Value of procalcitonin and presepsin in the diagnosis and severity stratification of sepsis and septic shock

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1,2]Septic shock,the most severe form of sepsis,is characterized by circulatory and cellular/metabolic abnormalities,and can increase mortality to>40%.[1-3]Early recognition and risk stratification of septic shock are crucial but challenging because of the heterogeneity of its presentation and progression.

Aggressive fluid management may be associated with disease progression in suspected sepsis patients admitted to the intensive care unit: a retrospective cohort study

Sepsis is a lethal condition characterized by multiple organ dysfunction due to disrupted host responses to severe infections.[1]Aff ected patients often have a Sequential Organ Failure Assessment(SOFA)score≥2.[2]Patients with a SOFA score<2 and at least one of the following were considered as“suspected sepsis”:(1)quick SOFA(qSOFA)score≥2;(2)SOFA score=1;or(3)National Early Warning Score(NEWS)4-6.[3]Compared with studies on fluid resuscitation in sepsis patients,there are few studies on fluid management in patients with suspected sepsis.Therefore,we conducted a retrospective cohort study to evaluate the relationship between fluid management and disease progression in suspected sepsis patients.

Characteristics and Risk Factors for Pediatric Sepsis

Objective Sepsis is considered a major cause of health loss in children and had high mortality and morbidity.Currently,there is no reliable model for predicting the prognosis of pediatric patients with sepsis.This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes.Methods This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,China,from January 1,2019,to December 31,2021.Risk factors for sepsis were identified by logistic regression analyses.Results A total of 355 children with sepsis were enrolled,with 333 children(93.8%)in the good prognosis group,and 22 children(6.2%)in the poor prognosis group.Among them,there were 255 patients(71.8%)in the sepsis group,and 100 patients(28.2%)in the severe sepsis group.The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group(P<0.01).The levels of interleukin 1β(IL-1β)in the poor prognosis group were higher than those in the good prognosis group(P>0.05),and the platelet(PLT),albumin(ALB),and hemoglobin(Hb)levels were lower in the poor prognosis group(P<0.01).The IL-8 levels in the severe sepsis group were higher than those in the sepsis group(P<0.05).Multiple logistic regression analysis suggested that lower Hb levels,ALB levels,peak PLT counts,and higher IL-1βlevels were independent risk factors for poor prognosis in children with sepsis.Conclusion Lower Hb,ALB,and PLT counts and elevated IL-1βare independent risk factors for poor prognosis in children with sepsis.

Identification of clinical subphenotypes of sepsis after laparoscopic surgery

Objective:Some patients exhibit septic symptoms following laparoscopic surgery,leading to a poor prognosis.Effective clinical subphenotyping is critical for guiding tailored therapeutic strategies in these cases.By identifying predisposing factors for postoperative sepsis,clinicians can implement targeted interventions,potentially improving outcomes.This study outlines a workflow for the subphenotype methodology in the context of laparoscopic surgery,along with its practical application.Methods:This study utilized data routinely available in clinical case systems,enhancing the applicability of our findings.The data included vital signs,such as respiratory rate,and laboratory measures,such as blood sodium levels.The process of categorizing clinical routine data involved technical complexities.A correlation heatmap was used to visually depict the relationships between variables.Ordering points were used to identify the clustering structure and combined with Consensus K clustering methods to determine the optimal categorization.Results:Our study highlighted the intricacies of identifying clinical subphenotypes following laparoscopic surgery,and could thus serve as a valuable resource for clinicians and researchers seeking to explore disease heterogeneity in clinical settings.By simplifying complex methodologies,we aimed to bridge the gap between technical expertise and clinical application,fostering an environment where professional medical knowledge is effectively utilized in subphenotyping research.Conclusion:This tutorial could primarily serve as a guide for beginners.A variety of clustering approaches were explored,and each step in the process contributed to a comprehensive understanding of clinical subphenotypes.

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Factors Associated with Neonatal Sepsis: A Case Study at Chilenje General Hospital in the Neonatal Unit and Paediatric Wards

Background: Neonatal sepsis is known to result in 26% of mortalities in children below the age of five worldwide, countries in Sub-Saharan African recording the highest deaths. Although the deaths of neonates have reduced world over up to 3.6 million counts, Chilenje General Hospital continues to register significant numbers of neonatal sepsis. This study aimed at investigating the factors associated with neonatal sepsis at Chilenje General Hospital in Lusaka, Zambia. Methods: An institution based cross-sectional study design was conducted at Chilenje General Hospital. Data were collected by the use of a researcher designed questionnaire and analysed using SPSS version 25. Frequencies were used for descriptive analysis while bivariate analysis was used to establish association among risk factors and outcome variables. Variables with significant association at 5% level were further subjected to multivariate analysis at α ≤ 0.05. Results: The study showed that out of 156 neonates, 40.4% (63/156) developed neonatal sepsis. Maternal factors that projected the incidence of sepsis amongst neonates were distance to nearest health facility [AOR: 6.3 (95% CI: 1.8 - 21.3), p = 0.003], occupation [AOR: 5.8 (95% CI: 1.2 - 27.6), p = 0.026], number of antenatal visits [AOR: 6.3 (95% CI: 1.9 - 21.6), p = 0.003], number of vaginal examinations [AOR: 10.8 (95% CI: 2.8 - 42), p = 0.001], and pregnancy induced hypertension [AOR: 5.4 (95% CI: 1.4 - 20), p = 0.013]. Neonatal risk factor which projected the incidence of sepsis was Neonate’s age [AOR: 18.8 (95% CI: 4.9 - 72.5), p = 0.000]. Conclusions: The chance of developing neonatal sepsis was strongly correlated with both mother and child variables, according to the study. In order to lower the chance of the neonate acquiring sepsis, encouraging maternal antenatal care use would assist to detect risk factors during prenatal, perinatal and postnatal care and apply the proper therapies.

Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis

BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.

Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong Kong.The primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED presentation.Using c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time points.RESULTS:We analyzed 601 patients,of whom 166(27.6%)developed sepsis.NEWS2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary outcome.However,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),respectively.The discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time point.CONCLUSION:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

Knowledge,management,and complications of sepsis and septic shock:A significant therapeutic challenge in the intensive care unit

Sepsis and septic shock are life-threatening conditions that are globally responsible for almost 20%of mortality,especially in low and middle-income countries.This review was conducted on PubMed and Google Scholar databases with keywords sepsis,septic shock,sepsis management,and sepsis complications.Articles published up to July 2023 in English were included.Diagnosis and management should be carried out without unnecessary delay.Cooperation between various medical specialties including intensive care doctors,neurologists,hepatologists,cardiologists,and pediatric doctors is needed if a child is affected.New strategies have to be implemented in low and middle-income countries to decrease the sepsis incidence and reduce mortality in the population.

Traditional Chinese medicine Pien-Tze-Huang ameliorates LPS-induced sepsis through bile acid-mediated activation of TGR5-STAT3-A20 signalling

Pien Tze Huang(PZH),a class-1 nationally protected traditional Chinese medicine(TCM),has been used to treat liver diseases such as hepatitis;however,the effect of PZH on the progression of sepsis is unknown.Here,we reported that PZH attenuated lipopolysaccharide(LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase(MAPK)and nuclear factor-kappa B(NF-κB)signalling.Mechanistically,PZH stimulated signal transducer and activator of transcription 3(STAT3)phosphorylation to induce the expression of A20,which could inhibit the activation of NF-κB and MAPK signalling.Knockdown of the bile acid(BA)receptor G protein-coupled bile acid receptor 1(TGR5)in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction,as well as the LPS-induced inflammatory response,suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5.Consistently,deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20,the activation of NF-κB and MAPK signalling,and the production of proinflammatory cytokines,whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines.Overall,our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

A Comparison between Late Preterm and Term Infants with Respiratory Distress Syndrome, Early-Onset Sepsis, and Neonatal Jaundice in Ecuadorian Newborns

Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.

Sepsis one-hour bundle management combined with psychological intervention on negative emotion and sleep quality in patients with sepsis

BACKGROUND Sepsis is a serious infectious disease caused by various systemic inflammatory responses and is ultimately life-threatening.Patients usually experience depression and anxiety,which affect their sleep quality and post-traumatic growth levels.AIM To investigate the effects of sepsis,a one-hour bundle(H1B)management was combined with psychological intervention in patients with sepsis.METHODS This retrospective analysis included 300 patients with sepsis who were admitted to Henan Provincial People’s Hospital between June 2022 and June 2023.According to different intervention methods,the participants were divided into a simple group(SG,n=150)and combined group(CG,n=150).H1B management was used in the SG and H1B management combined with psychological intervention was used in the CG.The changes of negative emotion,sleep quality and post-traumatic growth and prognosis were compared between the two groups before(T0)and after(T1)intervention.RESULTS After intervention(T1),the scores of the Hamilton Anxiety scale and Hamilton Depression scale in the CG were significantly lower than those in the SG(P<0.001).Sleep time,sleep quality,sleep efficiency,daytime dysfunction,sleep disturbance dimension score,and the total score in the CG were significantly lower than those in the SG(P<0.001).The appreciation of life,mental changes,relationship with others,personal strength dimension score,and total score of the CG were significantly higher than those of the SG(P<0.001).The scores for mental health,general health status,physiological function,emotional function,physical pain,social function,energy,and physiological function in the CG were significantly higher than those in the SG(P<0.001).The mechanical ventilation time,intensive care unit stay time,and 28-d mortality of the CG were significantly lower than those of the SG(P<0.05).CONCLUSION H1B management combined with psychological intervention can effectively alleviate the negative emotions of patients with sepsis and increase their quality of sleep and life.

Sepsis Prediction Using CNNBDLSTM and Temporal Derivatives Feature Extraction in the IoT Medical Environment

Background:Sepsis,a potentially fatal inflammatory disease triggered by infection,carries significant healthimplications worldwide.Timely detection is crucial as sepsis can rapidly escalate if left undetected.Recentadvancements in deep learning(DL)offer powerful tools to address this challenge.Aim:Thus,this study proposeda hybrid CNNBDLSTM,a combination of a convolutional neural network(CNN)with a bi-directional long shorttermmemory(BDLSTM)model to predict sepsis onset.Implementing the proposed model provides a robustframework that capitalizes on the complementary strengths of both architectures,resulting in more accurate andtimelier predictions.Method:The sepsis prediction method proposed here utilizes temporal feature extraction todelineate six distinct time frames before the onset of sepsis.These time frames adhere to the sepsis-3 standardrequirement,which incorporates 12-h observation windows preceding sepsis onset.All models were trained usingthe Medical Information Mart for Intensive Care III(MIMIC-III)dataset,which sourced 61,522 patients with 40clinical variables obtained from the IoT medical environment.The confusion matrix,the area under the receiveroperating characteristic curve(AUCROC)curve,the accuracy,the precision,the F1-score,and the recall weredeployed to evaluate themodels.Result:The CNNBDLSTMmodel demonstrated superior performance comparedto the benchmark and other models,achieving an AUCROC of 99.74%and an accuracy of 99.15%one hour beforesepsis onset.These results indicate that the CNNBDLSTM model is highly effective in predicting sepsis onset,particularly within a close proximity of one hour.Implication:The results could assist practitioners in increasingthe potential survival of the patient one hour before sepsis onset.

Predictive value of systemic immunity index for sepsis in low-medium risk community-acquired pneumonia

Objective:To assess the predictive value of systemic immune inflammation index(SII)for sepsis in low-and medium-risk community-acquired pneumonia.Methods:A total of 589 elderly patients with low-and medium-risk community-acquired pneumonia admitted to the Emergency Department of the Second Affiliated Hospital of Hainan Medical University from January 2020 to January 2023 were included as the research subjects,and the general information and laboratory test results of the patients were collected,and the optimal cut-off value of continuous variables for predicting sepsis in elderly patients with low-and medium-risk community-acquired pneumonia was determined by plotting the receiver work characteristic(ROC)curve,which was converted into dichotomous variables and univariate and multivariate logistic Regression analysis of the influencing factors of sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.Based on this,a nomogram model is constructed to predict the risk of sepsis.The differentiation,consistency and accuracy of the model were verified by calibration curve and subject operating characteristic(ROC)curve,and the clinical utility of the model was determined by decision curve analysis.Results:A total of 589 elderly patients with low-and intermediate-risk community-acquired pneumonia were included in this study,of which 96(16.30%)developed sepsis.There were significant differences in age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,PCT,SII and other indexes between sepsis and non-sepsis groups(P<0.05).Logistics regression analysis showed that age,diabetes mellitus and chronic obstructive pulmonary disease,Lac,and SII were independent risk factors for sepsis in elderly patients with low-and medium-risk community-acquired pneumonia.The nomogram prediction model was used to verify the results,and the AUC was 0.826(95%CI:0.780-0.872),and the calibration curve tended to the ideal curve with good accuracy.The decision curve shows that when the threshold of the model is between 0.10~0.78,the model has the advantage of clinical benefit.Conclusion:The nomogram prediction model constructed based on SII to predict sepsis in elderly patients with low-and medium-risk community-acquired pneumonia has good accuracy,which can predict the occurrence of sepsis early,help early identification of high-risk groups and timely intervention,and thus improve the prognosis of patients.

Effect of early stepwise cardiopulmonary rehabilitation on function and quality of life in sepsis patients

BACKGROUND Sepsis,as a non-limiting host infection disease,can be accompanied by serious complications such as organ failure,which seriously threatens patient quality of life.AIM To investigate the effect of early stepwise cardiopulmonary rehabilitation on cardiopulmonary function and quality of life in patients evacuated from mechanical ventilation with sepsis.METHODS A total of 80 patients with sepsis who were hospitalized in our hospital from January 2021 to January 2022 were selected and divided into the observation group(n=40)and the control group(n=40)according to the random number table method.The observation group was treated with early stepwise cardiopulmonary rehabilitation,and the control group was treated with a conventional treatment regimen.Cardiac function indexes(central venous pressure,cardiac troponin I,B-type brain natriuretic peptide),lung function indicators(diaphragmatic mobility,changes in central venous oxygen saturation,oxygenation index),and quality of life(Quality of Life Evaluation Scale)were compared between the two groups after treatment.RESULTS After treatment,the central venous pressure,diaphragm mobility,central venous oxygen saturation,oxygenation index,and Quality of Life Evaluation Scale scores in the observation group were higher than those in the control group,and the differences were statistically significant(P<0.05).The observation group was less than that of the control group for other parameters,and the differences were statistically significant(P<0.05).CONCLUSION Early stepwise cardiopulmonary rehabilitation can effectively enhance cardiac and pulmonary function and improve the quality of life in patients evacuated from mechanical ventilation with sepsis.

Study of the OPG/RANKL/RANK signaling pathway in mice treated with sepsis-related acute kidney injury

Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.

Oleuropein alleviates sepsis-induced acute lung injury via the AMPK/Nrf-2/HO-1 signaling

Objective:To explore the effect of oleuropein on sepsis-induced acute lung injury(ALI)in vitro and in vivo and investigate the underlying mechanism.Methods:In an lipopolysaccharide(LPS)-mediated cell model of sepsis-induced ALI and a cecal ligation and puncture-induced mouse model of septic ALI,CCK-8 assay and flow cytometry analysis were used to detect cell activity and apoptosis.ELISA and relevant assay kits were used to measure the levels of inflammatory cytokines and oxidative stress,respectively.Western blot was applied to determine the expression of apoptosis-and AMP-activated protein kinase(AMPK)/nuclear factor erythroid 2-related factor-2(Nrf-2)/heme oxygenase-1(HO-1)signaling-associated proteins.JC-1 staining,adenosine triphosphate(ATP)assay kit,and MitoSOX Red assays were performed to detect mitochondrial membrane potential,ATP content,and mitochondrial ROS formation,respectively.Moreover,lung injury was evaluated by measuring lung morphological alternations,lung wet-to-dry ratio,myeloperoxidase content,and total protein concentration.Results:Oleuropein reduced inflammatory reaction,oxidative damage,and apoptosis,and ameliorated mitochondrial dysfunction in LPS-exposed BEAS-2B cells and mice with septic ALI.Besides,oleuropein activated the AMPK/Nrf-2/HO-1 signaling pathway.However,these effects of oleuropein were abrogated by an AMPK inhibitor compound C.Conclusions:Oleuropein can protect against sepsis-induced ALI in vitro and in vivo by activating the AMPK/Nrf-2/HO-1 signaling,which might be a potential therapeutic agent for the treatment of sepsis-induced ALI.

Clinical significance of platelet mononuclear cell aggregates in patients with sepsis and acute respiratory distress syndrome

BACKGROUND The diagnosis of sepsis combined with acute respiratory distress syndrome(ARDS)has increased owing to the enhanced awareness among medical profes-sionals and the continuous development of modern medical technologies,while early diagnosis of ARDS still lacks specific biomarkers.One of the main patho-genic mechanisms of sepsis-associated ARDS involves the actions of various pathological injuries and inflammatory factors,such as platelet and white blood cells activation,leading to an increase of surface adhesion molecules.These adhesion molecules further form platelet-white blood cell aggregates,including platelet-mononuclear cell aggregates(PMAs).PMAs has been identified as one of the markers of platelet activation,here we hypothesize that PMAs might play a potential biomarker for the early diagnosis of this complication.METHODS We selected 72 hospitalized patients diagnosed with sepsis as the study population between March 2019 and March 2022.Among them,30 patients with sepsis and ARDS formed the study group,while 42 sepsis patients without ARDS comprised the control group.After diagnosis,venous blood samples were imme-diately collected from all patients.Flow cytometry was employed to analyze the expression of PMAs,platelet neutrophil aggregates(PNAs),and platelet aggregates(PLyAs)in the serum.Additionally,the Acute Physiology and Chronic Health Evaluation(APACHE)II score was calculated for each patient,and receiver operating characteristic curves were generated to assess diagnostic value.RESULTS The study found that the levels of PNAs and PLyAs in the serum of the study group were higher than those in the control group,but the difference was not statistically significant(P>0.05).However,the expression of PMAs in the serum of the study group was significantly upregulated(P<0.05)and positively correlated with the APACHE II score(r=0.671,P<0.05).When using PMAs as a diagnostic indicator,the area under the curve value was 0.957,indicating a high diagnostic value(P<0.05).Furthermore,the optimal cutoff value was 8.418%,with a diagnostic sensitivity of 0.819 and specificity of 0.947.CONCLUSION In summary,the serum levels of PMAs significantly increase in patients with sepsis and ARDS.Therefore,serum PMAs have the potential to become a new biomarker for clinically diagnosing sepsis complicated by ARDS.

Predictive value of thrombocytopenia for bloodstream infection in patients with sepsis and septic shock

BACKGROUND Thrombocytopenia is common in patients with sepsis and septic shock.AIM To analyse the decrease in the number of platelets for predicting bloodstream infection in patients with sepsis and septic shock in the intensive care unit.METHODS A retrospective analysis of patients admitted with sepsis and septic shock in Xingtai People Hospital was revisited.Patient population characteristics and laboratory data were collected for analysis.RESULTS The study group consisted of 85(39%)inpatients with bloodstream infection,and the control group consisted of 133(61%)with negative results or contamination.The percentage decline in platelet counts(PPCs)in patients positive for pathogens[57.1(41.3-74.6)]was distinctly higher than that in the control group[18.2(5.1–43.1)](P<0.001),whereas the PPCs were not significantly different among those with gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.Using receiver operating characteristic curves,the area under the curve of the platelet drop rate was 0.839(95%CI:0.783-0.895).CONCLUSION The percentage decline in platelet counts is sensitive in predicting bloodstream infection in patients with sepsis and septic shock.However,it cannot identify gram-positive bacteraemia,gram-negative bacteraemia,and fungal infection.