目的探讨重症监护室(ICU)医务人员采用1小时集束化治疗策略(1 h bundle)救治脓毒症的执行情况,并分析脓毒症/感染性休克患者28 d预后影响因素.方法选择2019年6月-2022年7月新疆医科大学第一附属医院重症监护病房(ICU)、急诊重症监护病房...目的探讨重症监护室(ICU)医务人员采用1小时集束化治疗策略(1 h bundle)救治脓毒症的执行情况,并分析脓毒症/感染性休克患者28 d预后影响因素.方法选择2019年6月-2022年7月新疆医科大学第一附属医院重症监护病房(ICU)、急诊重症监护病房(EICU)、呼吸重症监护病房(RICU)内符合脓毒症3.0定义与诊断标准患者,根据28 d预后情况分为生存组100例与死亡组91例,收集病原菌与感染部位、1 h bundle执行情况和28 d预后结局等资料;分析影响预后的危险因素并绘制受试者工作特征(ROC)曲线,进一步评估不同指标对脓毒症/感染性休克患者的预测价值.结果191例脓毒症/感染性休克患者共培养分离病原菌295株,其中革兰阴性菌212株占71.86%,革兰阳性菌50株占16.95%,真菌32株占10.85%;感染部位以肺部、腹腔和皮肤软组织为主;1 h bundle策略总体达标率为9.95%,两组达标率差异无统计学意义;28 d病死率为47.64%;年龄(AUC=0.620)、脓毒症相关序贯器官衰竭评分(SOFA)(AUC=0.730)、急性生理与慢性健康Ⅱ(APACHEⅡ)评分(AUC=0.662)、6 h乳酸(AUC=0.590)、24 h乳酸(AUC=0.681)是脓毒症/感染性休克患者28 d预后影响因素;ROC曲线结果显示,年龄、SOFA评分、APACHEⅡ评分、6 h乳酸、24 h乳酸对患者预后情况均有一定预测价值(P<0.05).结论本地区ICU内1 hbundle策略达标率不理想,应探寻行之有效策略提高对于循证指南执行率,进而有效降低脓毒症造成的威胁.展开更多
Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflamm...Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.展开更多
目的调查临床医生在治疗脓毒症3.0定义及诊断标准下的重症监护病房(ICU)脓毒症患者时,执行2018年"拯救脓毒症运动"(SSC)更新的1 h集束化治疗(1 h Bundle)的依从性,并分析其对患者预后的影响。方法采用多中心前瞻性观察性队列...目的调查临床医生在治疗脓毒症3.0定义及诊断标准下的重症监护病房(ICU)脓毒症患者时,执行2018年"拯救脓毒症运动"(SSC)更新的1 h集束化治疗(1 h Bundle)的依从性,并分析其对患者预后的影响。方法采用多中心前瞻性观察性队列研究,选择2019年1月至2020年12月资阳市第一人民医院、资阳市人民医院、雁江区人民医院收治的符合脓毒症3.0定义及诊断标准的153例ICU患者,其中95例完全执行1 h Bundle的患者为Bundle依从组,58例未完成1 h Bundle的患者为Bundle未依从组。统计3家医院的病原菌分布情况和感染部位,以及1 h Bundle依从性执行情况和28 d生存情况。采用单因素分析影响两组脓毒症患者预后的危险因素;采用Cox回归模型绘制28 d生存曲线,评估两组脓毒症患者生存情况。结果3家医院153例脓毒症患者病原菌检出率为61.44%(94/153),以革兰阴性菌为主,占79.79%(75/94);感染部位前3位分别为呼吸系统、胃肠道和泌尿系统,分别占32.0%、28.1%、18.3%。3家医院能完全执行1 h Bundle的患者占62.09%(95/153),1 h Bundle中执行较差的指标为1 h血液微生物培养〔占77.78%(119/153)〕和1 h抗菌药物的应用〔占79.74%(122/153)〕。Bundle是否依从两组患者基线指标比较差异均无统计学意义。单因素分析显示,主要预后指标:Bundle依从组28 d生存率明显高于Bundle未依从组〔80.00%(76/95)比62.06%(36/58),χ^(2)=6.447,P=0.014〕;次要评价指标:Bundle依从组6 h和24 h平均动脉压(MAP)均明显高于Bundle未依从组〔mmHg(1 mmHg=0.133 kPa):78.22±11.25比69.86±14.04,79.78±11.45比75.35±12.90〕,Bundle依从组总住院时间中位数较Bundle未依从组明显延长〔d:13(17)比6(11),P<0.05〕。二元Logistic回归分析显示:6 h和24 h MAP是影响脓毒症患者预后的危险因素〔优势比(OR)和95%可信区间(95%CI)分别为1.064(0.994-1.102)、1.032(1.003-1.063),均P<0.05〕。结论资阳市3家医院ICU脓毒症患者1 h Bundle依从率为62.09%,依从性仍有待提高,特别是经验性抗菌药物使用和抗菌药物使用前留取微生物培养两项的依从性较差。Bundle依从组28 d生存率明显高于Bundle未依从组,说明1 h Bundle方案有助于改善脓毒症患者预后。展开更多
基金supported by the National Natural Science Foundation (81601728,31500726)the Natural Science Foundation of Hunan Province (2021JJ41002),China。
文摘Objective:Inflammation in the central nervous system plays a crucial role in the occurrence and development of sepsis-associated encephalopathy.This study aims to explore the effects of maresin 1(MaR1),an anti-inflammatory and pro-resolving lipid mediator,on sepsis-induced neuroinflammation and cognitive impairment.Methods:Mice were randomly assigned to 4 groups:A sham group(sham operation+vehicle),a cecal ligation and puncture(CLP)group(CLP operation+vehicle),a MaR1-LD group(CLP operation+1 ng MaR1),and a MaR1-HD group(CLP operation+10 ng MaR1).MaR1 or vehicle was intraperitoneally administered starting 1 h before CLP operation,then every other day for 7 days.Survival rates were monitored,and serum inflammatory cytokines[tumor necrosis factor alpha(TNF-α),interleukin(IL)-1β,and IL-6]were measured 24 h after operation using enzyme-linked immunosorbent assay(ELISA).Cognitive function was assessed 7 days after operation using the Morris water maze(MWM)test and novel object recognition(NOR)task.The mRNA expression of TNF-α,IL-1β,IL-6,inducible nitric oxide synthase(iNOS),IL-4,IL-10,and arginase 1(Arg1)in cortical and hippocampal tissues was determined by real-time reverse transcription PCR(RT-PCR).Western blotting was used to determine the protein expression of iNOS,Arg1,signal transducer and activator of transcription 6(STAT6),peroxisome proliferator-activated receptor gamma(PPARγ),and phosphorylated STAT6(p-STAT6)in hippocampal tissue.Microglia activation was visualized via immunofluorescence.Mice were also treated with the PPARγantagonist GW9662 to confirm the involvement of this pathway in MaR1’s effects.Results:CLP increased serum levels of TNF-α,IL-1β,and IL-6,and reduced body weight and survival rates(all P<0.05).Both 1 ng and 10 ng doses of MaR1 significantly reduced serum TNF-α,IL-1β,and IL-6 levels,improved body weight,and increased survival rates(all P<0.05).No significant difference in efficacy was observed between the 2 doses(all P>0.05).MWM test and NOR task indicated that CLP impaired spatial learning,which MaR1 mitigated.However,GW9662 partially reversed MaR1’s protective effects.Real-time RTPCR results demonstrated that,compared to the sham group,mRNA expression of TNF-α,IL-1β,and iNOS significantly increased in hippocampal tissues following CLP(all P<0.05),while IL-4,IL-10,and Arg1 showed a slight decrease,though the differences were not statistically significant(all P>0.05).Compared to the CLP group,both 1 ng and 10 ng MaR1 decreased TNF-α,IL-1β,and iNOS mRNA expression in hippocampal tissues and increased IL-4,IL-10,and Arg1 mRNA expression(all P<0.05).Immunofluorescence results indicated a significant increase in Iba1-positive microglia in the hippocampus after CLP compared to the sham group(P<0.05).Administration of 1 ng and 10 ng MaR1 reduced the percentage area of Iba1-positive cells in the hippocampus compared to the CLP group(both P<0.05).Western blotting results showed that,compared to the CLP group,both 1 ng and 10 ng MaR1 down-regulated the iNOS expression,while up-regulated the expression of Arg1,PPARγ,and p-STAT6(all P<0.05).However,the inclusion of GW9662 counteracted the MaR1-induced upregulation of Arg1 and PPARγcompared to the MaR1-LD group(all P<0.05).Conclusion:MaR1 inhibits the classical activation of hippocampal microglia,promotes alternative activation,reduces sepsis-induced neuroinflammation,and improves cognitive decline.
文摘目的调查临床医生在治疗脓毒症3.0定义及诊断标准下的重症监护病房(ICU)脓毒症患者时,执行2018年"拯救脓毒症运动"(SSC)更新的1 h集束化治疗(1 h Bundle)的依从性,并分析其对患者预后的影响。方法采用多中心前瞻性观察性队列研究,选择2019年1月至2020年12月资阳市第一人民医院、资阳市人民医院、雁江区人民医院收治的符合脓毒症3.0定义及诊断标准的153例ICU患者,其中95例完全执行1 h Bundle的患者为Bundle依从组,58例未完成1 h Bundle的患者为Bundle未依从组。统计3家医院的病原菌分布情况和感染部位,以及1 h Bundle依从性执行情况和28 d生存情况。采用单因素分析影响两组脓毒症患者预后的危险因素;采用Cox回归模型绘制28 d生存曲线,评估两组脓毒症患者生存情况。结果3家医院153例脓毒症患者病原菌检出率为61.44%(94/153),以革兰阴性菌为主,占79.79%(75/94);感染部位前3位分别为呼吸系统、胃肠道和泌尿系统,分别占32.0%、28.1%、18.3%。3家医院能完全执行1 h Bundle的患者占62.09%(95/153),1 h Bundle中执行较差的指标为1 h血液微生物培养〔占77.78%(119/153)〕和1 h抗菌药物的应用〔占79.74%(122/153)〕。Bundle是否依从两组患者基线指标比较差异均无统计学意义。单因素分析显示,主要预后指标:Bundle依从组28 d生存率明显高于Bundle未依从组〔80.00%(76/95)比62.06%(36/58),χ^(2)=6.447,P=0.014〕;次要评价指标:Bundle依从组6 h和24 h平均动脉压(MAP)均明显高于Bundle未依从组〔mmHg(1 mmHg=0.133 kPa):78.22±11.25比69.86±14.04,79.78±11.45比75.35±12.90〕,Bundle依从组总住院时间中位数较Bundle未依从组明显延长〔d:13(17)比6(11),P<0.05〕。二元Logistic回归分析显示:6 h和24 h MAP是影响脓毒症患者预后的危险因素〔优势比(OR)和95%可信区间(95%CI)分别为1.064(0.994-1.102)、1.032(1.003-1.063),均P<0.05〕。结论资阳市3家医院ICU脓毒症患者1 h Bundle依从率为62.09%,依从性仍有待提高,特别是经验性抗菌药物使用和抗菌药物使用前留取微生物培养两项的依从性较差。Bundle依从组28 d生存率明显高于Bundle未依从组,说明1 h Bundle方案有助于改善脓毒症患者预后。
