (ALI) in mice.
Methods Lipopolysaccharide (LPS, 10 mg/kg) injection or cecal ligation and puncture (CLP) was performed to induce severe sepsis and ALI in C57 BL/6 male mice randomly divided into 5 groups (n=10 in each group):group A (intraperitoneal LPS injection), group B (intravenous LPS injection via tail vein), group C (CLP with 25%of the cecum ligated), group D (CLP with 75%of the cecum ligated), and the control group (6 sham-operation controls plus 4 saline controls). All the mice received volume resuscitation. Measurements of pulmonary morphological and functional alterations were used to identify the presence of experimental ALI. The expressions of lipocalin-2 and interleukin (IL)-6 in serum, bronchoalveolar lavage fluid (BALF), and lung tissue were quantified at both protein and mRNA levels. The overall abilities of lipocalin-2 and IL-6 tests to diagnose sepsis-induced ALI were evaluated by generating receiver operator characteristic curves (ROC) and computing area under curve (AUC).
Results In both group B and group D, most of the“main features”of experimental ALI were reproduced in mice, while group A and group C showed septic syndrome without definite evidence for the presence of ALI. Compared with septic mice without ALI (group A+group C), lipocalin-2 protein expression in septic mice with ALI (group B+group D) was significantly up-regulated in BALF (P<0.01) and in serum (P<0.01), and mRNA expression boosted in lung tissues (all P<0.05). Lipocalin-2 tests performed better than IL-6 tests in recognizing sepsis-induced ALI cases, evidenced by the larger AUC of the former (BALF tests, 0.8800 versus 0.6625;serum tests, 0.8500 versus 0.7000). Using a dual cutoff system to diagnose sepsis-induced ALI, BALF lipocalin-2 test exhibited the highest positive likelihood ratio (13.000) and the lowest negative likelihood ratio (0.077) among the tests of lipocalin-2 and IL-6 in blood and BALF. A statistically significant correlation was found between lipocalin-2 concentration in BALF and that in serum (Spearman r=0.8803, P<0.0001).
Conclusions Lipocalin-2 expression is significantly up-regulated in septic ALI mice compared with those without ALI. Lipocalin-2 tests with a dual cutoff system could be an effective tool in distinguishing experimental ALI cases.

Sepsis与感染性休克的急诊救治及流程优化

Sepsis及感染性休克是临床常见的综合症,与患者预后密切相关.早期救治对Sepsis及感染性休克至关重要.急诊医师在早期诊断Sepsis、 评价危险因素和早期复苏方面均起到至关重要的作用.目前证据表明,"Sepsis的集束化治疗"能够改善此类患者预后,2018年4月"拯救Sepsis运动"再次更新了相关推荐意见,提出了"1 h集束化治疗目标",这对急诊医师提出了更高的要求.本文拟从救治流程、 具体处理及可能的政策指导方面讨论Sepsis及感染性休克的急诊优化治疗,以期提高指南依从性和治疗质量,由此改善此类患者的预后.

Sepsis与感染性休克的治疗:争议中前行

Sepsis和感染性休克是导致重症患者死亡的主要原因之一.随着对Sepsis病理生理机制和临床诊治研究的逐渐深入,"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"自2004年起每4年对SSC指南更新一次,使临床诊疗逐渐趋于规范.近10余年的数据显示,Sepsis患者的病死率稳定且呈显著下降趋势.2016年更新的SSC指南在抗感染治疗方面遭遇到了美国感染病学会(Infectious Disease Society of America,IDSA)的挑战,其在官方期刊Clin Infect Dis发表公开立场声明,不再支持SSC指南.这一举动给临床医生借鉴和应用2016年版SSC指南带来很大困惑.深入了解两大学会对于SSC指南争议的本质至关重要,只有回归争议本质,理清分歧的基点,才能更好地使用指南,使其真正成为临床诊治Sepsis和感染性休克的重要参考.

Sepsis并非感染:支持"拯救Sepsis运动"

Sepsis不同于感染,是机体对感染的反应失控而导致的危及生命的器官功能障碍.Sepsis的重点在于器官功能障碍而非感染,这可能是美国感染病学会(Infectious Disease Society of America,IDSA)与"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"在重症感染认知上的分歧.对于Sepsis而言,筛查至关重要,可更早地启动集束性治疗策略,从而改善患者预后.Sepsis的理念来源于循证医学证据及大数据研究结果,二者奠定了其坚实的理论基础.本文根据IDSA提出的争议话题,从SSC角度,阐述重症医学对Sepsis本质的认知.

感染诊疗应得到重视:支持美国感染病学会

Sepsis是导致重症患者死亡的重要原因.近年来,随着临床和基础研究的不断发展,人们对于Sepsis定义、 诊断以及治疗认识不断深入,患者病死率持续下降.每4年颁布一次并更新的"拯救Sepsis运动(Surviving Sepsis Campaign,SSC)"指南受到国际广泛重视.2016年版SSC指南,在对Sepsis和感染性休克重新定义、 重新制定诊断标准的基础上,于2017年1月正式发布.然而,2017年11月,美国感染病学会(Infectious Disease Society of America,IDSA)即在其官方期刊Clin Infect Dis发表公开声明,对2016年版SSC指南中关于感染诊疗的推荐意见提出质疑.本文站在IDSA的立场,尝试从Sepsis概念、 诊断及治疗3个方面解读IDSA声明,探讨Sepsis中的"感染"问题.

高迁移率族蛋白B1在创伤免疫功能紊乱中的作用及其调节机制

Objective To investigate the potential effect of high mobility group box 1 protein (HMGB1) on host immune response and its molecular regulation mechanism as well as its interventional pathway following major burns/trauma. Methods With both animal experiments and clinical investigation, serial studies were conducted to observe the effects of HMGB1 on changes in immune function of T lymphoeytes, dendritic cells, and macrophages both in vivo and in vitro. Results It was found that thermal injury or trauma induced a delayed and persistent increase in HMGB1 expression as well as its release in various tissues.HMGB1 formation could markedly influence the cell-mediated immunity, including the changes in T lymphocytes, dendritic cells, and macrophages following major trauma or burns. These effects were closely related with dysfunction of various organs in the course of sepsis. Conclusion These data proved that HMGB1 not only acts as a novel "late" inflammatory mediator but is also closely associated with immunosuppression after acute insults. HMGB1 might play an important role in inducing systemic inflammatory response together with host immunological dissonance, resulting in the development of septic complications. Intervention of HMGB1 expression and release presumably provides a potentially effective way to regulate both excessive inflammatory and immune response, thereby as a measure to improve the prognosis of severe sepsis secondary to major trauma.

Toll-样受体4基因单核苷酸多态性与中国汉族患者脓毒症的相关性

Objective To investigate the correlation between Toll-like receptor 4 (TLR4) single nucleotide polymorphism (SNP) and the risk,severity and prognosis of sepsis in Chinese patients of Han nationality.Methods One hundred and three Han nationality patients who developed sepsis after surgery,aged 18-80 years,were enrolled in the sepsis group,and 114 Han nationality patients without sepsis after surgery,aged 18-80 years,were enrolled in the control group.Venous blood samples were taken from the peripheral vein and three SNPs in TLR4 gene,rs10759932,rs11536889 and rs2737190,were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry analysis.Correction for Logistic regression analysis was made to eliminate the effects of sex,age,underlying diseases and operation methods.The correlation between genotypes of SNP and occurrence of sepsis,organ dysfunction,septic shock and death from sepsis was analyzed.The odds ratio (OR) and 95％ confidence interval (Cl) were calculated.Results Compared with the control group,there was a significant difference in genotype frequency ratios of rs10759932 (P ＜ 0.05),but there was no significant difference in genotype frequency ratios of the other two SNPs in sepsis group (P ＞ 0.05).There was correlation between rs10759932 and the occurrence of sepsis,and the variant allele (CT + CC genotypes) of rs10759932 increased the risk of sepsis (OR =1.86,95％ Cl 1.17-2.97,P ＜ 0.05).There was no correlation between the three SNPs and sepsis-related organ dysfunction,septic shock and death from sepsis (P ＞ 0.05).Conclusion There is correlation between the variant allele of TLR4 rs10759932 and the increase in risk of sepsis after surgery in Chinese patients of Han nationality.

Sepsis相关标志物研究进展

Sepsis是一个古老的话题,2000年前希波克拉底就有对Sepsis的认知.随着医学的发展,人们对其理解也在不断更新[1].全世界每年约有3000万患者因Sepsis住院,其中600万死亡,总病死率约20％[2].因此,Sepsis的诊断及治疗一直是重症医学重要研究方向,近年来逐步被人们接受的“拯救脓毒症”(surviving sepsis campaign,SSC)对Sepsis的诊治提出了系统化、标准化的方案,提倡“早”的理念,即早期识别、早期干预,将改善此类患者的预后[3].

重症医学:基础到临床的艰难历程——从Sepsis3.0说起

重症医学是研究任何损伤或疾病导致机体向死亡方向发展过程的特点和规律性并对重症进行治疗的学科.Sepsis和感染性休克是常见的、典型的临床重症.从Sepsis和感染性休克的定义和治疗的变迁,尤其是从诸如炎症反应综合征的定位、抗生素的合理应用和液体复苏的定量管理等方面,可以看出重症医学从基础到临床的艰难历程和不断发展.

多种生物标志物在脓毒症患者中的临床价值

目的:通过联合检测脓毒症患者血浆氨基末端脑钠肽前体(NT-proBNP)、降钙素原、乳酸及胆碱酯酶的质量浓度,研究其对脓毒症患者病情评估及预后判断的临床意义.方法:用前瞻性研究方法,以2015-01-2017-06期间在我院重症监护室住院的120例脓毒症患者为研究对象.其中一般脓毒症组51例,严重脓毒症组40例,脓毒症休克组29例.对3组患者不同时间NT-proBNP、降钙素原、乳酸及胆碱酯酶质量浓度水平变化进行比较分析,并行APACHEⅡ评分.随访严重脓毒症及脓毒症休克组患者28 d生存情况,对存活组(50例)及死亡组(19例)患者的各项指标进行比较,并比较NT-proBNP、降钙素原、乳酸、胆碱酯酶与APACHEⅡ评分的相关性.结果:与脓毒症组患者相比,严重脓毒症组和脓毒症休克组患者在不同时间血浆NT-proBNP、降钙素原、乳酸水平明显提高,而胆碱酯酶明显降低,3组间比较差异均具有统计学意义(P＜0.05);与严重脓毒症组相比,脓毒症休克组患者在不同时间血浆NT-proBNP、降钙素原、乳酸水平明显提高,而胆碱酯酶明显降低,3组间比较差异均具有统计学意义(P＜0.05);与存活组相比,死亡组血浆NT-proBNP、降钙素原、乳酸质量浓度及A-PACHEⅡ评分均明显提高,而胆碱酯酶水平明显降低,差异具有统计学意义(P＜0.05);血浆NT-proBNP、降钙素原、乳酸质量浓度与APACHEⅡ评分呈正相关,胆碱酯酶的质量浓度与APACHEⅡ评分呈负相关.结论:血浆NT-proBNP、降钙素原、乳酸、胆碱酯酶联合检测对于脓毒症患者预后的评估具有重要的临床指导意义.

Sepsis诊疗进展

由感染引起的全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)称为Sepsis.重症sepsis是常见临床危症,据美国有关医院不完全统计,其发生率占住院病人4.6%0以上,死亡率高,国内外医学界极为关注,其I临床和基础研究近几年来进展极快.

In practice of forensic medicine, potential disease can be associated with fatal asphyxia in re-straint position. Research has demonstrated that nitric oxide (NO) and nitric oxide synthase (NOS) are plentifully distributed in skeletal muscle, contributing to the regulation of contractile and relaxation. In the current study, respiratory functions, indices of diaphragmatic biomechanical functions ex vivo, as well as NO levels in serum, the expressions of diaphragmatic inducible NOS (iNOS) mRNA, and the effects of L-NNA on contractility of the diaphragm were observed in sepsis induced by cecal ligation and punc-ture (CLP) under the condition of restraint position. The results showed that in the CLP12-18 h rats, respiratory dysfunctions; indices of diaphragmatic biomechanical functions (Pt, +dT/dtmax, -dT/dtmax, CT, Po, force over the full range of the force-frequency relationship and fatigue resistance ) declined progressive-ly; the NO level in serum, and iNOS mRNA expression in the diaphragm increased progressively; force increased significantly at all stimulation frequencies after L-NNA pre-incubation. Restraint position 1 h in CLP12 h rats resulted in severe respiratory dysfunctions after relative stable respiratory functions, almost all the indices of diaphragmatic biomechanical functions declined further, whereas little change took place in NO level in serum and diaphragmatic iNOS mRNA expression; and the effects of L-NNA were lack of statistical significance compared with those of CLP12 h, but differed from CLP18 h group. These results suggest that restraint position and sepsis act together in a synergistic manner to aggravate the great reduction of diaphragmatic contractility via, at least in part, the negative modulation of NO, which may contribute to the pathogenesis of positional asphyxia.