This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addr...This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.展开更多
BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS...BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.展开更多
Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of deat...Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.展开更多
BACKGROUND Despite various therapies to treat sepsis,it is one of the leading causes of mortality in the intensive care unit patients globally.Knowledge about the pathophysiology of sepsis has sparked interest in extr...BACKGROUND Despite various therapies to treat sepsis,it is one of the leading causes of mortality in the intensive care unit patients globally.Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies(ECT)which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.METHODS In this review,an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis.A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.RESULTS Results showed that ECT techniques such as high-volume hemofiltration,coupled plasma adsorption/filtration,resin or polymer adsorbers,and CytoSorb®are emerging as adjunct therapies to improve hemodynamic stability in sepsis.CytoSorb®has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores,lactate levels,total leucocyte count,platelet count,interleukin-IL-6,IL-10,and TNF levels.CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials.In addition to patient-tailored therapies,future research developments with therapies targeting the cellular level of the immune response are expected.展开更多
Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperla...Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.展开更多
Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing ...Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.展开更多
Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic select...Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic selection, dosage and duration. A growing literature suggests serum procalcitonin (PCT) levels may be useful in guiding antibiotic duration and de-escalation. This report sought to evaluate the evidence-based data available from prospective randomized controlled trials (RCT) on the role of PCT in guiding reductions in antibiotic duration in adult sepsis patients. Methods: A comprehensive search of all published prospective RCT(s) on the use of PCT as a tool for guiding antibiotic therapy in adult sepsis patients was conducted using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results:?Four RCT(s) involving 826 adult sepsis patients have evaluated the role of serum PCT levels to guide criteria for cessation of antibiotic therapy based either on specific PCT levels or PCT kinetics. Bouadma?et al.?(N = 621) stopped antibiotics when the PCT concentration was <80% of the peak PCT value, or the absolute PCT concentration was <0.5 μg/L. The PCT arm showed a 2.7-day reduction in antibiotics. Schroeder?et al.?(N = 27) discontinued antibiotics if clinical signs of infection improved and the PCT value decreased to <1 ng/mL or to <35% of the initial value within three days. The PCT arm had a 1.7-day reduction in antibiotics. Hochreiter?et al.?(N = 110) ceased antibiotics when the PCT decreased to <1 ng/mL, or to 25% - 35% of the initial value over three days if the value was >1 ng/mL. The PCT arm showed a 2-day reduction in antibiotics. Finally, Nobre?et al.?(N = 68) stopped antibiotics when PCT levels decreased by 90% or more from the initial value, but not prior to Day 3 (if baseline PCT measured <1 μg/L) or Day 5 (if baseline PCT measured ≥1 μg/L). The PCT arm showed a 4-day reduction in antibiotics. Overall, reduction of PCT levels to 10% - 35% of the initial concentration, to <80% of the peak PCT value, or to an absolute PCT value of <1 μg/L warranted antibiotic discontinuation 1.7 to 4 days earlier. No study reported a significant difference in mortality between the PCT arm and the control arm (p< 0.05). Conclusions: PCT-guided early cessation of antibiotic therapy in adult sepsis patients is associated with a significant decrease in antibiotic days, with no effect on overall mortality. Measurement of serum PCT levels may have a role in antimicrobial stewardship programs aimed at limiting antibiotic therapy duration, decreasing the selective pressure on drug-resistant bacterial strains and reducing hospital costs.展开更多
Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRA...Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.展开更多
The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if t...The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if the publication of these trials has influenced the use of EGDT when caring for patients with severe sepsis and septic shock in the emergency department (ED). In February 2014, we surveyed a sample of board-certified emergency medicine physicians regarding their use of EGDT in the ED. A follow-up survey was sent after the publication of the sepsis trilogy. Data was analyzed using 95% confidence intervals to determine if there was a change in the use of EGDT following the publication of the above trials. Subgroup analyses were also performed with regard to academic affiliation and emergency department volume. Surveys were sent to 308 and 350 physicians in the pre-and post-publication periods, respectively. Overall, ED use of EGDT did not change with publication of the sepsis trilogy, 48.7% (CI 39.3% - 58.2%) before and 50.5% (CI 40.6% - 60.3%) after. Subgroup analysis revealed that academic-affiliated EDs significantly decreased EGDT use following the sepsis trilogy while nonacademic departments significantly increased EGDT use. Use of EGDT was significantly greater in community departments versus academic departments following the publication of the sepsis trilogy. There was no change overall in the use of EGDT protocols when caring for patients with severe sepsis and septic shock, but subgroup analyses revealed that academic departments decreased their use of EGDT while community departments increased use of EGDT. This may be due to varying rates of uptake of the medical literature between academic and community healthcare systems.展开更多
Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased ...Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased substantially during the last decades, attempts to design effective and specific therapiestargeting components of the derailed host response have failed. Therefore, there is a dramatic need for new and mechanistically alternative therapies to treat this syndrome. Based on their immunomodulatory properties, adult mesenchymal stem or stromal cells(MSCs) can be a novel therapeutic tool to treat sepsis. Indeed, MSCs reduce mortality in experimental models of sepsis by modulating the deregulated inflammatory response against bacteria through the regulation of multiple inflammatory networks, the reprogramming of macrophages and neutrophils towards a more antiinflammatory phenotype and the release of antimicrobial peptides. This report will review the current knowledge on the effects of MSC treatment in preclinical experimental small animal models of sepsis.展开更多
BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual...BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual presentation of liver transplantation to show how successive treatment can be an appropriate option in septic patients after liver transplantation. METHOD: We report on a patient with liver transplantation who developed sepsis due to extended spectrum beta-lactamases and AmpC-producing E. aerogenes. RESULTS: A 39-year-old man had a biliary fistula and then was found to have multiple liver abscesses through abdominal ultrasound and an abdominal computed tomography scan, and carbapenem-sensitive E. aerogenes infection was confirmed. The patient was not successfully treated with conservative treatment consisting of intravenous carbapenems, percutaneous transhepatic cholangial drainage, and biliary stent placement by endoscopic retrograde cholangiopancreatography, so a second liver transplantation followed. Carbapenem-resistant E. aerogenes was detected in bile and blood after a five-week course of carbapenem therapy. The patient developed septic shock and multiple organ dysfunction syndrome. CONCLUSIONS: We first report an unusual case of sepsis caused by E. aerogenes after liver transplantation in China. Carbapenem-resistant E. aerogenes finally leads to uncontrolled sepsis with current antibiotics. We hypothesize that the infection developed as a result of biliary fistula and predisposing immunosuppressive agent therapy. Further research is progressing on the aspect of immunomodulation therapy. (Hepatobiliary Pancreat Dis Int 2009; 8: 320-322)展开更多
BACKGROUND High mobility group box 1(HMGB1)has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin(TM)seems to decrease HMGB1 activity.AIM To investigate the role of the thrombomodu...BACKGROUND High mobility group box 1(HMGB1)has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin(TM)seems to decrease HMGB1 activity.AIM To investigate the role of the thrombomodulin/high mobility group box 1(T/H)ratio in patients with sepsis and their association with their clinic,testing the hypothesis that higher ratios are associated with better outcomes.METHODS Twenty patients diagnosed with sepsis or septic shock,according to the 2016 criteria sepsis and septic shock(Sepsis-3),were studied.Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization(D28).The following clinical outcomes were observed:Sequential Organ Failure Assessment(SOFA)score;Need for mechanical pulmonary ventilation;Presence of septic shock;Occurrence of sepsis-induced coagulopathy;Need for renal replacement therapy(RRT);and Death.RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM:76.41±29.21 pg/mL vs 37.41±22.55 pg/mL among those whose SOFA scores were less than 12 points,P=0.003.The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points,P=0.001.The T/H ratio was,on average,three times higher in patients in need of RRT(0.38±0.14 vs 0.11±0.09),P<0.001.CONCLUSION Higher serum levels of TM and,therefore,higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy,while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.展开更多
We set out to overcome barriers previously shown to impede sepsis therapy. Application of a universally standardized therapy model is an ongoing controversy. By taking advantage of the novel and adaptable aspects of a...We set out to overcome barriers previously shown to impede sepsis therapy. Application of a universally standardized therapy model is an ongoing controversy. By taking advantage of the novel and adaptable aspects of a new technology, we predict that the introduction of an electronic health record based sepsis identification tool in the emergency department will aid clinicians in earlier implementation of sepsis directed therapy, namely intravenous fluids and antibiotics. A retrospective cohort study of 3,076 patients with the diagnosis of sepsis was performed. Patient charts were identified for this study who met the criteria of: _〉 18 years old; emergency department evaluation; ICD-9 code of sepsis, severe sepsis, or septic shock. Data was divided into two treatment groups, pre- and post-best practice advisory (BPA) sepsis identification tool. Our primary outcome was time to intravenous fluids and time to antibiotics administration. The secondary outcome of in-patient all-cause mortality was measured. 1,266 patients were treated prior to, and 1,810 treated after, the BPA implementation with a decrease in time to intravenous fluids from 34% to 49.9% of patient receiving treatment in the first 60 min of emergency department arrival (difference of 15.9%; P 〈 0.05). The time to administration of antibiotics in the first 180 min of arrival improved from 40.3% to 56.8% (difference of 16.5%; P 〈 0.05). Secondarily, we found that in-patient mortality improved from 10.5% to 7.5%, pre- and post BPA respectively (difference of 3%; P 〈 0.05). Our study has demonstrated that the implementation of an active electronic health record screen tool that alerts clinicians to the possibility of sepsis may improve the time to initiate fluid blouses and antibiotics, and may lead to improved outcomes.展开更多
背景中医药治疗脓毒症性急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的疗效确切,但大多数已发表的临床试验设计中缺乏标准、统一的结局指标,造成同类研究结果难以合并、对比,无法产生高质量的循证证据指导临床决策。目的分析2017—2022...背景中医药治疗脓毒症性急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的疗效确切,但大多数已发表的临床试验设计中缺乏标准、统一的结局指标,造成同类研究结果难以合并、对比,无法产生高质量的循证证据指导临床决策。目的分析2017—2022年中医药治疗脓毒症性ALI/ARDS临床试验结局指标的使用情况。方法检索中国知网(CNKI)、万方数据知识服务平台、中国生物医学文献服务系统、PubMed、Web of Science、Embase、Cochrane Library数据库中有关脓毒症性ALI或ARDS的随机对照试验,其中干预组措施为中医药联合其他药物或常规治疗方案,对照组不做限制。采用Cochrane研发的ROB.2工具进行文献质量评价并总结结局指标分类情况。结果经筛选后纳入39篇文献,其中文献偏倚风险评估为低风险1篇(2.56%),高风险3篇(7.69%),可能存在风险35篇(89.74%)。5篇(12.82%)文献结局指标报告质量评分≥5分,为结局指标报告完整。共报告106种结局指标,累计使用443次,包括理化检测(55种,51.89%)、中医症状/证候(2种,1.89%)、症状/体征(13种,12.26%)、远期预后(19种,17.92%)、生活质量(7种,6.60%)、安全性事件(8种,7.55%)和经济学评估(2种,1.89%)。使用率>50%的结局指标有4个,分别是氧合指数(82.05%)、急性生理与慢性健康状况评分系统Ⅱ(58.97%)、机械通气时间(51.28%)和白介素6(51.28%)。21篇文献使用有效率和/或中医证候疗效的复合结局指标,包括总有效率12次,中医证候积分8次和中医症状疗效6次。由于各结局指标差异较大,对106种指标进行合并和依次归类,最终总结出3个大类,分别为:整体评价指标(36种,33.96%)、共性指标(36种,33.96%)及不同关注重点指标(34种,32.08%)。结论目前中医药治疗脓毒症性ALI/ARDS临床试验结局指标的选择尚不规范,主要表现为主次结局指标区分不明确、复合结局指标标准不统一、轻视终点指标、缺少随访数据和中医特色指标等。未来应构建脓毒症性ALI/ARDS的中医药核心结局指标集,推动中医药的高质量发展。展开更多
基金Wenzhou Science and Technology Project(Grant No.Y2020536)。
文摘This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(S ZXK046)the National Nature Science Foundation of China(81571869).
文摘BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.
基金supported by the National Natural Science Foundation of China(82222038,82020108021 and 82260372)the Chongqing Special Project for Academicians(cstc2020yszx-jcyjX0004)the Chongqing Outstanding Youth Foundation and Science Foundation for Outstanding Youth of the Army Medical Centre(2019CXJSB004)。
文摘Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.
文摘BACKGROUND Despite various therapies to treat sepsis,it is one of the leading causes of mortality in the intensive care unit patients globally.Knowledge about the pathophysiology of sepsis has sparked interest in extracorporeal therapies(ECT)which are intended to balance the dysregulation of the immune system by removing excessive levels of inflammatory mediators.AIM To review recent data on the use of ECT in sepsis and to assess their effects on various inflammatory and clinical outcomes.METHODS In this review,an extensive English literature search was conducted from the last two decades to identify the use of ECT in sepsis.A total of 68 articles from peer-reviewed and indexed journals were selected excluding publications with only abstracts.RESULTS Results showed that ECT techniques such as high-volume hemofiltration,coupled plasma adsorption/filtration,resin or polymer adsorbers,and CytoSorb®are emerging as adjunct therapies to improve hemodynamic stability in sepsis.CytoSorb®has the most published data in regard to the use in the field of septic shock with reports on improved survival rates and lowered sequential organ failure assessment scores,lactate levels,total leucocyte count,platelet count,interleukin-IL-6,IL-10,and TNF levels.CONCLUSION Clinical acceptance of ECT in sepsis and septic shock is currently still limited due to a lack of large random clinical trials.In addition to patient-tailored therapies,future research developments with therapies targeting the cellular level of the immune response are expected.
基金supported by grants from the National Natural Science Foundation of China(No.81730057,81501698)the National Key Research and Development Program of China(No.2017YFC11003302)the Shenzhen San-ming Project(No.SZSM20162011)
文摘Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.
基金supported by grants from the National Natural Science Foundation of China(81730057,82130062)the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026)+1 种基金the Guangdong Clinical Research Center for Critical Care Medicine(2020B1111170005)the Sun Yat?sen University Clinical Research Program 5010(2019002)。
文摘Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.
文摘Introduction: With rising global antibiotic resistance, stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens have begun to gain acceptance. These programs stress appropriate antibiotic selection, dosage and duration. A growing literature suggests serum procalcitonin (PCT) levels may be useful in guiding antibiotic duration and de-escalation. This report sought to evaluate the evidence-based data available from prospective randomized controlled trials (RCT) on the role of PCT in guiding reductions in antibiotic duration in adult sepsis patients. Methods: A comprehensive search of all published prospective RCT(s) on the use of PCT as a tool for guiding antibiotic therapy in adult sepsis patients was conducted using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results:?Four RCT(s) involving 826 adult sepsis patients have evaluated the role of serum PCT levels to guide criteria for cessation of antibiotic therapy based either on specific PCT levels or PCT kinetics. Bouadma?et al.?(N = 621) stopped antibiotics when the PCT concentration was <80% of the peak PCT value, or the absolute PCT concentration was <0.5 μg/L. The PCT arm showed a 2.7-day reduction in antibiotics. Schroeder?et al.?(N = 27) discontinued antibiotics if clinical signs of infection improved and the PCT value decreased to <1 ng/mL or to <35% of the initial value within three days. The PCT arm had a 1.7-day reduction in antibiotics. Hochreiter?et al.?(N = 110) ceased antibiotics when the PCT decreased to <1 ng/mL, or to 25% - 35% of the initial value over three days if the value was >1 ng/mL. The PCT arm showed a 2-day reduction in antibiotics. Finally, Nobre?et al.?(N = 68) stopped antibiotics when PCT levels decreased by 90% or more from the initial value, but not prior to Day 3 (if baseline PCT measured <1 μg/L) or Day 5 (if baseline PCT measured ≥1 μg/L). The PCT arm showed a 4-day reduction in antibiotics. Overall, reduction of PCT levels to 10% - 35% of the initial concentration, to <80% of the peak PCT value, or to an absolute PCT value of <1 μg/L warranted antibiotic discontinuation 1.7 to 4 days earlier. No study reported a significant difference in mortality between the PCT arm and the control arm (p< 0.05). Conclusions: PCT-guided early cessation of antibiotic therapy in adult sepsis patients is associated with a significant decrease in antibiotic days, with no effect on overall mortality. Measurement of serum PCT levels may have a role in antimicrobial stewardship programs aimed at limiting antibiotic therapy duration, decreasing the selective pressure on drug-resistant bacterial strains and reducing hospital costs.
文摘Objective: To research the effectiveness of ulinastatin in combination with continuous renal replacement therapy in treating sepsis acute kidney injury and its effect on systemic inflammation, immune function and miRAN expression. Methods: The 84 patients who were diagnosed with sepsis complicated by acute kidney injury in our hospital between May 2020 and June 2022 were chosen and randomly assigned to the study group (n = 42) and the control group (n = 42). Ulinastatin in combination with continuous renal replacement therapy was administered to the study group, whereas the control group was administered with continuous renal replacement therapy alone. Both groups’ clinical effects were observed. The levels of blood urea nitrogen (BUN), serum creatinine (SCr), tumor necrosis factor-α (TNF-α), high sensitivity Creactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), IgG, IgA, IgM, expression levels of miR-233 and miR-10a were compared among both the groups, pre-, and post-treatment. Results: The study group’s overall effectiveness rate was higher that is 95.24%, in comparison to the control group’s 78.57%, and this difference was statistically significant (P α, hs-CRP, VCAM-1, and miR-233 and miR-10a expression levels in both the study and control groups were decreased, however, the study group had reduced levels in comparison to the control group, with statistically significant differences (P P Conclusion: Ulinastatin in combination with continuous renal replacement therapy for treating sepsis acute kidney injury exhibits a positive effect and can significantly improve the systemic inflammation and immune function in patients.
文摘The management of sepsis evolved recently with the publication of three large trials (referred to as the sepsis trilogy) investigating the efficacy of early goal-directed therapy (EGDT). Our goal was to determine if the publication of these trials has influenced the use of EGDT when caring for patients with severe sepsis and septic shock in the emergency department (ED). In February 2014, we surveyed a sample of board-certified emergency medicine physicians regarding their use of EGDT in the ED. A follow-up survey was sent after the publication of the sepsis trilogy. Data was analyzed using 95% confidence intervals to determine if there was a change in the use of EGDT following the publication of the above trials. Subgroup analyses were also performed with regard to academic affiliation and emergency department volume. Surveys were sent to 308 and 350 physicians in the pre-and post-publication periods, respectively. Overall, ED use of EGDT did not change with publication of the sepsis trilogy, 48.7% (CI 39.3% - 58.2%) before and 50.5% (CI 40.6% - 60.3%) after. Subgroup analysis revealed that academic-affiliated EDs significantly decreased EGDT use following the sepsis trilogy while nonacademic departments significantly increased EGDT use. Use of EGDT was significantly greater in community departments versus academic departments following the publication of the sepsis trilogy. There was no change overall in the use of EGDT protocols when caring for patients with severe sepsis and septic shock, but subgroup analyses revealed that academic departments decreased their use of EGDT while community departments increased use of EGDT. This may be due to varying rates of uptake of the medical literature between academic and community healthcare systems.
基金Supported by The Ministerio de Economía y Competitividad(MINECO)Comunidad Autónoma de Madrid(CAM)through the Program Madrid Network
文摘Sepsis is a clinical syndrome caused by a deregulated host response to an infection. Sepsis is the most frequent cause of death in hospitalized patients. Although knowledge of the pathogenesis of sepsis has increased substantially during the last decades, attempts to design effective and specific therapiestargeting components of the derailed host response have failed. Therefore, there is a dramatic need for new and mechanistically alternative therapies to treat this syndrome. Based on their immunomodulatory properties, adult mesenchymal stem or stromal cells(MSCs) can be a novel therapeutic tool to treat sepsis. Indeed, MSCs reduce mortality in experimental models of sepsis by modulating the deregulated inflammatory response against bacteria through the regulation of multiple inflammatory networks, the reprogramming of macrophages and neutrophils towards a more antiinflammatory phenotype and the release of antimicrobial peptides. This report will review the current knowledge on the effects of MSC treatment in preclinical experimental small animal models of sepsis.
文摘BACKGROUND: Sepsis due to Enterobacter aerogenes (E. aerogenes) is rare after liver transplantation but is also a serious infection that may cause liver abscess. The purpose of this case report is to relate an unusual presentation of liver transplantation to show how successive treatment can be an appropriate option in septic patients after liver transplantation. METHOD: We report on a patient with liver transplantation who developed sepsis due to extended spectrum beta-lactamases and AmpC-producing E. aerogenes. RESULTS: A 39-year-old man had a biliary fistula and then was found to have multiple liver abscesses through abdominal ultrasound and an abdominal computed tomography scan, and carbapenem-sensitive E. aerogenes infection was confirmed. The patient was not successfully treated with conservative treatment consisting of intravenous carbapenems, percutaneous transhepatic cholangial drainage, and biliary stent placement by endoscopic retrograde cholangiopancreatography, so a second liver transplantation followed. Carbapenem-resistant E. aerogenes was detected in bile and blood after a five-week course of carbapenem therapy. The patient developed septic shock and multiple organ dysfunction syndrome. CONCLUSIONS: We first report an unusual case of sepsis caused by E. aerogenes after liver transplantation in China. Carbapenem-resistant E. aerogenes finally leads to uncontrolled sepsis with current antibiotics. We hypothesize that the infection developed as a result of biliary fistula and predisposing immunosuppressive agent therapy. Further research is progressing on the aspect of immunomodulation therapy. (Hepatobiliary Pancreat Dis Int 2009; 8: 320-322)
文摘BACKGROUND High mobility group box 1(HMGB1)has been studied as a molecule associated with severe outcomes in sepsis and thrombomodulin(TM)seems to decrease HMGB1 activity.AIM To investigate the role of the thrombomodulin/high mobility group box 1(T/H)ratio in patients with sepsis and their association with their clinic,testing the hypothesis that higher ratios are associated with better outcomes.METHODS Twenty patients diagnosed with sepsis or septic shock,according to the 2016 criteria sepsis and septic shock(Sepsis-3),were studied.Patients were followed until they left the intensive care unit or until they achieved 28 d of hospitalization(D28).The following clinical outcomes were observed:Sequential Organ Failure Assessment(SOFA)score;Need for mechanical pulmonary ventilation;Presence of septic shock;Occurrence of sepsis-induced coagulopathy;Need for renal replacement therapy(RRT);and Death.RESULTS The results showed that patients with SOFA scores greater than or equal to 12 points had higher serum levels of TM:76.41±29.21 pg/mL vs 37.41±22.55 pg/mL among those whose SOFA scores were less than 12 points,P=0.003.The T/H ratio was also higher in patients whose SOFA scores were greater than or equal to 12 points,P=0.001.The T/H ratio was,on average,three times higher in patients in need of RRT(0.38±0.14 vs 0.11±0.09),P<0.001.CONCLUSION Higher serum levels of TM and,therefore,higher T/H ratio in the first 24 h after the diagnosis of sepsis were associated with more severe disease and the need for renal replacement therapy,while those with better clinical outcomes and those who were discharged before D28 showed a tendency for lower T/H ratio values.
文摘We set out to overcome barriers previously shown to impede sepsis therapy. Application of a universally standardized therapy model is an ongoing controversy. By taking advantage of the novel and adaptable aspects of a new technology, we predict that the introduction of an electronic health record based sepsis identification tool in the emergency department will aid clinicians in earlier implementation of sepsis directed therapy, namely intravenous fluids and antibiotics. A retrospective cohort study of 3,076 patients with the diagnosis of sepsis was performed. Patient charts were identified for this study who met the criteria of: _〉 18 years old; emergency department evaluation; ICD-9 code of sepsis, severe sepsis, or septic shock. Data was divided into two treatment groups, pre- and post-best practice advisory (BPA) sepsis identification tool. Our primary outcome was time to intravenous fluids and time to antibiotics administration. The secondary outcome of in-patient all-cause mortality was measured. 1,266 patients were treated prior to, and 1,810 treated after, the BPA implementation with a decrease in time to intravenous fluids from 34% to 49.9% of patient receiving treatment in the first 60 min of emergency department arrival (difference of 15.9%; P 〈 0.05). The time to administration of antibiotics in the first 180 min of arrival improved from 40.3% to 56.8% (difference of 16.5%; P 〈 0.05). Secondarily, we found that in-patient mortality improved from 10.5% to 7.5%, pre- and post BPA respectively (difference of 3%; P 〈 0.05). Our study has demonstrated that the implementation of an active electronic health record screen tool that alerts clinicians to the possibility of sepsis may improve the time to initiate fluid blouses and antibiotics, and may lead to improved outcomes.
文摘背景中医药治疗脓毒症性急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的疗效确切,但大多数已发表的临床试验设计中缺乏标准、统一的结局指标,造成同类研究结果难以合并、对比,无法产生高质量的循证证据指导临床决策。目的分析2017—2022年中医药治疗脓毒症性ALI/ARDS临床试验结局指标的使用情况。方法检索中国知网(CNKI)、万方数据知识服务平台、中国生物医学文献服务系统、PubMed、Web of Science、Embase、Cochrane Library数据库中有关脓毒症性ALI或ARDS的随机对照试验,其中干预组措施为中医药联合其他药物或常规治疗方案,对照组不做限制。采用Cochrane研发的ROB.2工具进行文献质量评价并总结结局指标分类情况。结果经筛选后纳入39篇文献,其中文献偏倚风险评估为低风险1篇(2.56%),高风险3篇(7.69%),可能存在风险35篇(89.74%)。5篇(12.82%)文献结局指标报告质量评分≥5分,为结局指标报告完整。共报告106种结局指标,累计使用443次,包括理化检测(55种,51.89%)、中医症状/证候(2种,1.89%)、症状/体征(13种,12.26%)、远期预后(19种,17.92%)、生活质量(7种,6.60%)、安全性事件(8种,7.55%)和经济学评估(2种,1.89%)。使用率>50%的结局指标有4个,分别是氧合指数(82.05%)、急性生理与慢性健康状况评分系统Ⅱ(58.97%)、机械通气时间(51.28%)和白介素6(51.28%)。21篇文献使用有效率和/或中医证候疗效的复合结局指标,包括总有效率12次,中医证候积分8次和中医症状疗效6次。由于各结局指标差异较大,对106种指标进行合并和依次归类,最终总结出3个大类,分别为:整体评价指标(36种,33.96%)、共性指标(36种,33.96%)及不同关注重点指标(34种,32.08%)。结论目前中医药治疗脓毒症性ALI/ARDS临床试验结局指标的选择尚不规范,主要表现为主次结局指标区分不明确、复合结局指标标准不统一、轻视终点指标、缺少随访数据和中医特色指标等。未来应构建脓毒症性ALI/ARDS的中医药核心结局指标集,推动中医药的高质量发展。