In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pha...In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients(APIs)such as solubility,permeability,and bioavailability,all without altering their chemical structure.This approach opens new avenues for developing natural products into effective drugs,especially those previously challenging in formulation.Emodin,an anthraquinone-based natural product,is a notable example due to its diverse biological activities;however,its physicochemical limitations,such as poor solubility and easy sublimation,restricted its clinical application.While various methods have improved emodin's physicochemical properties,research on its bioavailability remains limited.In our study,we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer.Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities.Ultimately,we successfully obtained the emodin-piperazine cocrystal,which were characterized and evaluated by several in vitro methods and pharmacokinetic studies.In addition,experiments have shown that emodin has a certain therapeutic effect on sepsis,so we also evaluated emodin-piperazine biological activity in a sepsis model.The results demonstrate that co-crystallization significantly enhances emodin's solubility,permeability,and bioavailability.Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis.This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.展开更多
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
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
This article reviews the research advances in traditional Chinese medicine rhubarb and its compound formulations in the treatment of sepsis,with particular emphasis on elucidating their mechanisms of action and clinic...This article reviews the research advances in traditional Chinese medicine rhubarb and its compound formulations in the treatment of sepsis,with particular emphasis on elucidating their mechanisms of action and clinical application value.Research has demonstrated that rhubarb and its compound formulations exert therapeutic effects via multiple targets and mechanisms,including anti-inflammatory actions,protection of the intestinal barrier,modulation of immune balance,inhibition of oxidative stress,and regulation of associated signaling pathways.Clinically,rhubarb has shown distinct advantages in enhancing gastrointestinal function,mitigating systemic inflammatory responses,and reducing mortality rates among patients with sepsis.These findings provide a foundational reference for the integrated prevention and treatment of sepsis through the combined use of traditional Chinese and Western medicine.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
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
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
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 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
基金funded by the National Natural Science Foundation of China(No.22278443)CAMS Innovation Fund for Medical Sciences(No.2022-I2M-1-015)+3 种基金the Key R&D Program of Shandong Province(No.2021ZDSYS26)Xinjiang Uygur Autonomous Region Innovation Environment Construction Special Fund and Technology Innovation Base Construction Key Laboratory Open Project(No.2023D04065)2023 Xinjiang Uygur Autonomous Region Innovation Tianchi Talent Introduction Program for financial supportthe Key Project of Natural Science of Bengbu Medical University(No.2024byzd138).
文摘In the pharmaceutical field,machine learning can play an important role in drug development,production and treatment.Co-crystallization techniques have shown promising potential to enhance the properties of active pharmaceutical ingredients(APIs)such as solubility,permeability,and bioavailability,all without altering their chemical structure.This approach opens new avenues for developing natural products into effective drugs,especially those previously challenging in formulation.Emodin,an anthraquinone-based natural product,is a notable example due to its diverse biological activities;however,its physicochemical limitations,such as poor solubility and easy sublimation,restricted its clinical application.While various methods have improved emodin's physicochemical properties,research on its bioavailability remains limited.In our study,we summarize cocrystals and salts produced through co-crystallization technology and identify piperazine as a favorable coformer.Conflicting conclusions from computational chemistry and molecular modeling method and machine learning method regarding the formation of an emodin-piperazine cocrystal or salt led us to experimentally validate these possibilities.Ultimately,we successfully obtained the emodin-piperazine cocrystal,which were characterized and evaluated by several in vitro methods and pharmacokinetic studies.In addition,experiments have shown that emodin has a certain therapeutic effect on sepsis,so we also evaluated emodin-piperazine biological activity in a sepsis model.The results demonstrate that co-crystallization significantly enhances emodin's solubility,permeability,and bioavailability.Pharmacodynamic studies indicate that the emodin-piperazine cocrystal improves sepsis symptoms and provides protective effects against liver and kidney damage associated with sepsis.This study offers renewed hope for natural products with broad biological activities yet hindered by physicochemical limitations by advancing co-crystallization as a viable development approach.
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 National Natural Science Foundation of China(82374346)Double Hundred Outstanding Young and Middle-aged Medical and Health Talents of Wuxi City(BJ2023071)Scientific Research Project of Wuxi Municipal Health Commission(Q202358).
文摘This article reviews the research advances in traditional Chinese medicine rhubarb and its compound formulations in the treatment of sepsis,with particular emphasis on elucidating their mechanisms of action and clinical application value.Research has demonstrated that rhubarb and its compound formulations exert therapeutic effects via multiple targets and mechanisms,including anti-inflammatory actions,protection of the intestinal barrier,modulation of immune balance,inhibition of oxidative stress,and regulation of associated signaling pathways.Clinically,rhubarb has shown distinct advantages in enhancing gastrointestinal function,mitigating systemic inflammatory responses,and reducing mortality rates among patients with sepsis.These findings provide a foundational reference for the integrated prevention and treatment of sepsis through the combined use of traditional Chinese and Western medicine.
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 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.
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.
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].
