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
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
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: 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 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
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
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
BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-cente...BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-center study collected data from patients meeting the clinical criteria for systemic inflammatory response syndrome(SIRS) with a confirmed infection source.Patients with coagulation disorders or on medications affecting coagulation were excluded.Patients were divided into sepsis and non-sepsis groups based on a Sequential Organ Failure Assessment(SOFA) score of ≥2.Univariate and multivariate logistic regression identified indicators from routine coagulation tests that predict sepsis.Prognostic roles of coagulation indicators were analyzed within the sepsis group.RESULTS:A total of 512 patients were included,with 396 in the sepsis group and 116 in the non-sepsis group.The predictive factors in the sepsis prediction model encompass fibrin degradation products(FDP),D-dimer,lactate,procalcitonin(PCT) levels and the utilization of mechanical ventilation.Early elevation of FDP and D-dimer levels predicted sepsis onset.The model exhibited an area under the curve(AUC) of 0.943(95% CI:0.923–0.963).In the sepsis group,Cox regression analysis revealed an association between prothrombin time(PT) and in-hospital mortality.CONCLUSION:Abnormal high FDP and D-dimer levels in the early stages of sepsis provide a supplementary method for predicting sepsis.As the disease progresses,prolonged PT in the early stages of sepsis suggests a poor prognosis.展开更多
Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to...Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to other serious complications,which ultimately leads to organ dysfunction and endangers the patient’s life[1].So far,sepsis remains a world public health problem,and according to an analysis of global sepsis data in 2020[2],the number of sepsis cases has increased significantly,with approximately 45 million new cases and 11 million deaths in 2017.According to statistics published in 2021,sepsis accounts for 20%of global deaths[3].Personalised clinical treatment options now available for sepsis include targeted antibiotics and combination therapy,vasopressor therapy,fluid resuscitation,immunomodulatory approaches,and organ-supportive therapy[4].These personalised therapeutic strategies are essential to reduce the complications associated with sepsis.In addition,extracellular vesicles have been found to play an important role in sepsis as a novel biomarker of pathology and diagnosis[5].Therefore,we believe that with the development of medicine,the understanding of sepsis will become more in-depth and comprehensive,and the protracted war with sepsis will certainly achieve new breakthroughs.展开更多
Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the bod...Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].展开更多
BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing int...BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.展开更多
Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of ...Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.展开更多
BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognos...BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.展开更多
Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacter...Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.展开更多
BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the dia...BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the diagnostic accuracy of commonly employed sepsis screening tools and biomarkers remains sparse.We hypothesized that these tools and biomarkers measured at fever onset could distinguish infectious from non-infectious causes of nFUO in critically ill adults.AIM To evaluate the diagnostic utility of sepsis tools and biomarkers in identifying infectious causes of nFUO.METHODS This prospective observational study included patients admitted to the Acute Care Emergency Medicine Unit,Postgraduate Institute of Medical Education and Research,Chandigarh,India(July 2023 to December 2024).nFUO was defined by Durack and Street criteria.Diagnostic performance of sepsis screening tools(systemic inflammatory response syndrome,Sequential Organ Failure Assessment,quick Sequential Organ Failure Assessment,National Early Warning Score,and Modified Early Warning Score)and biomarkers[procalcitonin(PCT),C-reactive protein(CRP)]at fever onset was assessed using receiver operating characteristic curve analysis.RESULTS Of 80 cases(mean age 42.9±16.5 years;80% male),42.5% had infectious causes,38.7% non-infectious,and 18.8% remained undiagnosed.Pneumonia(26.2%)and bloodstream infections(11.2%)were the most common infectious etiologies,while central fever and thrombophlebitis(each 7.5%)were predominant among non-infectious causes.Sepsis tools showed poor diagnostic accuracy,with area under the receiver operating characteristic curve(AUC)values close to 0.5.PCT demonstrated modest performance(AUC=0.61;optimal cut-off:0.85μg/L),while CRP was paradoxically higher in non-infectious cases(AUC=0.45).Overall mortality was 20% and was highest among undiagnosed patients(33.3%).Fever duration and hospitalization length were significantly greater in infectious cases.CONCLUSION Sepsis tools,PCT,and CRP have limited utility in identifying infectious causes of nFUO in critically ill adults and should not solely guide initial decision-making.展开更多
BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Alt...BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Although blood culture is the gold standard for diagnosis,it is not always positive.AIM To evaluate the diagnostic and prognostic utility of D-dimer and heparin-binding protein(HBP)in neonatal sepsis.METHODS This prospective case-control study included 90 neonates in two groups:A sepsis group(n=45)and a control group(n=45)without sepsis.Sepsis group was further subdivided based on blood culture results into proven sepsis(n=28 culturepositive sepsis)and suspected sepsis(n=17 culture-negative sepsis).All neonates underwent complete history taking,thorough clinical examination and investigations[complete blood count,C-reactive protein(CRP),liver and kidney function tests,plasma D-dimer and HBP].RESULTS Levels of CRP,D-dimer and HBP were significantly higher in the sepsis group compared to the controls.At a cutoff value above 517.9 ng/mL,D-dimer outperformed CRP and HBP in distinguishing sepsis group from controls with 95.6%sensitivity and 97.8%specificity.D-dimer was also a better prognostic marker than the neonatal sequential organ failure assessment(nSOFA)for predicting mortality,with 100%sensitivity and 92.5%specificity vs 80%sensitivity and 82.5%specificity.There was a significant positive correlation between CRP,D-dimer and HBP.CONCLUSION D-dimer demonstrated superior diagnostic accuracy compared to CRP and HBP in predicting sepsis,and demonstrated superior prognostic accuracy compared to nSOFA in predicting the outcome of neonatal sepsis.展开更多
Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin fai...Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.展开更多
Objective:To explore the current status of sepsis-associated acute kidney injury(SA-AKI)research and predict its future research directions.Methods:The bibliometric overview of publications was conducted in the field ...Objective:To explore the current status of sepsis-associated acute kidney injury(SA-AKI)research and predict its future research directions.Methods:The bibliometric overview of publications was conducted in the field of SA-AKI based on Web of Science Core Collection database from January 2013 to August 2023.This study employed software such as CiteSpace and VOSviewer to conduct bibliometric and visualization analysis of the included literature,including publication trends,geographic distribution characteristics,author contributions,citations,funding sources characteristics,and keyword clustering.Results:A total of 6509 articles were analyzed,and the number of publications and citations increased from 2013 to 2022.The United States had the highest number of publications in SA-AKI,while France was the country with the highest number of citations per publication.Keyword clustering analysis showed that the pathophysiology and definition of SA-AKI were the research focus,and the research hotspots were"machine learning","vitamin C","kinase","hemodynamics","renal microcirculation"and"mitochondria".Literature coupling analysis indicated that exploring the management and treatment of SA-AKI was the research frontier.Conclusions:Over the past decade,SA-AKI research has shown a upward trend in terms of the number of publication.Research primarily focuses on exploring mechanisms and improving early warning systems.Mechanisms involve microcirculatory dysfunction,inflammation,and other pathophysiological factors.Future recommendations include continuing basic research,achieving clinical application of novel biomarkers,and prioritizing renal recovery mechanisms in treatment strategies.展开更多
BACKGROUND Acute liver failure(ALF)with sepsis is associated with rapid disease progression and high mortality.Therefore,early detection of high-risk sepsis subgroups in patients with ALF is crucial.AIM To develop and...BACKGROUND Acute liver failure(ALF)with sepsis is associated with rapid disease progression and high mortality.Therefore,early detection of high-risk sepsis subgroups in patients with ALF is crucial.AIM To develop and validate an accurate nomogram model for predicting the risk of sepsis in patients with ALF.METHODS We retrieved data from the Medical Information Mart for Intensive Care(MIMIC)IV database and the Fifth Medical Center of Chinese PLA General Hospital(FMCPH).Univariate and multivariate logistic regression analysis were used to identify risk factors for sepsis in ALF and were subsequently incorporated to construct a nomogram model[sepsis in ALF(SIALF)].The discrimination ability,calibration,and clinical applicability of the SIALF model were evaluated by the area under receiver operating characteristic curve,calibration curves,and decision curve analysis,respectively.The Kaplan-Meier curves were used for robustness check.The SIALF model was internally validated using the bootstrapping method with the MIMIC validation cohort and externally validated by the FMCPH cohort.RESULTS A total of 738 patients with ALF patients were included in this study,with 510 from the MIMIC IV database and 228 from the FMCPH cohort.In the MIMIC IV cohort,387(75.89%)patients developed sepsis.Multivariate logistic regression analysis revealed that age[odds ratio(OR)=1.016,95%confidence interval(CI):1.003-1.028,P=0.017],total bilirubin(OR=1.047,95%CI:1.008-1.088,P=0.017),lactate dehydrogenase(OR=1.001,95%CI:1.000-1.001,P<0.001),albumin(OR=0.436,95%CI:0.274-0.692,P=0.003),and mechanical ventilation(OR=1.985,95%CI:1.269-3.105,P=0.003)were independent risk factors associated with sepsis in patients with ALF.The SIALF model demonstrated satisfactory accuracy and clinical utility with area under receiver operating characteristic curve values of 0.849,0.847,and 0.835 for the internal derivation,internal validation,and external validation cohort,respectively,which outperformed the Sequential Organ Failure Assessment scores of 0.733,0.746,and 0.721 and systemic inflammatory response syndrome scores of 0.578,0.653,and 0.615,respectively.The decision curve analysis and calibration curves indicated superior clinical utility and efficiency than other score systems.Based on the risk stratification score derived from the SIALF model,the Kaplan-Meier curves effectively discriminated the real high-risk subpopulation.To enhance the clinical utility,we constructed an online dynamic version,enabling physicians to evaluate patients’condition and track disease progression in real-time.CONCLUSION Based on easily identifiable clinical data,we developed the SIALF model to predict the risk of sepsis in patients with ALF.The model demonstrated robust predictive efficiency,outperformed Sequential Organ Failure Assessment and systemic inflammatory response syndrome scores,and was validated in an external cohort.The model-based risk stratification and online calculator might further facilitate the early detection and appropriate treatment for this subpopulation.展开更多
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.
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.
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.
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.
基金supported by the Science and Technology Commission of Shanghai Municipality (grant no.22Y11900300)China Primary Health Care Foundation (grant no.MTP2022A0132)Project of Shanghai Administration of Traditional Chinese Medicine (ZXXT-202213)to EQM and LM。
文摘BACKGROUND:This study aimed to explore the importance of routine coagulation tests for the early detection of sepsis and to quickly identify patients at a high risk of mortality.METHODS:This retrospective single-center study collected data from patients meeting the clinical criteria for systemic inflammatory response syndrome(SIRS) with a confirmed infection source.Patients with coagulation disorders or on medications affecting coagulation were excluded.Patients were divided into sepsis and non-sepsis groups based on a Sequential Organ Failure Assessment(SOFA) score of ≥2.Univariate and multivariate logistic regression identified indicators from routine coagulation tests that predict sepsis.Prognostic roles of coagulation indicators were analyzed within the sepsis group.RESULTS:A total of 512 patients were included,with 396 in the sepsis group and 116 in the non-sepsis group.The predictive factors in the sepsis prediction model encompass fibrin degradation products(FDP),D-dimer,lactate,procalcitonin(PCT) levels and the utilization of mechanical ventilation.Early elevation of FDP and D-dimer levels predicted sepsis onset.The model exhibited an area under the curve(AUC) of 0.943(95% CI:0.923–0.963).In the sepsis group,Cox regression analysis revealed an association between prothrombin time(PT) and in-hospital mortality.CONCLUSION:Abnormal high FDP and D-dimer levels in the early stages of sepsis provide a supplementary method for predicting sepsis.As the disease progresses,prolonged PT in the early stages of sepsis suggests a poor prognosis.
文摘Introduction Sepsis is a syndrome in which the organism’s response to infection is dysregulated,which is characterised by rapid progression of the disease,and if it is not treated in time,it is very likely to lead to other serious complications,which ultimately leads to organ dysfunction and endangers the patient’s life[1].So far,sepsis remains a world public health problem,and according to an analysis of global sepsis data in 2020[2],the number of sepsis cases has increased significantly,with approximately 45 million new cases and 11 million deaths in 2017.According to statistics published in 2021,sepsis accounts for 20%of global deaths[3].Personalised clinical treatment options now available for sepsis include targeted antibiotics and combination therapy,vasopressor therapy,fluid resuscitation,immunomodulatory approaches,and organ-supportive therapy[4].These personalised therapeutic strategies are essential to reduce the complications associated with sepsis.In addition,extracellular vesicles have been found to play an important role in sepsis as a novel biomarker of pathology and diagnosis[5].Therefore,we believe that with the development of medicine,the understanding of sepsis will become more in-depth and comprehensive,and the protracted war with sepsis will certainly achieve new breakthroughs.
基金supported by the Sichuan Science and Technology Program(2022NSFSC1936)Doctoral Scientific Research Start-up Foundation of China West Normal University(412984).
文摘Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].
基金Supported by the National Natural Science Foundation of China,No.81971814Pudong New Area Health Talent Training Program,No.2025PDWSYCBJ-04Shanghai’s 2023“Technology Innovation Action Plan”Medical Innovation Research Project,No.23Y11908300。
文摘BACKGROUND Intestinal injury is the most common complication of sepsis,and the mitigation of intestinal damage is crucial for treating sepsis.AIM To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.METHODS Through histological analysis,immunohistochemistry,immunofluorescence assays,and Western blot detection,we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis.Additionally,by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples,we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment.This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.RESULTS Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues,enhances the expression of tight junction proteins,and inhibits the polarization of intestinal macrophages,thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice.16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis.Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota.Furthermore,metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group.This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.CONCLUSION Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism,inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.
基金USA National Institutes of Health Grant(R01-HL-139547,to JF)USA VA Grants(1I01BX004838 and IK6BX004211,to JF)+1 种基金National Natural Science Foundation of China(82002087,to TG)Shenzhen Science and Technology Program(JCYJ20210324134602008,to TG)。
文摘Sepsis,a severe systemic inflammatory response to infection,remains a leading cause of morbidity and mortality worldwide.Exosomes,as mediators of intercellular communication,play a pivotal role in the pathogenesis of sepsis through modulating immune responses,metabolic reprogramming,coagulopathy,and organ dysfunction.This review highlights the emerging significance of exosomes in these processes.Initially,it provides an in-depth insight into exosome biogenesis and characterization,laying the groundwork for understanding their diverse and intricate functions.Subsequently,it explores the regulatory roles of exosomes in various immune cells such as neutrophils,macrophages,dendritic cells,T cells,and B cells.This analysis elucidates how exosomes are pivotal in modulating immune responses,thus contributing to the complexity of sepsis pathophysiology.Additionally,this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis.It also establishes a connection between exosomes and the coagulation cascade,which affects endothelial integrity and promotes thrombogenesis in sepsis.Moreover,the review discusses the dual role of exosomes in the progression and resolution of sepsis,exploring their complex involvement in inflammation and healing processes.Furthermore,it underscores their potential as biomarkers and therapeutic targets.Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis,emphasizing the therapeutic promise of exosome research in critical care settings.
基金supported by grants from the municipal Natural Science Foundation of Shanghai Scientific Committee of China(22ZR1451000 to TL)the peak supporting clinical discipline of Shanghai Health Bureau(2023ZDFC0104 to TL)+3 种基金the key clinical discipline of Shanghai Pudong Health Bureau(PWZxk2022-17 to TL)the clinical peak discipline of Shanghai Pudong Heath Bureau(PWYgf2021-03)the top-notch innovative medical talents of Shanghai Pudong Health Bureau(2025PDWSYCBJ-03 to TL)the leading medical talent project of Shanghai Pudong Heath Bureau(PWR12020-07 to LS)。
文摘BACKGROUND:Circulating biomarkers for sepsis are lacking,and research on circular RNAs(circR NAs)as potential biomarkers of pneumonia-induced sepsis is limited.This study aims to investigate the diagnostic and prognostic potential of circRNAs in patients with pneumonia-induced sepsis.METHODS:This prospective cohort study included 40 healthy individuals,60 patients with pneumonia,and 80 patients with pneumonia-induced sepsis.CircRNAs identified through RNA-sequencing were validated using quantitative real-time polymerase chain reaction(qRT-PCR).Spearman correlation analysis was used to evaluate the associations between circRNAs,inflammatory markers,Sequential Organ Failure Assessment(SOFA)scores,and Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)scores.Receiver operating characteristic(ROC)curves analysis were used to assess the diagnostic performance of circRNAs,while ROC curves and Kaplan-Meier survival analysis were used to evaluate their prognostic value of 28-day mortality.RESULTS:qRT-PCR confirmed the significant upregulation of Circ-CTD-2281E23.2 and downregulation of Circ-0075723 and Circ-0008679 in sepsis patients.Spearman correlation analysis showed that Circ-CTD-2281E23.2 was positively correlated with inflammatory markers and severity scores,whereas Circ-0075723 and Circ-0008679 were negatively correlated with these parameters.The area under the curve(AUC)values for Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 in diagnosing pneumonia-induced sepsis were 0.728,0.706,and 0.793,respectively.The combination of these circRNAs(AUC=0.846)and the combination with other clinical indicators(AUC=0.990)demostrated enhanced AUC values.The AUC values for Circ-CTD-2281E23.2 and Circ-0075723 in predicting 28-day mortality were 0.664 and 0.765,respectively.CONCLUSION:This study suggest the additional diagnostic and prognostic value of circRNAs in pneumonia-induced sepsis.Circ-CTD-2281E23.2,Circ-0075723,and Circ-0008679 exhibit diagnostic potential,with Circ-CTD-2281E23.2 and Circ-0075723 showing positive prognostic value for 28-day mortality in sepsis patients.
基金supported by the National Natural Science Foundation of China(82372176,82272217,82002026,81971818)the Hubei Provincial Key Research and Development Program of China(2023BCB091)the National Key Research and Development Program of China(2021YFC2500802,2021YFC2300200).
文摘Sepsis,characterized as life-threatening organ dysfunction resulting from dysregulated host responses to infection,remains a significant challenge in clinical practice.Despite advancements in understanding host-bacterial interactions,molecular responses,and therapeutic approaches,the mortality rate associated with sepsis has consistently ranged between 10%and 16%.This elevated mortality highlights critical gaps in our comprehension of sepsis etiology.Traditionally linked to bacterial and fungal pathogens,recent outbreaks of acute viral infections,including Middle East respiratory syndrome coronavirus(MERS-CoV),influenza virus,and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),among other regional epidemics,have underscored the role of viral pathogenesis in sepsis,particularly when critically ill patients exhibit classic symptoms indicative of sepsis.However,many cases of viral-induced sepsis are frequently underdiagnosed because standard evaluations typically exclude viral panels.Moreover,these viruses not only activate conventional pattern recognition receptors(PRRs)and retinoic acid-inducible gene-I(RIG-I)-like receptors(RLRs)but also initiate primary antiviral pathways such as cyclic guanosine monophosphate adenosine monophosphate(GMP-AMP)synthase(cGAS)-stimulator of interferon genes(STING)signaling and interferon response mechanisms.Such activations lead to cellular stress,metabolic disturbances,and extensive cell damage that exacerbate tissue injury while leading to a spectrum of clinical manifestations.This complexity poses substantial challenges for the clinical management of affected cases.In this review,we elucidate the definition and diagnosis criteria for viral sepsis while synthesizing current knowledge regarding its etiology,epidemiology,and pathophysiology,molecular mechanisms involved therein as well as their impact on immune-mediated organ damage.Additionally,we discuss clinical considerations related to both existing therapies and advanced treatment interventions,aiming to enhance the comprehensive understanding surrounding viral sepsis.
文摘BACKGROUND Nosocomial fever of unknown origin(nFUO)is a frequent and challenging diagnostic entity,encompassing diverse infectious and non-infectious etiologies.Timely identification is crucial,yet evidence on the diagnostic accuracy of commonly employed sepsis screening tools and biomarkers remains sparse.We hypothesized that these tools and biomarkers measured at fever onset could distinguish infectious from non-infectious causes of nFUO in critically ill adults.AIM To evaluate the diagnostic utility of sepsis tools and biomarkers in identifying infectious causes of nFUO.METHODS This prospective observational study included patients admitted to the Acute Care Emergency Medicine Unit,Postgraduate Institute of Medical Education and Research,Chandigarh,India(July 2023 to December 2024).nFUO was defined by Durack and Street criteria.Diagnostic performance of sepsis screening tools(systemic inflammatory response syndrome,Sequential Organ Failure Assessment,quick Sequential Organ Failure Assessment,National Early Warning Score,and Modified Early Warning Score)and biomarkers[procalcitonin(PCT),C-reactive protein(CRP)]at fever onset was assessed using receiver operating characteristic curve analysis.RESULTS Of 80 cases(mean age 42.9±16.5 years;80% male),42.5% had infectious causes,38.7% non-infectious,and 18.8% remained undiagnosed.Pneumonia(26.2%)and bloodstream infections(11.2%)were the most common infectious etiologies,while central fever and thrombophlebitis(each 7.5%)were predominant among non-infectious causes.Sepsis tools showed poor diagnostic accuracy,with area under the receiver operating characteristic curve(AUC)values close to 0.5.PCT demonstrated modest performance(AUC=0.61;optimal cut-off:0.85μg/L),while CRP was paradoxically higher in non-infectious cases(AUC=0.45).Overall mortality was 20% and was highest among undiagnosed patients(33.3%).Fever duration and hospitalization length were significantly greater in infectious cases.CONCLUSION Sepsis tools,PCT,and CRP have limited utility in identifying infectious causes of nFUO in critically ill adults and should not solely guide initial decision-making.
基金Supported by National Liver Institute,Menoufia University,and Damietta General Hospital,Damietta,Egypt.
文摘BACKGROUND Neonatal sepsis is a serious health problem,with high morbidity and mortality during the first 28 days of life.Clinical diagnosis at presentation is challenging due to the nonspecific signs and symptoms.Although blood culture is the gold standard for diagnosis,it is not always positive.AIM To evaluate the diagnostic and prognostic utility of D-dimer and heparin-binding protein(HBP)in neonatal sepsis.METHODS This prospective case-control study included 90 neonates in two groups:A sepsis group(n=45)and a control group(n=45)without sepsis.Sepsis group was further subdivided based on blood culture results into proven sepsis(n=28 culturepositive sepsis)and suspected sepsis(n=17 culture-negative sepsis).All neonates underwent complete history taking,thorough clinical examination and investigations[complete blood count,C-reactive protein(CRP),liver and kidney function tests,plasma D-dimer and HBP].RESULTS Levels of CRP,D-dimer and HBP were significantly higher in the sepsis group compared to the controls.At a cutoff value above 517.9 ng/mL,D-dimer outperformed CRP and HBP in distinguishing sepsis group from controls with 95.6%sensitivity and 97.8%specificity.D-dimer was also a better prognostic marker than the neonatal sequential organ failure assessment(nSOFA)for predicting mortality,with 100%sensitivity and 92.5%specificity vs 80%sensitivity and 82.5%specificity.There was a significant positive correlation between CRP,D-dimer and HBP.CONCLUSION D-dimer demonstrated superior diagnostic accuracy compared to CRP and HBP in predicting sepsis,and demonstrated superior prognostic accuracy compared to nSOFA in predicting the outcome of neonatal sepsis.
文摘Sepsis,a life-threatening condition,can lead to acute skin failure characterized by extensive skin damage.This is often due to decreased blood flow,inflammation,and increased susceptibility to infection.Acute skin failure in people with sepsis is often associated with sleep disturbances,anxiety,and poor mood.Inflammatory markers and lactate levels correlate with these psychiatric symptoms,suggesting a link between skin and brain function.The skin and the central nervous system(CNS)have bidirectional communication.The CNS is also in close contact with the digestive tract.The gut,skin,and brain influence each other’s functions thr-ough nervous,hormonal,and immune pathways,forming a gut-skin-brain axis.Understanding the interaction among the gut,skin,and CNS is critical to the diag-nosis and treatment of various skin and neurological disorders.By recognizing individual variations in gut microbiota,immune responses,and neural pathways,treatments can be tailored to specific patient needs,enhancing efficacy and minimizing side effects.The gut plays a large role in mental health.Under-standing the gut skin brain axis,will lead to improved mental health outcomes.
文摘Objective:To explore the current status of sepsis-associated acute kidney injury(SA-AKI)research and predict its future research directions.Methods:The bibliometric overview of publications was conducted in the field of SA-AKI based on Web of Science Core Collection database from January 2013 to August 2023.This study employed software such as CiteSpace and VOSviewer to conduct bibliometric and visualization analysis of the included literature,including publication trends,geographic distribution characteristics,author contributions,citations,funding sources characteristics,and keyword clustering.Results:A total of 6509 articles were analyzed,and the number of publications and citations increased from 2013 to 2022.The United States had the highest number of publications in SA-AKI,while France was the country with the highest number of citations per publication.Keyword clustering analysis showed that the pathophysiology and definition of SA-AKI were the research focus,and the research hotspots were"machine learning","vitamin C","kinase","hemodynamics","renal microcirculation"and"mitochondria".Literature coupling analysis indicated that exploring the management and treatment of SA-AKI was the research frontier.Conclusions:Over the past decade,SA-AKI research has shown a upward trend in terms of the number of publication.Research primarily focuses on exploring mechanisms and improving early warning systems.Mechanisms involve microcirculatory dysfunction,inflammation,and other pathophysiological factors.Future recommendations include continuing basic research,achieving clinical application of novel biomarkers,and prioritizing renal recovery mechanisms in treatment strategies.
基金Supported by National Key Research and Development Program,No.2022YFA1103501。
文摘BACKGROUND Acute liver failure(ALF)with sepsis is associated with rapid disease progression and high mortality.Therefore,early detection of high-risk sepsis subgroups in patients with ALF is crucial.AIM To develop and validate an accurate nomogram model for predicting the risk of sepsis in patients with ALF.METHODS We retrieved data from the Medical Information Mart for Intensive Care(MIMIC)IV database and the Fifth Medical Center of Chinese PLA General Hospital(FMCPH).Univariate and multivariate logistic regression analysis were used to identify risk factors for sepsis in ALF and were subsequently incorporated to construct a nomogram model[sepsis in ALF(SIALF)].The discrimination ability,calibration,and clinical applicability of the SIALF model were evaluated by the area under receiver operating characteristic curve,calibration curves,and decision curve analysis,respectively.The Kaplan-Meier curves were used for robustness check.The SIALF model was internally validated using the bootstrapping method with the MIMIC validation cohort and externally validated by the FMCPH cohort.RESULTS A total of 738 patients with ALF patients were included in this study,with 510 from the MIMIC IV database and 228 from the FMCPH cohort.In the MIMIC IV cohort,387(75.89%)patients developed sepsis.Multivariate logistic regression analysis revealed that age[odds ratio(OR)=1.016,95%confidence interval(CI):1.003-1.028,P=0.017],total bilirubin(OR=1.047,95%CI:1.008-1.088,P=0.017),lactate dehydrogenase(OR=1.001,95%CI:1.000-1.001,P<0.001),albumin(OR=0.436,95%CI:0.274-0.692,P=0.003),and mechanical ventilation(OR=1.985,95%CI:1.269-3.105,P=0.003)were independent risk factors associated with sepsis in patients with ALF.The SIALF model demonstrated satisfactory accuracy and clinical utility with area under receiver operating characteristic curve values of 0.849,0.847,and 0.835 for the internal derivation,internal validation,and external validation cohort,respectively,which outperformed the Sequential Organ Failure Assessment scores of 0.733,0.746,and 0.721 and systemic inflammatory response syndrome scores of 0.578,0.653,and 0.615,respectively.The decision curve analysis and calibration curves indicated superior clinical utility and efficiency than other score systems.Based on the risk stratification score derived from the SIALF model,the Kaplan-Meier curves effectively discriminated the real high-risk subpopulation.To enhance the clinical utility,we constructed an online dynamic version,enabling physicians to evaluate patients’condition and track disease progression in real-time.CONCLUSION Based on easily identifiable clinical data,we developed the SIALF model to predict the risk of sepsis in patients with ALF.The model demonstrated robust predictive efficiency,outperformed Sequential Organ Failure Assessment and systemic inflammatory response syndrome scores,and was validated in an external cohort.The model-based risk stratification and online calculator might further facilitate the early detection and appropriate treatment for this subpopulation.
