BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify t...BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.展开更多
Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in rece...Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.展开更多
Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to...Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to assess morbidity and mortality of patients with sepsis and to compare the effectiveness of a simple bedside satisfiable Quick Sequential Organ Failure Assessment(qSOFA)score with National Early Warning Score(NEWS)in prognosticating sepsis.Methods:This prospective observational study was conducted among patients>18 years old presenting with sepsis at B.J.Medical College.The SOFA,qSOFA and NEWS scores were calculated.The effectiveness in predicting mortality was evaluated using receiver operating characteristic curve analysis.Results:A total of 200 patients were evaluated(56%male)with a mean age of 51.7 years.The mortality rate was 23%.Patients categorized under high risk according to SOFA score>8,qSOFA score of 2-3 and NEWS>7 had a mortality rate of 33.3%,27.5%and 28.4%,respectively.AUC for mortality prediction was 0.695 using SOFA score,0.665 using qSOFA and 0.725 using NEWS.At a cut off of 7.50,NEWS demonstrated a sensitivity of 97.8%with a specificity of 28.0%and outperformed both SOFA and qSOFA which yielded a sensitivity of 43.5%and 91.3%and a specificity of 77.9%and 27.9%,respectively.Conclusions:The NEWS score outperforms SOFA and qSOFA in predicting mortality among sepsis patients.However,qSOFA is more helpful in identifying high risk patients and performs better in intensive care setting.展开更多
Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategie...Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategies and prognostic assessment.However,trajectory clustering analysis of time-series clinical data poses substantial methodological challenges for researchers.This study provides a comprehensive tutorial framework demonstrating six trajectory modeling approaches integrated with proteomic analysis to guide researchers in identifying sepsis subtypes after laparoscopic surgery.Methods:This study employs simulated longitudinal data from 300 septic patients after laparoscopic surgery to demonstrate six trajectory modeling methods(group-based trajectory modeling,latent growth mixture modeling,latent transition analysis,time-varying effect modeling,K-means for longitudinal data,agglomerative hierarchical clustering)for identifying associations between predefinedsequential organ failure assessment trajectories and 25 proteomic biomarkers.Clustering performance was evaluated via multiple metrics,and a biomarker discovery pipeline integrating principal component analysis,random forests,feature selection,and receiver operating characteristic analysis was developed.Results:The six methods demonstrated varying performance in identifying trajectory structures,with each approach exhibiting distinct analytical characteristics.The performance metrics revealed differences across methods,which may inform context-specificmethod selection and interpretation strategies.Conclusion:This study illustrates practical implementations of trajectory modeling approaches under controlled conditions,facilitating informed method selection for clinical researchers.The inclusion of complete R code and integrated proteomics workflows offers a reproducible analytical framework connecting temporal pattern recognition to biomarker discovery.Beyond sepsis,this pipeline-oriented approach may be adapted to diverse clinical scenarios requiring longitudinal disease characterization and precision medicine applications.The comparative analysis reveals that each method has distinct strengths,providing a practical guide for clinical researchers in selecting appropriate methods based on their specificstudy goals and data characteristics.展开更多
Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LP...Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LPS)-induced septic rat model,revealed the hyperphosphorylation of tau and cognitive impairments,accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats.Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10)as a central regulator of neuroinflammation.LPS triggered CXCL10 secretion in astrocytes,and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits.Recombinant CXCL10 recapitulated these effects in vitro and in vivo.Blocking CXCL10–CXCR3 interaction reversed tau phosphorylation,synaptic impairment,and cognitive decline.Mechanistically,CXCL10–CXCR3 interaction activated CaMKII,driving tau hyperphosphorylation,while CaMKII inhibition restored synaptic protein levels.These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10–CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.展开更多
BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This re...BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.展开更多
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
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
BACKGROUND Aeromonas species are uncommon pathogens in biliary sepsis and cause substantial mortality in patients with impaired hepatobiliary function. Asia has the highest incidence of infection from Aeromonas,wherea...BACKGROUND Aeromonas species are uncommon pathogens in biliary sepsis and cause substantial mortality in patients with impaired hepatobiliary function. Asia has the highest incidence of infection from Aeromonas,whereas cases in the west are rare.CASE SUMMARY We report the case of a 64-year-old woman with advanced pancreatic cancer and jaundice who manifested fever,abdominal pain,severe thrombocytopenia,anemia and kidney failure following the insertion of a percutaneous transhepatic biliary drainage. Blood culture results revealed the presence of Aeromonas veronii biovar veronii(A. veronii biovar veronii). After antibiotic therapy and transfusions,the life-threatening clinical conditions of the patient improved and she was discharged.CONCLUSION This was a rare case of infection,probably the first to be reported in West countries,caused by A. veronii biovar veronii following biliary drainage. A finding of Aeromonas must alert clinician to the possibility of severe sepsis.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: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
BACKGROUND:Large language models(LLMs)are being explored for disease prediction and diagnosis;however,their effi cacy for early sepsis identifi cation in emergency departments(EDs)remains unexplored.This study aims to...BACKGROUND:Large language models(LLMs)are being explored for disease prediction and diagnosis;however,their effi cacy for early sepsis identifi cation in emergency departments(EDs)remains unexplored.This study aims to evaluate MedGo,a novel medical LLM,as a decision-support tool for clinicians managing patients with suspected sepsis.METHODS:This retrospective study included anonymized medical records of 203 patients(mean age 79.9±10.2 years)with confi rmed sepsis from a tertiary hospital ED between January 2023 and January 2024.MedGo performance across nine sepsis-related assessment tasks was compared with that of two junior(<3 years of experience)and two senior(>10 years of experience)ED physicians.Assessments were scored on a 5-point Likert scale for accuracy,comprehensiveness,readability,and case-analysis skills.RESULTS:MedGo demonstrated diagnostic performance comparable to that of senior physicians across most metrics,achieving a median Likert score of 4 in accuracy,comprehensiveness,and readability.MedGo signifi cantly outperformed junior physicians(P<0.001 for accuracy and case-analysis skills).MedGo assistance significantly enhanced both junior(P<0.001)and senior(P<0.05)physicians'diagnostic accuracy.Notably,MedGo-assisted junior physicians achieved accuracy levels comparable to those of unassisted senior physicians.MedGo maintained consistent performance across varying sepsis severities.CONCLUSION:MedGo shows significant diagnostic efficacy for sepsis and effectively supports clinicians in the ED,particularly enhancing junior physicians’performance.Our study highlights the potential of MedGo as a valuable decision-support tool for sepsis management,paving the way for specialized sepsis AI models.展开更多
Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easil...Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easily isolated and cultured for a long time before losing their stem cell characteristics,which are self-renewal and pluripotency.AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics.They are easily accessible,and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells.It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression.These advantages have popularized its use in many fields including plastic reconstructive surgery.However,in the field of hepatology and liver transplantation,the progress is slower.AD-MSC have the potential to modulate inflammation,ameliorate ischemia-reperfusion injury,and support liver and biliary tract regeneration.These are very important for the treatment of various hepatobiliary diseases.Furthermore,the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis.We need alternative therapeutic approaches to treat end-stage liver failure.AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation.Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and 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
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
In order to elucidate the mechanism of liver damage due to acute biliary sepsis,thechanges of hepatocyte mitochondria were observed during biliary sepsis in the rot.Mitochondrial cal-cium content,lysosome fragility of...In order to elucidate the mechanism of liver damage due to acute biliary sepsis,thechanges of hepatocyte mitochondria were observed during biliary sepsis in the rot.Mitochondrial cal-cium content,lysosome fragility of the hepatocytes,lipid peroxide (LPO) level of fiver tissue,omithine carbamyltransferase (OCT),mitochondrial glutamic-oxaloacetic transaminase (m-GOT) andhepatoplastin were determined.It was found that there were overloading of calcium in mitochondria,increase of lysosome fragility,and accumulation of LPO in the liver.These events would result inadverse effects on mitochondrial function The activity of OCT and m-GOT was significantly in-creased,which suggests that mitochondria are seriously damaged since the 2 enzymes mainly comefrom hepatocyte mitochondria.And the liver reserving function declined progressively.Our study indi-cates that mitochondrial damage does exist during acute biliary sepsis,which might playan important role in liver damage.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
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
基金supported by grants from National Natural Science Foundation of China (82402543)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-109)+2 种基金CAMS Innovation Fund for Medical Sciences (CIFMS)(2021-I2M-1-020)Opening Foundation of Agile and Intelligent Computing Key Laboratory of Sichuan ProvinceSpecial Research Fund for Central Universities,Peking Union Medical College (3332024120)
文摘BACKGROUND:Sepsis is a highly heterogeneous organ dysfunction syndrome.There is limited evidence regarding phenotypes and clinical outcomes in sepsis patients with initial normal lactate levels.We sought to identify the lactate-based clinical phenotypes and outcomes of sepsis patients.METHODS:The Medical Information Mart for Intensive Care IV(MIMIC-IV)and eICU databases were used to conduct a retrospective cohort study.Adult sepsis patients were included.Lactate was measured via blood gas,and the same assay type was used across both databases.Serial lactate measurements were analyzed via a two-point classification system based on the highest values recorded during two consecutive 24-hour periods following ICU admission.The fi rst measurement window(T1)comprised the initial 24 h post-admission,whereas the second window(T2)covered 24-48 h post-admission.The lactate diff erence was defi ned as the numerical change between the highest lactate level at T2 and the highest level at T1.The time interval between these two measurements was fi xed,with T2 commencing immediately after T1,together encompassing the fi rst 48 h post-ICU admission.A normal lactate level was defi ned as≤2 mmol/L,and an elevated level was defi ned as>2 mmol/L.Sepsis patients were stratifi ed into four trajectory phenotypes:(1)normal-normal(N-N);(2)normal-elevated(N-E);(3)elevated-normal(E-N);and(4)elevated-elevated(E-E).The primary outcome was in-hospital mortality.RESULTS:This study enrolled 6,926 sepsis patients.The clinical phenotypes of the sepsis patients were as follows:N-N(24.4%),N-E(3.8%),E-N(36.4%),and E-E(35.3%).The in-hospital mortality rates of sepsis patients with the four phenotypes from the MIMIC-IV and eICU databases were as follows(N-N:18.9%vs.17.6%,P=0.66;N-E:35.3%vs.29.2%,P=0.45;E-N:16.6%vs.14.2%,P=0.14;E-E:43.6%vs.37.8%,P=0.01).After adjusting for age,sex,Sequential Organ Failure Assessment(SOFA)score,vasopressor therapy,and infection sites,the N-E phenotype was associated with a higher risk of in-hospital mortality(odds ratio[OR]1.44;95%confidence intervals[95%CI]1.11-1.86;P=0.006;adjusted OR 1.61;95%CI 1.23-2.11;P<0.001).The E-N phenotype was associated with the most favorable outcomes for in-hospital mortality in the multivariable analysis(adjusted OR 0.41;95%CI 0.36-0.46;P<0.001).The E-E phenotype was associated with the highest risk of in-hospital mortality in the overall cohort(adjusted OR 3.00;95%CI 2.67-3.37;P<0.001).CONCLUSION:In sepsis patients with normal initial lactate levels,serial lactate measurements could be valuable for prognostic assessment.
文摘Dysregulated inflammation and multi-organ failure are hallmarks of sepsis,a potentially fatal illness for which there are currently no effective treatments.Fatty acid-binding protein(A-FABP)has been identified in recent research as a crucial mediator of the inflammatory pathways underlying sepsis.In this study,we used a murine model of lipopolysaccharide(LPS)-induced endotoxemia to assess the therapeutic potential of 6H2,a monoclonal antibody that targets A-FABP.In comparison to untreated septic mice,6H2 treatment significantly increased survival rates,decreased histopathological damage in the liver,lungs,kidneys,and heart,and reduced systemic inflammation.According to biochemical analyses,6H2 treatment decreased circulating levels of A-FABP,and this was associated with a reduction in inflammatory markers.These results indicate that A-FABP inhibition is a potentially effective treatment approach for sepsis,with 6H2 demonstrating strong therapeutic efficacy.
文摘Objective:Early sepsis can be treated if recognised early,but progression to severe sepsis and septic shock and multiple organ dysfunction syndrome substantially increases mortality.The objectives of our study were to assess morbidity and mortality of patients with sepsis and to compare the effectiveness of a simple bedside satisfiable Quick Sequential Organ Failure Assessment(qSOFA)score with National Early Warning Score(NEWS)in prognosticating sepsis.Methods:This prospective observational study was conducted among patients>18 years old presenting with sepsis at B.J.Medical College.The SOFA,qSOFA and NEWS scores were calculated.The effectiveness in predicting mortality was evaluated using receiver operating characteristic curve analysis.Results:A total of 200 patients were evaluated(56%male)with a mean age of 51.7 years.The mortality rate was 23%.Patients categorized under high risk according to SOFA score>8,qSOFA score of 2-3 and NEWS>7 had a mortality rate of 33.3%,27.5%and 28.4%,respectively.AUC for mortality prediction was 0.695 using SOFA score,0.665 using qSOFA and 0.725 using NEWS.At a cut off of 7.50,NEWS demonstrated a sensitivity of 97.8%with a specificity of 28.0%and outperformed both SOFA and qSOFA which yielded a sensitivity of 43.5%and 91.3%and a specificity of 77.9%and 27.9%,respectively.Conclusions:The NEWS score outperforms SOFA and qSOFA in predicting mortality among sepsis patients.However,qSOFA is more helpful in identifying high risk patients and performs better in intensive care setting.
基金funding from the China National Key Research and Development Program(No.2023YFC3603104)the National Natural Science Foundation of China(Nos.82472243 and 82272180)+6 种基金the Fundamental Research Funds for the Central Universities(No.226-2025-00024)the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMD24H150001)the Key Research&Development Project of Zhejiang Province(No.2024C03240)a collaborative scientific project co-established by the Science and Technology Department of the National Administration of Traditional Chinese Medicine and the Zhejiang Provincial Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-24082)he General Health Science and Technology Program of Zhejiang Province(No.2024KY1099)the Project of Zhejiang University Longquan Innovation Center(No.ZJDXLQCXZCJBGS2024016)Wu Jieping Medical Foundation Special Research Grant(No.320.6750.2024-23-07).
文摘Objective:Sepsis exhibits remarkable heterogeneity in disease progression trajectories,and accurate identificationof distinct trajectory-based phenotypes is critical for implementing personalized therapeutic strategies and prognostic assessment.However,trajectory clustering analysis of time-series clinical data poses substantial methodological challenges for researchers.This study provides a comprehensive tutorial framework demonstrating six trajectory modeling approaches integrated with proteomic analysis to guide researchers in identifying sepsis subtypes after laparoscopic surgery.Methods:This study employs simulated longitudinal data from 300 septic patients after laparoscopic surgery to demonstrate six trajectory modeling methods(group-based trajectory modeling,latent growth mixture modeling,latent transition analysis,time-varying effect modeling,K-means for longitudinal data,agglomerative hierarchical clustering)for identifying associations between predefinedsequential organ failure assessment trajectories and 25 proteomic biomarkers.Clustering performance was evaluated via multiple metrics,and a biomarker discovery pipeline integrating principal component analysis,random forests,feature selection,and receiver operating characteristic analysis was developed.Results:The six methods demonstrated varying performance in identifying trajectory structures,with each approach exhibiting distinct analytical characteristics.The performance metrics revealed differences across methods,which may inform context-specificmethod selection and interpretation strategies.Conclusion:This study illustrates practical implementations of trajectory modeling approaches under controlled conditions,facilitating informed method selection for clinical researchers.The inclusion of complete R code and integrated proteomics workflows offers a reproducible analytical framework connecting temporal pattern recognition to biomarker discovery.Beyond sepsis,this pipeline-oriented approach may be adapted to diverse clinical scenarios requiring longitudinal disease characterization and precision medicine applications.The comparative analysis reveals that each method has distinct strengths,providing a practical guide for clinical researchers in selecting appropriate methods based on their specificstudy goals and data characteristics.
基金supported by Grants from the National Natural Science Foundation of China(82330041 and 82201326)the China Postdoctoral Research Foundation(GZC20230898)the Science and Technology Innovation Team Project to Xiaochuan Wang from the Department of Science and Technology of Hubei Province(2022-72-18).
文摘Sepsis-associated encephalopathy(SAE)is a severe neurological syndrome marked by widespread brain dysfunctions due to sepsis,yet the underlying mechanisms remain elusive.The current study,using a Lipopolysaccharide(LPS)-induced septic rat model,revealed the hyperphosphorylation of tau and cognitive impairments,accompanied by the release of inflammatory cytokines and activation of glial cells in the hippocampal dentate gyrus region of septic rats.Proteomic and bioinformatic analyses identified C-X-C motif chemokine ligand 10(CXCL10)as a central regulator of neuroinflammation.LPS triggered CXCL10 secretion in astrocytes,and astrocyte-conditioned medium from LPS-treated astrocytes induced tau hyperphosphorylation and synaptic deficits.Recombinant CXCL10 recapitulated these effects in vitro and in vivo.Blocking CXCL10–CXCR3 interaction reversed tau phosphorylation,synaptic impairment,and cognitive decline.Mechanistically,CXCL10–CXCR3 interaction activated CaMKII,driving tau hyperphosphorylation,while CaMKII inhibition restored synaptic protein levels.These findings establish CXCL10 as a key driver of tau pathology in SAE and suggest CXCL10–CXCR3 as a therapeutic target for sepsis-induced cognitive impairments.
文摘BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.
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.
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BACKGROUND Aeromonas species are uncommon pathogens in biliary sepsis and cause substantial mortality in patients with impaired hepatobiliary function. Asia has the highest incidence of infection from Aeromonas,whereas cases in the west are rare.CASE SUMMARY We report the case of a 64-year-old woman with advanced pancreatic cancer and jaundice who manifested fever,abdominal pain,severe thrombocytopenia,anemia and kidney failure following the insertion of a percutaneous transhepatic biliary drainage. Blood culture results revealed the presence of Aeromonas veronii biovar veronii(A. veronii biovar veronii). After antibiotic therapy and transfusions,the life-threatening clinical conditions of the patient improved and she was discharged.CONCLUSION This was a rare case of infection,probably the first to be reported in West countries,caused by A. veronii biovar veronii following biliary drainage. A finding of Aeromonas must alert clinician to the possibility of severe sepsis.
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.
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.
基金supported by grants from the National Natural Science Foundation of China(82470074 to LT)the municipal Natural Science Foundation of Shanghai Scientific Committee of China(22ZR1451000 to LT)+6 种基金the Peak Supporting Clinical Discipline of Shanghai Health Bureau(2023ZDFC0104 to LT)the Medical Discipline Construction Program of Shanghai Pudong New Area Health Commission(the Key Disciplines Program,PWZxk2022-17 to LT)the Scientifi c Research Program of Shanghai Pudong New Area Health Commission(the Joint Research and Development Program,PW2023D-07 to LT)the Healthcare Talents Elite Program of Shanghai Pudong New Area(2025PDWSYCBJ-03 to LT)the Youth Science and Technology Program of Shanghai Pudong New Area(PW2024B-11 to CX)the People’s Livelihood Research Project of Shanghai Pudong Science and Economy Commission(PKJ2023-Y39 to DZ)the Scientifi c Research Program of Shanghai Pudong New Area Health Commission(the Science Popularization Program,PWKP2024B-19 to XL).
文摘BACKGROUND:Large language models(LLMs)are being explored for disease prediction and diagnosis;however,their effi cacy for early sepsis identifi cation in emergency departments(EDs)remains unexplored.This study aims to evaluate MedGo,a novel medical LLM,as a decision-support tool for clinicians managing patients with suspected sepsis.METHODS:This retrospective study included anonymized medical records of 203 patients(mean age 79.9±10.2 years)with confi rmed sepsis from a tertiary hospital ED between January 2023 and January 2024.MedGo performance across nine sepsis-related assessment tasks was compared with that of two junior(<3 years of experience)and two senior(>10 years of experience)ED physicians.Assessments were scored on a 5-point Likert scale for accuracy,comprehensiveness,readability,and case-analysis skills.RESULTS:MedGo demonstrated diagnostic performance comparable to that of senior physicians across most metrics,achieving a median Likert score of 4 in accuracy,comprehensiveness,and readability.MedGo signifi cantly outperformed junior physicians(P<0.001 for accuracy and case-analysis skills).MedGo assistance significantly enhanced both junior(P<0.001)and senior(P<0.05)physicians'diagnostic accuracy.Notably,MedGo-assisted junior physicians achieved accuracy levels comparable to those of unassisted senior physicians.MedGo maintained consistent performance across varying sepsis severities.CONCLUSION:MedGo shows significant diagnostic efficacy for sepsis and effectively supports clinicians in the ED,particularly enhancing junior physicians’performance.Our study highlights the potential of MedGo as a valuable decision-support tool for sepsis management,paving the way for specialized sepsis AI models.
文摘Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easily isolated and cultured for a long time before losing their stem cell characteristics,which are self-renewal and pluripotency.AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics.They are easily accessible,and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells.It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression.These advantages have popularized its use in many fields including plastic reconstructive surgery.However,in the field of hepatology and liver transplantation,the progress is slower.AD-MSC have the potential to modulate inflammation,ameliorate ischemia-reperfusion injury,and support liver and biliary tract regeneration.These are very important for the treatment of various hepatobiliary diseases.Furthermore,the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis.We need alternative therapeutic approaches to treat end-stage liver failure.AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation.Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and 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 National Natural Science Foundation of China,No.38870770
文摘In order to elucidate the mechanism of liver damage due to acute biliary sepsis,thechanges of hepatocyte mitochondria were observed during biliary sepsis in the rot.Mitochondrial cal-cium content,lysosome fragility of the hepatocytes,lipid peroxide (LPO) level of fiver tissue,omithine carbamyltransferase (OCT),mitochondrial glutamic-oxaloacetic transaminase (m-GOT) andhepatoplastin were determined.It was found that there were overloading of calcium in mitochondria,increase of lysosome fragility,and accumulation of LPO in the liver.These events would result inadverse effects on mitochondrial function The activity of OCT and m-GOT was significantly in-creased,which suggests that mitochondria are seriously damaged since the 2 enzymes mainly comefrom hepatocyte mitochondria.And the liver reserving function declined progressively.Our study indi-cates that mitochondrial damage does exist during acute biliary sepsis,which might playan important role in liver damage.
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.
