Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We c...BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We conducted a comprehensive systematic search of MEDLINE,EMBASE,the Cochrane Library,Wanfang,and CNKI from database inception through May 2025,without language restrictions.The primary outcome was a composite of myocardial infarction,stroke,congestive heart failure,or cardiovascular death.To evaluate the association between sepsis survivors and cardiovascular outcomes,we calculated cumulative incidence rates and hazard ratios(HRs)with corresponding 95%confi dence intervals(95%CIs).RESULTS:Twenty-fi ve observational studies comprising 7,525,271 participants were included.The pooled cumulative incidence of major cardiovascular events was 9.0%(95%CI:6.1%-11.9%),myocardial infarction 2.4%(95%CI:1.6%-3.1%),stroke 4.9%(95%CI:3.8%-6.1%),and congestive heart failure 8.6%(95%CI:4.6%-12.6%).Compared with non-sepsis controls,sepsis survivors had a signifi cantly higher risk of major cardiovascular events(HR:1.54;95%CI:1.32-1.79),myocardial infarction(HR:1.41;95%CI:1.29-1.54),stroke(HR:1.45;95%CI:1.32-1.60),and congestive heart failure(HR:1.51;95%CI:1.46-1.56).Risk factors associated with increased cardiovascular events in sepsis survivors included age≤45 years,male,hyperlipidemia,and multiple comorbidities.CONCLUSION:Adult sepsis survivors may face significantly increased risks of long-term cardiovascular outcomes.Both common cardiovascular risk factors and sepsis-related pathophysiological changes contribute to this association.展开更多
Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories...Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.展开更多
Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China li...Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.展开更多
Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive...Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.展开更多
Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory resp...Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.展开更多
Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most seve...Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.展开更多
BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune res...BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune responses initially triggered for protection become harmful because of the failure to restore homeostasis, resulting in ongoing hyperinflammation and immunosuppression. METHODS: A literature review was conducted to address bacterial sepsis, describe advances in understanding complex immunological reactions, critically assess diagnostic approaches, and emphasize the importance of studying bacterial bottlenecks in the detection and treatment of sepsis.RESULTS: Diagnosing sepsis via a single laboratory test is not feasible;therefore, multiple key biomarkers are typically monitored, with a focus on trends rather than absolute values. The immediate interpretation of sepsis-associated clinical signs and symptoms, along with the use of specific and sensitive laboratory tests, is crucial for the survival of patients in the early stages. However, long-term mortality associated with sepsis is now recognized, and alongside the progression of this condition, there is an in vivo selection of adapted pathogens.CONCLUSION: Bacterial sepsis remains a significant cause of mortality across all ages and societies. While substantial progress has been made in understanding the immunological mechanisms underlying the inflammatory response, there is growing recognition that the ongoing host-pathogen interactions, including the emergence of adapted virulent strains, shape both the acute and long-term outcomes in sepsis. This underscores the urgent need for novel high-throughput diagnostic methods and a shift toward more pre-emptive, rather than reactive, treatment strategies in sepsis care.展开更多
BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their e...BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are stil inconclusive. This study aimed to evaluate the overal eff ect of probiotics on the prognosis of patients with sepsis.DATA RESOURCES: We searched several sources for published/presented studies, including Pub Med, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register(www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials(RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit(ICU) mortality and other outcomes.RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children.CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.展开更多
BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especia...BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especially due to rising patterns of cannabis use and its emerging pharmacological role in cancer.METHODS By applying relevant International Classification of Diseases,Ninth and Tenth Revision,Clinical Modification codes to the National Inpatient Sample database between 2016-2020,we identified CUD(+)and CUD(-)arms among adult cancer admissions with severe sepsis.Comparing the two cohorts,we examined baseline demographic characteristics,epidemiological trends,major adverse cardiac and cerebrovascular events,respiratory failure,hospital cost,and length of stay.We used the Pearsonχ^(2) d test for categorical variables and the Mann-Whitney U test for continuous,non-normally distributed variables.Multivariable regression analysis was used to control for potential confounders.A P value≤0.05 was considered for statistical significance.RESULTS We identified a total of 743520 cancer patients admitted with severe sepsis,of which 4945 had CUD.Demographically,the CUD(+)cohort was more likely to be younger(median age=58 vs 69,P<0.001),male(67.9%vs 57.2%,P<0.001),black(23.7%vs 14.4%,P<0.001),Medicaid enrollees(35.2%vs 10.7%,P<0.001),in whom higher rates of substance use and depression were observed.CUD(+)patients also exhibited a higher prevalence of chronic pulmonary disease but lower rates of cardiovascular comorbidities.There was no significant difference in major adverse cardiac and cerebrovascular events between CUD(+)and CUD(-)cohorts on multivariable regression analysis.However,the CUD(+)cohort had lower all-cause mortality(adjusted odds ratio=0.83,95%confidence interval:0.7-0.97,P<0.001)and respiratory failure(adjusted odds ratio=0.8,95%confidence interval:0.69-0.92,P=0.002).Both groups had similar median length of stay,though CUD(+)patients were more likely to have higher hospital cost compared to CUD(-)patients(median=94574 dollars vs 86615 dollars,P<0.001).CONCLUSION CUD(+)cancer patients with severe sepsis,who tended to be younger,black,males with higher rates of substance use and depression had paradoxically significantly lower odds of all-cause in-hospital mortality and respiratory failure.Future research should aim to better elucidate the underlying mechanisms for these observations.展开更多
Sepsis is a life-threatening organ dysfunction associated with a robust systemic inflammatory and immune response to infection.Its pathological consequences lead to multiple organ deficits.Klotho was initially introdu...Sepsis is a life-threatening organ dysfunction associated with a robust systemic inflammatory and immune response to infection.Its pathological consequences lead to multiple organ deficits.Klotho was initially introduced as an antiaging molecule.Its deficiency significantly reduces lifespan,and its overexpression protects against organ injury.It reduces oxidative stress and apoptosis and has anti-inflammatory and antifibrotic properties.In this review,we discuss the underlying mechanisms of sepsis-related klotho down-regulation and the protective role of klotho in sepsis.In developing sepsis-induced multiple organ damage,klotho can modulate multiple downstream signals including nuclear factor-kappaβ,mitogen activated protein kinase,and apoptosis.Multiple studies show klotho's protective effects in sepsis through activation of nuclear factor erythroid-related factor 2,Forkhead transcription factor O,and restoration of internal antioxidant activity.The proposed protective action of klotho is a promising therapeutic strategy for managing sepsis and ameliorating its related organ damage.展开更多
Objective:Neonatal sepsis is a critical pathology that particularly affects neonates,especially preterm and low birth weight neonates,with varying incidence according to the onset(early or late)of the disease.Although...Objective:Neonatal sepsis is a critical pathology that particularly affects neonates,especially preterm and low birth weight neonates,with varying incidence according to the onset(early or late)of the disease.Although preterm neonatal mortality related to sepsis is high in Ethiopia and in the study area,limited studies have been conducted on the time-to-death and predictors of mortality among preterm neonates diagnosed with neonatal sepsis.Therefore,this study aimed to determine the time-to-death and predictors of mortality among preterm neonates with neonatal sepsis admitted to government hospitals in Southwest Ethiopia in 2022.Methods:A prospective cohort study was conducted at the Southwest government hospitals between March 2021 and January 30,2022.The data were entered into Epi-data version 4.4.2.1 and exported to Stata version 14 for editing,cleaning,and analysis.The Cox proportional hazards(CPH)model was used to identify the predictors of mortality.Results:In this study,out of 354 preterm neonates diagnosed with neonatal sepsis,121(34.18%)had died with an incidence rate of 59.8%(95%confidence interval[CI]:50-71.5)deaths per 1000 person-day-observations.The median survival time of preterm neonates diagnosed with neonatal sepsis was 15 days.The following factors were the predictors of mortality among preterm neonates diagnosed with neonatal sepsis:(1)the neonate’s mother did not have antenatal care(ANC)follow-up(adjusted hazard ratio[AHR]2.5[95%CI:1.3-4.84]);(2)the neonates had an APGAR score<7(5th-minute activity,pulse,grimace,appearance,and respiration)(AHR 1.5[95%CI:1.29-3.46]);(3)and they had comorbidities such as respiratory distress syndrome(RDS)(AHR 1.50[95%CI:1.13-2.31])and jaundice(AHR 1.89[95%CI:1.26-2.84]).Conclusions:In this study,preterm neonates diagnosed with neonatal sepsis showed a higher incidence of mortality compared with other national and local studies.The median survival time of neonates was 15 days.Born from mothers who did not have ANC follow-up,5th-minute APGAR score<7,and comorbidities such as RDS and jaundice were independent predictors of mortality among preterm neonates diagnosed with neonatal sepsis.Therefore,healthcare providers and other stakeholders should consider prompt and timely diagnosis and therapeutic interventions to preterm neonates with neonatal sepsis.展开更多
BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-cente...BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-center study collected data from patients meeting the clinical criteria for systemic inflammatory response syndrome(SIRS) with a confirmed infection source.Patients with coagulation disorders or on medications affecting coagulation were excluded.Patients were divided into sepsis and non-sepsis groups based on a Sequential Organ Failure Assessment(SOFA) score of ≥2.Univariate and multivariate logistic regression identified indicators from routine coagulation tests that predict sepsis.Prognostic roles of coagulation indicators were analyzed within the sepsis group.RESULTS:A total of 512 patients were included,with 396 in the sepsis group and 116 in the non-sepsis group.The predictive factors in the sepsis prediction model encompass fibrin degradation products(FDP),D-dimer,lactate,procalcitonin(PCT) levels and the utilization of mechanical ventilation.Early elevation of FDP and D-dimer levels predicted sepsis onset.The model exhibited an area under the curve(AUC) of 0.943(95% CI:0.923–0.963).In the sepsis group,Cox regression analysis revealed an association between prothrombin time(PT) and in-hospital mortality.CONCLUSION:Abnormal high FDP and D-dimer levels in the early stages of sepsis provide a supplementary method for predicting sepsis.As the disease progresses,prolonged PT in the early stages of sepsis suggests a poor prognosis.展开更多
Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to...Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to other serious complications,which ultimately leads to organ dysfunction and endangers the patient’s life[1].So far,sepsis remains a world public health problem,and according to an analysis of global sepsis data in 2020[2],the number of sepsis cases has increased significantly,with approximately 45 million new cases and 11 million deaths in 2017.According to statistics published in 2021,sepsis accounts for 20%of global deaths[3].Personalised clinical treatment options now available for sepsis include targeted antibiotics and combination therapy,vasopressor therapy,fluid resuscitation,immunomodulatory approaches,and organ-supportive therapy[4].These personalised therapeutic strategies are essential to reduce the complications associated with sepsis.In addition,extracellular vesicles have been found to play an important role in sepsis as a novel biomarker of pathology and diagnosis[5].Therefore,we believe that with the development of medicine,the understanding of sepsis will become more in-depth and comprehensive,and the protracted war with sepsis will certainly achieve new breakthroughs.展开更多
Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the bod...Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].展开更多
BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing int...BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.展开更多
BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbala...BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbalance during sepsis.Reactive oxygen species(ROS)are known to influence immune cell signaling,and excessive ROS accumulation may contribute to sepsis-associated immune alterations.AIM To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine(NE)or N-acetylcysteine(NAC)modulate ROS levels following inflammatory stimulation in vitro.METHODS PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection.Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry.PBMCs were also stimulated in vitro with lipopolysaccharide(LPS)or hydrogen peroxide(H2O2),with or without co-treatment with NE or NAC.RESULTS ROS levels were significantly elevated in CD3+and CD14+cells from septic patients compared to controls.In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+and CD14+cells,which was attenuated by cotreatment with NE or NAC.CONCLUSION ROS levels are elevated in specific PBMC subsets in sepsis,particularly CD3+T cells and CD14+monocytes.NE and NAC reduced ROS accumulation in vitro,supporting their potential role as redox modulators.These findings warrant further mechanistic investigation into immune redox regulation in sepsis.展开更多
Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of ...Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.展开更多
BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognos...BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.展开更多
Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacter...Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
基金supported by Zhejiang Province Medical and Health Science and Technology Plan Project(2022KY241)Hangzhou Health Science and Technology Plan Project(ZD20230017).
文摘BACKGROUND:Sepsis may increase the risk of long-term cardiovascular outcomes.This study aims to investigate association between sepsis survivorship and cardiovascular outcomes and to identify risk factors.METHODS:We conducted a comprehensive systematic search of MEDLINE,EMBASE,the Cochrane Library,Wanfang,and CNKI from database inception through May 2025,without language restrictions.The primary outcome was a composite of myocardial infarction,stroke,congestive heart failure,or cardiovascular death.To evaluate the association between sepsis survivors and cardiovascular outcomes,we calculated cumulative incidence rates and hazard ratios(HRs)with corresponding 95%confi dence intervals(95%CIs).RESULTS:Twenty-fi ve observational studies comprising 7,525,271 participants were included.The pooled cumulative incidence of major cardiovascular events was 9.0%(95%CI:6.1%-11.9%),myocardial infarction 2.4%(95%CI:1.6%-3.1%),stroke 4.9%(95%CI:3.8%-6.1%),and congestive heart failure 8.6%(95%CI:4.6%-12.6%).Compared with non-sepsis controls,sepsis survivors had a signifi cantly higher risk of major cardiovascular events(HR:1.54;95%CI:1.32-1.79),myocardial infarction(HR:1.41;95%CI:1.29-1.54),stroke(HR:1.45;95%CI:1.32-1.60),and congestive heart failure(HR:1.51;95%CI:1.46-1.56).Risk factors associated with increased cardiovascular events in sepsis survivors included age≤45 years,male,hyperlipidemia,and multiple comorbidities.CONCLUSION:Adult sepsis survivors may face significantly increased risks of long-term cardiovascular outcomes.Both common cardiovascular risk factors and sepsis-related pathophysiological changes contribute to this association.
文摘Diabetic foot attack(DFA)is the most severe presentation of diabetic foot disease,with the patient commonly displaying severe sepsis,which can be limb or life threatening.DFA can be classified into two main categories:Typical and atypical.A typical DFA is secondary to a severe infection in the foot,often initiated by minor breaches in skin integrity that allow pathogens to enter and proliferate.This form often progresses rapidly due to the underlying diabetic pathophysiology of neuropathy,microvascular disease,and hyperglycemia,which facilitate infection spread and tissue necrosis.This form of DFA can present as one of a number of severe infective pathologies including pyomyositis,necrotizing fasciitis,and myonecrosis,all of which can lead to systemic sepsis and multiorgan failure.An atypical DFA,however,is not primarily infection-driven.It can occur secondary to either ischemia or Charcot arthropathy.Management of the typical DFA involves prompt diagnosis,aggressive infection control,and a multidisciplinary approach.Treatment can be guided by the current International Working Group on the Diabetic Foot/Infectious Diseases Society of America guidelines on diabetic foot infections,and the combined British Orthopaedic Foot and Ankle Society-Vascular Society guidelines.This article highlights the importance of early recognition,comprehensive management strategies,and the need for further research to establish standardized protocols and improve clinical outcomes for patients with DFA.
基金supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-062,to BD).
文摘Sepsis management has significantly improved over the past decades,with intensivists playing a pivotal role in its identification and treatment.[1,2]However,resource constraints in large tertiary hospitals in China limit patient admissions,leading to overcrowding in the emergency departments(EDs)with critically ill patients.[3]This highlights the urgent need for enhanced risk stratification and optimized sepsis management in emergency settings.
基金funded by the Shandong Provincial Natural Science Foundation(No.ZR2024MH008)Postdoctoral Innovation Program of Shandong Province(No.SDCX-ZG-202400043)Beijing iGandan Foundation(No.iGandanF-1082022-RGG007).
文摘Objective This study aimed to develop a prediction model to assess the risk of sepsis-induced coagulopathy(SIC)in sepsis patients.Methods We conducted a retrospective study of septic patients admitted to the Intensive Care Units of Shandong Provincial Hospital(Central Campus and East Campus),and Shenxian People’s Hospital from January 2019 to September 2024.We used Kaplan-Meier analysis to assess survival outcomes.LASSO regression identified predictive variables,and logistic regression was employed to analyze risk factors for pre-SIC.A nomogram prediction model was developed via R software and evaluated via receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA).Results Among 309 patients,236 were in the training set,and 73 were in the test set.The pre-SIC group had higher mortality(44.8%vs.21.3%)and disseminated intravascular coagulation(DIC)incidence(56.3%vs.29.1%)than the non-SIC group.LASSO regression identified lactate,coagulation index,creatinine,and SIC scores as predictors of pre-SIC.The nomogram model demonstrated good calibration,with an AUC of 0.766 in the development cohort and 0.776 in the validation cohort.DCA confirmed the model’s clinical utility.Conclusion SIC is associated with increased mortality,with pre-SIC further increasing the risk of death.The nomogram-based prediction model provides a reliable tool for early SIC identification,potentially improving sepsis management and outcomes.
文摘Sepsis is a life-threatening condition caused by a dysregulated response of the body in response to an infection that harms its tissues and organs.Interleukin-6(IL-6)is a significant component of the inflammatory response as part of the pa-thogenesis of sepsis.It aids in the development of Acute lung injury and,subse-quently,multiple organ dysfunction syndrome.This letter probes into the corre-lation between plasma IL-6 levels and the risk of developing acute lung injury and multiple organ dysfunction syndrome in critically ill patients with sepsis.While it shows promising results,limitations like its observational study design,a limited sample size,a single center involvement,single-time-point measurement,and a lack of a control group restrain its cogency.The study is a big step in identifying IL-6 as a biomarker to improve patient care.
文摘Infection is a public health problem and represents a spectrum of disease that can result in sepsis and septic shock.Sepsis is characterized by a dysregulated immune response to infection.Septic shock is the most severe form of sepsis which leads to distributive shock and high mortality rates.There have been significant advances in sepsis management mainly focusing on early identification and therapy.However,complicating matters is the lack of reliable diagnostic tools and the poor specificity and sensitivity of existing scoring tools i.e.,systemic inflammatory response syndrome criteria,sequential organ failure assessment(SOFA),or quick SOFA.These limitations have underscored the modest progress in reducing sepsis-related mortality.This review will focus on novel therapeutics such as oxidative stress targets,cytokine modulation,endothelial cell modulation,etc.,that are being conceptualized for the management of sepsis and septic shock.
基金funded by the Deanship of Scientific Research (DSR) at King Abdulaziz UniversityJeddah+1 种基金Saudi Arabiaunder grant number G-150-248-1443。
文摘BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune responses initially triggered for protection become harmful because of the failure to restore homeostasis, resulting in ongoing hyperinflammation and immunosuppression. METHODS: A literature review was conducted to address bacterial sepsis, describe advances in understanding complex immunological reactions, critically assess diagnostic approaches, and emphasize the importance of studying bacterial bottlenecks in the detection and treatment of sepsis.RESULTS: Diagnosing sepsis via a single laboratory test is not feasible;therefore, multiple key biomarkers are typically monitored, with a focus on trends rather than absolute values. The immediate interpretation of sepsis-associated clinical signs and symptoms, along with the use of specific and sensitive laboratory tests, is crucial for the survival of patients in the early stages. However, long-term mortality associated with sepsis is now recognized, and alongside the progression of this condition, there is an in vivo selection of adapted pathogens.CONCLUSION: Bacterial sepsis remains a significant cause of mortality across all ages and societies. While substantial progress has been made in understanding the immunological mechanisms underlying the inflammatory response, there is growing recognition that the ongoing host-pathogen interactions, including the emergence of adapted virulent strains, shape both the acute and long-term outcomes in sepsis. This underscores the urgent need for novel high-throughput diagnostic methods and a shift toward more pre-emptive, rather than reactive, treatment strategies in sepsis care.
基金supported by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)Chinese Academy of Medical Science Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)。
文摘BACKGROUND: Sepsis, a common acute and critical disease, leads to 11 million deaths annually worldwide. Probiotics are living microorganisms that are beneficial to the host and may benefit sepsis outcomes, but their effects are stil inconclusive. This study aimed to evaluate the overal eff ect of probiotics on the prognosis of patients with sepsis.DATA RESOURCES: We searched several sources for published/presented studies, including Pub Med, EMBASE, Web of Science, the Cochrane Library and the US National Library of Medicine Clinical Trials Register(www.clinicaltrials.gov) updated through July 30, 2023, to identify all relevant randomized controlled trials(RCTs) or observational studies that assessed the effectiveness of probiotics or synbiotics in patients with sepsis and reported mortality. We focused primarily on mortality during the study period and analyzed secondary outcomes, including 28-day mortality, in-intensive care unit(ICU) mortality and other outcomes.RESULTS: Data from 405 patients in five RCTs and 108 patients in one cohort study were included in the analysis. The overall quality of the studies was satisfactory, but clinical heterogeneity existed. All adult studies reported a tendency for probiotics to reduce the mortality of patients with sepsis, and most studies reported a decreasing trend in the incidence of infectious complications, length of ICU stay and duration of antibiotic use. There was only one RCT involving children.CONCLUSION: Probiotics show promise for improving the prognosis of patients with sepsis, including reducing mortality and the incidence of infectious complications, particularly in adult patients. Despite the limited number of studies, especially in children, these findings will be encouraging for clinical practice in the treatment of sepsis and suggest that gut microbiota-targeted therapy may improve the prognosis of patients with sepsis.
文摘BACKGROUND The burden of cannabis use disorder(CUD)in the context of its prevalence and subsequent cardiopulmonary outcomes among cancer patients with severe sepsis is unclear.AIM To address this knowledge gap,especially due to rising patterns of cannabis use and its emerging pharmacological role in cancer.METHODS By applying relevant International Classification of Diseases,Ninth and Tenth Revision,Clinical Modification codes to the National Inpatient Sample database between 2016-2020,we identified CUD(+)and CUD(-)arms among adult cancer admissions with severe sepsis.Comparing the two cohorts,we examined baseline demographic characteristics,epidemiological trends,major adverse cardiac and cerebrovascular events,respiratory failure,hospital cost,and length of stay.We used the Pearsonχ^(2) d test for categorical variables and the Mann-Whitney U test for continuous,non-normally distributed variables.Multivariable regression analysis was used to control for potential confounders.A P value≤0.05 was considered for statistical significance.RESULTS We identified a total of 743520 cancer patients admitted with severe sepsis,of which 4945 had CUD.Demographically,the CUD(+)cohort was more likely to be younger(median age=58 vs 69,P<0.001),male(67.9%vs 57.2%,P<0.001),black(23.7%vs 14.4%,P<0.001),Medicaid enrollees(35.2%vs 10.7%,P<0.001),in whom higher rates of substance use and depression were observed.CUD(+)patients also exhibited a higher prevalence of chronic pulmonary disease but lower rates of cardiovascular comorbidities.There was no significant difference in major adverse cardiac and cerebrovascular events between CUD(+)and CUD(-)cohorts on multivariable regression analysis.However,the CUD(+)cohort had lower all-cause mortality(adjusted odds ratio=0.83,95%confidence interval:0.7-0.97,P<0.001)and respiratory failure(adjusted odds ratio=0.8,95%confidence interval:0.69-0.92,P=0.002).Both groups had similar median length of stay,though CUD(+)patients were more likely to have higher hospital cost compared to CUD(-)patients(median=94574 dollars vs 86615 dollars,P<0.001).CONCLUSION CUD(+)cancer patients with severe sepsis,who tended to be younger,black,males with higher rates of substance use and depression had paradoxically significantly lower odds of all-cause in-hospital mortality and respiratory failure.Future research should aim to better elucidate the underlying mechanisms for these observations.
文摘Sepsis is a life-threatening organ dysfunction associated with a robust systemic inflammatory and immune response to infection.Its pathological consequences lead to multiple organ deficits.Klotho was initially introduced as an antiaging molecule.Its deficiency significantly reduces lifespan,and its overexpression protects against organ injury.It reduces oxidative stress and apoptosis and has anti-inflammatory and antifibrotic properties.In this review,we discuss the underlying mechanisms of sepsis-related klotho down-regulation and the protective role of klotho in sepsis.In developing sepsis-induced multiple organ damage,klotho can modulate multiple downstream signals including nuclear factor-kappaβ,mitogen activated protein kinase,and apoptosis.Multiple studies show klotho's protective effects in sepsis through activation of nuclear factor erythroid-related factor 2,Forkhead transcription factor O,and restoration of internal antioxidant activity.The proposed protective action of klotho is a promising therapeutic strategy for managing sepsis and ameliorating its related organ damage.
文摘Objective:Neonatal sepsis is a critical pathology that particularly affects neonates,especially preterm and low birth weight neonates,with varying incidence according to the onset(early or late)of the disease.Although preterm neonatal mortality related to sepsis is high in Ethiopia and in the study area,limited studies have been conducted on the time-to-death and predictors of mortality among preterm neonates diagnosed with neonatal sepsis.Therefore,this study aimed to determine the time-to-death and predictors of mortality among preterm neonates with neonatal sepsis admitted to government hospitals in Southwest Ethiopia in 2022.Methods:A prospective cohort study was conducted at the Southwest government hospitals between March 2021 and January 30,2022.The data were entered into Epi-data version 4.4.2.1 and exported to Stata version 14 for editing,cleaning,and analysis.The Cox proportional hazards(CPH)model was used to identify the predictors of mortality.Results:In this study,out of 354 preterm neonates diagnosed with neonatal sepsis,121(34.18%)had died with an incidence rate of 59.8%(95%confidence interval[CI]:50-71.5)deaths per 1000 person-day-observations.The median survival time of preterm neonates diagnosed with neonatal sepsis was 15 days.The following factors were the predictors of mortality among preterm neonates diagnosed with neonatal sepsis:(1)the neonate’s mother did not have antenatal care(ANC)follow-up(adjusted hazard ratio[AHR]2.5[95%CI:1.3-4.84]);(2)the neonates had an APGAR score<7(5th-minute activity,pulse,grimace,appearance,and respiration)(AHR 1.5[95%CI:1.29-3.46]);(3)and they had comorbidities such as respiratory distress syndrome(RDS)(AHR 1.50[95%CI:1.13-2.31])and jaundice(AHR 1.89[95%CI:1.26-2.84]).Conclusions:In this study,preterm neonates diagnosed with neonatal sepsis showed a higher incidence of mortality compared with other national and local studies.The median survival time of neonates was 15 days.Born from mothers who did not have ANC follow-up,5th-minute APGAR score<7,and comorbidities such as RDS and jaundice were independent predictors of mortality among preterm neonates diagnosed with neonatal sepsis.Therefore,healthcare providers and other stakeholders should consider prompt and timely diagnosis and therapeutic interventions to preterm neonates with neonatal sepsis.
基金supported by the Science and Technology Commission of Shanghai Municipality (grant no.22Y11900300)China Primary Health Care Foundation (grant no.MTP2022A0132)Project of Shanghai Administration of Traditional Chinese Medicine (ZXXT-202213)to EQM and LM。
文摘BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-center study collected data from patients meeting the clinical criteria for systemic inflammatory response syndrome(SIRS) with a confirmed infection source.Patients with coagulation disorders or on medications affecting coagulation were excluded.Patients were divided into sepsis and non-sepsis groups based on a Sequential Organ Failure Assessment(SOFA) score of ≥2.Univariate and multivariate logistic regression identified indicators from routine coagulation tests that predict sepsis.Prognostic roles of coagulation indicators were analyzed within the sepsis group.RESULTS:A total of 512 patients were included,with 396 in the sepsis group and 116 in the non-sepsis group.The predictive factors in the sepsis prediction model encompass fibrin degradation products(FDP),D-dimer,lactate,procalcitonin(PCT) levels and the utilization of mechanical ventilation.Early elevation of FDP and D-dimer levels predicted sepsis onset.The model exhibited an area under the curve(AUC) of 0.943(95% CI:0.923–0.963).In the sepsis group,Cox regression analysis revealed an association between prothrombin time(PT) and in-hospital mortality.CONCLUSION:Abnormal high FDP and D-dimer levels in the early stages of sepsis provide a supplementary method for predicting sepsis.As the disease progresses,prolonged PT in the early stages of sepsis suggests a poor prognosis.
文摘Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to other serious complications,which ultimately leads to organ dysfunction and endangers the patient’s life[1].So far,sepsis remains a world public health problem,and according to an analysis of global sepsis data in 2020[2],the number of sepsis cases has increased significantly,with approximately 45 million new cases and 11 million deaths in 2017.According to statistics published in 2021,sepsis accounts for 20%of global deaths[3].Personalised clinical treatment options now available for sepsis include targeted antibiotics and combination therapy,vasopressor therapy,fluid resuscitation,immunomodulatory approaches,and organ-supportive therapy[4].These personalised therapeutic strategies are essential to reduce the complications associated with sepsis.In addition,extracellular vesicles have been found to play an important role in sepsis as a novel biomarker of pathology and diagnosis[5].Therefore,we believe that with the development of medicine,the understanding of sepsis will become more in-depth and comprehensive,and the protracted war with sepsis will certainly achieve new breakthroughs.
基金supported by the Sichuan Science and Technology Program(2022NSFSC1936)Doctoral Scientific Research Start-up Foundation of China West Normal University(412984).
文摘Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].
基金Supported by the National Natural Science Foundation of China,No.81971814Pudong New Area Health Talent Training Program,No.2025PDWSYCBJ-04Shanghai’s 2023“Technology Innovation Action Plan”Medical Innovation Research Project,No.23Y11908300。
文摘BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.
文摘BACKGROUND Sepsis is a life-threatening condition caused by a dysregulated host response to infection.Peripheral blood mononuclear cells(PBMCs)are critical mediators of the immune response and may exhibit redox imbalance during sepsis.Reactive oxygen species(ROS)are known to influence immune cell signaling,and excessive ROS accumulation may contribute to sepsis-associated immune alterations.AIM To assess intracellular ROS levels in PBMC subsets from septic patients and determine whether norepinephrine(NE)or N-acetylcysteine(NAC)modulate ROS levels following inflammatory stimulation in vitro.METHODS PBMCs were isolated from Department of Emergency patients meeting SEP-1/SEP-2 sepsis criteria and from healthy controls without signs of infection.Intracellular ROS levels were measured using a total ROS detection assay and analyzed by flow cytometry.PBMCs were also stimulated in vitro with lipopolysaccharide(LPS)or hydrogen peroxide(H2O2),with or without co-treatment with NE or NAC.RESULTS ROS levels were significantly elevated in CD3+and CD14+cells from septic patients compared to controls.In vitro stimulation of control PBMCs with LPS or H2O2 increased ROS in CD3+and CD14+cells,which was attenuated by cotreatment with NE or NAC.CONCLUSION ROS levels are elevated in specific PBMC subsets in sepsis,particularly CD3+T cells and CD14+monocytes.NE and NAC reduced ROS accumulation in vitro,supporting their potential role as redox modulators.These findings warrant further mechanistic investigation into immune redox regulation in sepsis.
基金USA National Institutes of Health Grant(R01-HL-139547,to JF)USA VA Grants(1I01BX004838 and IK6BX004211,to JF)+1 种基金National Natural Science Foundation of China(82002087,to TG)Shenzhen Science and Technology Program(JCYJ20210324134602008,to TG)。
文摘Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.
基金supported by grants from the municipal Natural Science Foundation of Shanghai Scientific Committee of China(22ZR1451000 to TL)the peak supporting clinical discipline of Shanghai Health Bureau(2023ZDFC0104 to TL)+3 种基金the key clinical discipline of Shanghai Pudong Health Bureau(PWZxk2022-17 to TL)the clinical peak discipline of Shanghai Pudong Heath Bureau(PWYgf2021-03)the top-notch innovative medical talents of Shanghai Pudong Health Bureau(2025PDWSYCBJ-03 to TL)the leading medical talent project of Shanghai Pudong Heath Bureau(PWR12020-07 to LS)。
文摘BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.
基金supported by the National Natural Science Foundation of China(82372176,82272217,82002026,81971818)the Hubei Provincial Key Research and Development Program of China(2023BCB091)the National Key Research and Development Program of China(2021YFC2500802,2021YFC2300200).
文摘Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.
