Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation.

OBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. DESIGN: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study. SETTING: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation. PATIENTS OR SUBJECTS: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia. INTERVENTIONS: During our comparison, we did not perform any intervention. MEASUREMENTS AND MAIN RESULTS: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites. CONCLUSIONS: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.

Exploring the circulating metabolome of sepsis: metabolomic and lipidomic profiles sampled in the ambulance.

BACKGROUND: Sepsis is defined as a dysfunctional host response to infection. The diverse clinical presentations of sepsis pose diagnostic challenges and there is a demand for enhanced diagnostic markers for sepsis as well as an understanding of the underlying pathological mechanisms involved in sepsis. From this perspective, metabolomics has emerged as a potentially valuable tool for aiding in the early identification of sepsis that could highlight key metabolic pathways and underlying pathological mechanisms. OBJECTIVE: The aim of this investigation is to explore the early metabolomic and lipidomic profiles in a prospective cohort where plasma samples (n = 138) were obtained during ambulance transport among patients with infection according to clinical judgement who subsequently developed sepsis, patients who developed non-septic infection, and symptomatic controls without an infection. METHODS: Multiplatform metabolomics and lipidomics were performed using UHPLC-MS/MS and UHPLC-QTOFMS. Uni- and multivariable analysis were used to identify metabolite profiles in sepsis vs symptomatic control and sepsis vs non-septic infection. RESULTS: Univariable analysis disclosed that out of the 457 annotated metabolites measured across three different platforms, 23 polar, 27 semipolar metabolites and 133 molecular lipids exhibited significant differences between patients who developed sepsis and symptomatic controls following correction for multiple testing. Furthermore, 84 metabolites remained significantly different between sepsis and symptomatic controls following adjustment for age, sex, and Charlson comorbidity score. Notably, no significant differences were identified in metabolites levels when comparing patients with sepsis and non-septic infection in univariable and multivariable analyses. CONCLUSION: Overall, we found that the metabolome, including the lipidome, was decreased in patients experiencing infection and sepsis, with no significant differences between the two conditions. This finding indicates that the observed metabolic profiles are shared between both infection and sepsis, rather than being exclusive to sepsis alone.

Single-cell RNA sequencing and immune repertoire analysis revealed dynamic immune characteristics associated with peripheral blood during sepsis.

Sepsis is a potentially fatal condition arising from an abnormal immune response to an infection, which can result in organ failure and even death. To explore the mechanism underlying the dysregulated immune response during sepsis and identify potential therapeutic targets, single-cell RNA sequencing (scRNA-seq) and immune repertoire analysis were conducted to depict the cellular landscape of peripheral blood cells in septic mice. We observed significant alterations in the number and proportion of peripheral blood cell populations driven by sepsis. By combining single-cell gene expression profiles and B cell receptor (BCR) repertoire analysis, we discerned that infection inflicted serious damage on the antigen presentation ability of B cells and the diversity of BCR in a short time. In addition, we found that the cecal ligation and puncture procedure in mice inhibited the communication signals of CD4+ and CD8+ T cells and decreased the interactions between B cells and other cells. Our study provides detailed insights into the dynamic changes in the biological characteristics of peripheral blood cells driven by sepsis and provides important advances in our understanding of immune disorders during sepsis.

A retrospective study utilized MIMIC-IV database to explore the potential association between triglyceride-glucose index and mortality in critically ill patients with sepsis.

Triglyceride-glucose (TyG) index has emerged as a novel biomarker for detecting insulin resistance (IR) and has been proven to be associated with various diseases. However, its correlation with the prognosis of severe sepsis remains unraveled. This retrospective cohort study utilized patient records from the Medical Information Mart for Intensive Care (MIMIC-IV, version 2.2) to examine the outcomes of patients with sepsis. The primary outcomes were hospital mortality and intensive care unit (ICU) mortality. The correlation between the TyG index and outcomes was evaluated through the Kaplan-Meier method, the Log-rank test, and univariate and multivariate Cox regression analyses. Additionally, restricted cubic spline (RCS) regression analysis was employed to delve into the nonlinear relationship between baseline TyG index and outcomes, with trend significance assessed through quartile levels. Subgroup analyses were conducted to evaluate the consistency of the TyG index's prognostic value across various influencing factors. The study included 1,742 patients with sepsis requiring intensive care. The in-hospital mortality rate was 19.75% (344/1,742), and the ICU mortality rate was 14.75% (257/1,742). Cox regression analysis revealed that, in comparison to the first quartile (Q1), patients in the fourth quartile (Q4) had a 63% higher risk of in-hospital mortality (HR 1.63 [95% CI 1.22 to 2.18], P < 0.01) and a 79% higher risk of ICU mortality (HR 1.79 [95% CI 1.28 to 2.51], P < 0.001). Model 3 showed that ICU mortality risks for Q4, Q3, and Q2 were 240%, 75%, and 33% higher, respectively (HR 3.40 [95% CI 2.24 to 5.16], P < 0.001; HR 1.75 [95% CI 1.16 to 2.63], P = 0.007; HR 1.33 [95% CI 1.20 to 1.53], P < 0.001). RCS regression analysis identified a nonlinear association between the TyG index and mortality (overall P < 0.001; P for nonlinearity < 0.001, with an inflection point at 8.9). Subgroup analysis showed that the effect size and direction were consistent across different subgroups, suggesting the stability of the results. This study demonstrates that a higher TyG index is significantly associated with increased in-hospital and ICU mortality risk in critically ill sepsis patients, with evidence of non-linear correlation. Therefore, the TyG index helps identify the mortality prognosis of sepsis patients in the ICU.

Role of CD64 and myeloperoxidase as biomarkers for early diagnosis of sepsis in pediatric intensive care unit.

Globally, sepsis is the primary cause of death for children. While research conducted on adults has a significant impact on the diagnosis and treatment of sepsis in newborns and young children, there are significant factors that are pertinent to pediatrics as well. This prospective case-control study was conducted during the period from August 2020 to October 2022 after approval by the institutional ethical committee. The study included 48 critically ill children admitted at the Pediatric intensive care unit and 30 apparently healthy children as a control group. Laboratory investigations including complete blood picture, C-reactive protein (CRP), blood culture and sensitivity and plasma level of cluster of differentiation 64 (CD64) and myeloperoxidase (MPO) were investigated for all participants. A daily follow up for the signs of systemic inflammatory response syndrome (SIRS) or sepsis was done, and the patients were divided into SIRS and non-SIRS subgroups then patients were divided into two groups according to the presence of severe sepsis. A follow up CD64 and MPO sample were withdrawn from them to assess their prognostic value. SIRS was reported in 39.58 % of patients while severe sepsis was reported in 20.8%. CD64 and MPO were significantly higher in cases than controls (p= 0.003, p < 0.001, respectively) and, in patients with SIRs and severe sepsis CD64 was 1559.00± 367.09 pg/ml and 1547.9 4± 436.14 pg/ml, respectively. Also, MPO was significantly higher in patients with SIRS (113.58± 25.19 mU/ml) and severe sepsis (111.70± 26.50 mU/ml). CD64 and MPO significantly increased after development of sepsis in admitted patients. ROC was significantly higher for CD64 and MPO at admission than that for CRP at admission (p=0.123, p=0.014, respectively). In conclusion, plasma level of CD64 and MPO in peripheral blood can be considered an early sensitive marker for the detection and follow up of pediatric sepsis.

Procalcitonin-Guided Management and Duration of Antibiotic Therapy in Critically Ill Cancer Patients With Sepsis (Pro-Can Study): A Randomized Controlled Trial.

OBJECTIVES: To evaluate the effect of procalcitonin-guided management on the duration of antibiotic therapy in critically ill cancer patients with sepsis. DESIGN: Randomized, controlled, single-blinded trial. SETTING: A comprehensive multidisciplinary cancer hospital in Jordan. PATIENTS: Adults with cancer treated in the ICU who were started on antibiotics for suspected infection, met the SEPSIS-3 criteria, and were expected to stay in the ICU greater than or equal to 48 hours. INTERVENTIONS: Patients were randomized to the procalcitonin-guided or standard care (SC) arms. All patients had procalcitonin measured daily, up to 5 days or until ICU discharge or death. For the procalcitonin arm, a procalcitonin-guided algorithm was provided to guide antibiotic management, but clinicians were allowed to override the algorithm, if clinically indicated. In the SC arm, ICU clinicians were blinded to the procalcitonin levels. MEASUREMENTS AND MAIN RESULTS: Primary outcome was time to antibiotic cessation. We also evaluated the number of antibiotic-free days at 28 days, hospital discharge, or death, whichever came first, and antibiotic defined daily doses (DDDs). We enrolled 77 patients in the procalcitonin arm and 76 in the SC arm. Mean age was 58 ± 14 (sd) years, 67% were males, 74% had solid tumors, and 13% were neutropenic. Median (interquartile range [IQR]) Sequential Organ Failure Assessment scores were 7 (6-10) and 7 (5-9) and procalcitonin concentrations (ng/mL) at baseline were 3.4 (0.8-16) and 3.4 (0.5-26), in the procalcitonin and SC arms, respectively. There was no difference in the median (IQR) time to antibiotic cessation in the procalcitonin and SC arms, 8 (4-11) and 8 (5-13), respectively (p = 0.463). Median (IQR) number of antibiotic-free days were 20 (17-24) and 20 (16-23), (p = 0.484) and total DDDs were 1541.4 and 2050.4 in the procalcitonin and SC arms, respectively. CONCLUSIONS: In critically ill cancer patients with sepsis, procalcitonin-guided management did not reduce the duration of antibiotic treatment.

Damage-associated molecular patterns in bacteraemic infection, including a comparative analysis with bacterial DNA, a pathogen-associated molecular pattern.

Damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) are key triggers of inflammation in sepsis. However, they have rarely been studied simultaneously. Thus, in the present study of patients with bacteraemic infection, we aimed to study how DAMP dynamics are linked to disease severity and outcome and to compare diagnostic and prognostic properties of a DAMP and a previously analysed PAMP (16S rDNA). In a prospective study of adult patients hospitalized with culture-proven community-onset bacteraemic infection, caused by Streptococcus pneumonia (n = 30), Staphylococcus aureus (n = 27), or Escherichia coli (n = 26), dynamics of a PAMP, i.e. 16S rDNA, have previously been presented. For the present study, blood samples obtained on hospital days 1-2 (when blood culture was positive), 3-4, 7 ± 1, 14 ± 2, and 28 ± 4 were analysed for four different DAMPs, i.e., nuclear DNA (nDNA), mitochondrial DNA (mtDNA), heat shock protein 90 alpha (HSP90α), and extracellular high mobility group box 1 (HMGB1). Sepsis was defined according to the Sepsis-3 criteria. The study outcomes were sepsis at admission and negative outcome, defined as intensive care unit (ICU) admission and/or death within 60 days. Of 83 study patients, sepsis was noted in 41 patients (49%) and a negative outcome was noted in 17 patients (20%). nDNA had areas under the receiver operating characteristic (ROC) curves of 0.78 for sepsis and 0.76 for negative outcome, which were higher than those of the other DAMPs and additional biomarkers (CRP, IL-6, IL-8, and IL-10). The nDNA and positive 16S rDNA results on day 1-2 were correlated with each other (r = 0.68, p < 0.001). Multivariate analyses showed that high day 1-2 concentrations of both nDNA and 16S rDNA were independently associated with sepsis. In addition, high day 1-2 concentration of nDNA was independently associated with negative outcomes. While 16S rDNA dissipated from the circulation within days, nDNA concentrations remained elevated throughout the follow-up period in patients with negative outcome. In conclusion, nDNA outperformed the other DAMPs regarding sepsis detection and outcome prediction. Both nDNA (a DAMP) and 16S rDNA (a PAMP) were independently linked to sepsis; nDNA was also associated with negative outcomes and persisted elevated in such cases. This highlights nDNA as an interesting marker within sepsis pathogenesis and as a promising clinical biomarker, warranting further studies.

A dataset for developing proteomic tools for pathogen detection via differential cell lysis of whole blood samples.

This data descriptor presents a curated dataset for pathogen detection and identification (Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) directly from whole-blood samples. The dataset was created using differential cell lysis combined with rapid extraction, digestion, and mass spectrometry-based proteomics. Our method offers a rapid diagnostic alternative to traditional culture, enabling timely disease management, such as sepsis. Highlighting our dataset's uniqueness, it features a three-tier structure: Spectral Libraries of Pathogens for identifying peptide peaks for putative biomarkers; Spiked pathogen in blood MS data for biomarker panel optimization through varied concentration samples; and Parallel Reaction Monitoring (PRM) data from sepsis patients for validating our biomarker panel, achieving 83.3% sensitivity within seven hours without microbial enrichment culture. This dataset serves as a comprehensive reference for bioinformatic tool development and biomarker panel proposals, advancing microbial detection, antimicrobial resistance, and epidemiological studies.

The performance of screening tools and use of blood analyses in prehospital identification of sepsis patients and patients suitable for non-conveyance - an observational study.

BACKGROUND: Early recognition of sepsis by the EMS (Emergency Medical Services), along with communicating this concern to the emergency department, could improve patient prognosis and outcome. Knowledge is limited about the performance of sepsis identification screening tools in the EMS setting. Research is also limited on the effectiveness of prehospital use of blood tests for sepsis identification. Integrating blood analyses with screening tools could improve sepsis identification, leading to prompt interventions and improved patient outcomes. AIM: The aim of the present study is firstly to evaluate the performance of various screening tools for sepsis identification in the EMS setting and secondly to assess the potential improvement in accuracy by incorporating blood analyses. METHODS: This is a retrospective observational cohort study. The data were collected from prehospital and hospital medical records in Region Halland. Data on demographics, vital signs, blood tests, treatment, and outcomes were collected from patients suspected by EMS personnel of having infection. The data were analysed using Student's t-test. Sensitivity, specificity, positive predictive value, negative predictive value and odds ratio were used to indicate accuracy and predictive value. RESULTS: In total, 5,405 EMS missions concerning 3,225 unique patients were included. The incidence of sepsis was 9.8%. None of the eleven tools included had both high sensitivity and specificity for sepsis identification. White blood cell (WBC) count was the blood analysis with the highest sensitivity but the lowest specificity for identifying sepsis. Adding WBC, C-reactive protein (CRP) or lactate to the National Early Warning Score (NEWS) increased the specificity to > 80% but substantially lowered the sensitivity. CONCLUSIONS: Identifying sepsis in EMS settings remains challenging, with existing screening tools offering limited accuracy. CRP, WBC, and lactate blood tests add minimal predictive value in distinguishing sepsis or determining non-conveyance eligibility.

Exploring the prognostic and diagnostic value of lactylation-related genes in sepsis.

The discovery of Lactylation may pave the way for novel approaches to investigating sepsis. This study focused on the prognostic and diagnostic significance of lactylated genes in sepsis. RNA sequencing was performed on blood samples from 20 sepsis patients and 10 healthy individuals at Southwest Medical University in Luzhou, Sichuan, China. Genes associated with sepsis were identified through analysis of RNA sequencing data. Afterward, the genes that were expressed differently were compared with the lactylation genes, resulting in the identification of 55 lactylation genes linked to sepsis. The overlapping genes underwent analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-Protein Network Interactions were used to screen for the core genes. The datasets GSE65682, GSE69528, GSE54514, GSE63042, and GSE95233 were obtained from the GEO database to validate core genes. Survival analysis evaluated the predictive significance of central genes in sepsis, while Receiver Operating Characteristic (ROC) Curve analysis was employed to establish the diagnostic value of genes. Additionally, a meta-analysis was conducted to confirm the precision of RNA-seq data. We obtained five peripheral blood samples, including two from healthy individuals, one from a patient with systemic inflammatory response syndrome (SIRS), and two from patients with sepsis. These samples were used to identify the specific location of core genes using 10×single-cell sequencing. High-throughput sequencing and bioinformatics techniques identified two lactylation-related genes (S100A11 and CCNA2) associated with sepsis. Survival analysis indicated that septic patients with reduced levels of S100A11 had a decreased 28-day survival rate compared to those with elevated levels. Conversely, individuals exhibiting decreased CCNA2 levels demonstrated a greater likelihood of surviving for 28 days than those in the high expression category, indicating a favorable association with survival rates among sepsis patients (P < 0.05). Both genes showed high sensitivity and specificity based on the ROC curve, with AUC values of 0.961 for S100A11 and 0.890 for CCNA2. The meta-analysis revealed that S100A11 exhibited high levels of expression in the sepsis survivors, whereas it displayed low levels of expression in the non-survivors; on the other hand, CCNA2 demonstrated low expression in the sepsis survivors and high expression in the non-survivors (P < 0.05). Single-cell RNA sequencing ultimately showed that monocyte macrophages, T cells, and B cells exhibited high expression levels of the crucial genes associated with sepsis-induced lactylation. In conclusion, the lactylation genes S100A11 and CCNA2 are strongly linked to sepsis and could be valuable markers for diagnosing, predicting outcomes, and providing guidance for sepsis.

Advanced biomarker clustering analysis reveals mortality predictors in burn patients with sepsis.

This study addresses the challenge of predicting mortality in sepsis among burn patients. Given the heterogeneity of sepsis, especially in the context of burn injuries, this study aims to identify reliable biomarkers for mortality prediction. The study is a retrospective review, focusing on the evaluation of various biomarkers and their changes over time in a burn patient cohort. Conducted in the Burn Intensive Care Unit of Hangang Sacred Heart Hospital, the study involved a retrospective review of 1,659 adult burn patients from January 2010 to December 2022. Key biomarkers analyzed include lactate levels, pH, platelets, procalcitonin, and others. Advanced clustering methodologies, such as dynamic time warping and hierarchical clustering, were utilized to classify patients into distinct groups based on their biomarker profiles and clinical outcomes. The study identified four patient clusters with unique lactate level trajectories. Significant findings include the identification of procalcitonin, pH, and platelets as key predictors of mortality, with varying degrees of efficacy across different clusters. For instance, in the "Persistent Rise" cluster, pH and platelet count showed Area Under the Curve (AUC) values of 0.756 and 0.753, respectively, indicating their strong predictive power. The study concludes that a combination of biomarkers, especially lactate dynamics, can effectively predict mortality in burn-induced sepsis. The results advocate for a more personalized approach in managing sepsis in burn patients, considering the specific biomarker trajectories. These findings are crucial for enhancing treatment strategies and improving patient outcomes in burn care.

The triglyceride-glucose index dynamic trajectory reveals the association between the clinical subphenotype of insulin resistance and mortality in patients with sepsis.

BACKGROUND: The relationship between the dynamic changes in insulin resistance (IR) and the prognosis of septic patients remains unclear. This study aims to investigate the correlation between the clinical subphenotype of IR represented by the triglyceride-glucose (TyG) index trajectory and the mortality rate among patients with sepsis. METHODS: In this retrospective cohort study, we utilized data from septic patients within the Medical Information Mart for Intensive Care (MIMIC)-IV database version 2.0 to construct trajectories of the TyG index over 72 h. Subsequently, we computed the similarity among various TyG index trajectories with the dynamic time warping (DTW) algorithm and utilized the hierarchical clustering (HC) algorithm to demarcate distinct cluster and identified subphenotypes according to the trajectory trend. Subsequently, we assessed the mortality risk between different subphenotypes using analyses such as survival analysis and validated the robustness of the results through propensity score matching (PSM) and various models. RESULTS: A total of 2350 patients were included in the study. Two trajectory trends: TyG index decreasing (n = 926) and TyG index increasing (n = 1424) were identified, which indicated corresponding to the clinical subphenotype of increased and alleviative IR respectively. The 28-day and in-hospital mortality for the increased IR group was 28.51% and 25.49% respectively. In comparison, patients in the alleviative IR group with a 28-day mortality of 23.54% and an in-hospital mortality of 21.60%. These subphenotypes exhibited distinct prognosis, time dependent Cox model showed the increased IR group with a higher 28-day mortality [hazard ratio (HR): 1.07, 95% confidence interval (CI): 1.02-1.12, P = 0.01] and in-hospital mortality [HR: 1.05, 95% CI: 1.00-1.11, P = 0.045] compared to the alleviative IR group. Sensitivity analyses with various models further validated the robustness of our findings. CONCLUSION: Dynamic increase in the TyG index trajectory is associated with elevated mortality risk among patients with sepsis, which suggests that dynamic increased IR exacerbates the risk of poor outcomes in patients.

Early B lymphocyte subsets in blood predict prognosis in sepsis.

Background: B lymphocytes play a key role in immunosuppression. This study investigated the prognostic value of B cell subsets in sepsis. Methods: Flow cytometry was used to assess peripheral B cell subsets from patients with sepsis on the first and seventh days following admission, as well as 111 healthy controls. The patients were divided into survivors and non-survivors, based on 28-day prognosis. Results: The analysis showed abnormal distribution and selective depletion of B cells and its subsets in the early stages of sepsis. On day 1, compared with survivors, non-survivors showed significant decreases in the proportion and absolute count of transitional (Tr) B cells, reductions in the proportion of CD5+ B cells, and increases in the proportion of double-negative (DN) B cells. On day 7, the proportions and absolute counts of Tr and CD5+ B cells significantly decreased whereas the proportion of DN B cells significantly increased in non-survivors. Ninety-four survivors and 15 non-survivors were included in our paired-sample rank-sum test. Compared to day 1, only the survivors showed significant increases in absolute B, Tr B, and CD5+ B cell counts by day 7. Multivariate Cox regression analysis showed that the proportion of DN B cells on day 1 (hazard ratio = 1.092 [95% confidence interval: 1.035-1.152], P = 0.001) was a risk factor for mortality, and Kaplan-Meier survival curve analysis showed that patients with proportions of DN B cells > 11.81% on day 1 had poorer prognoses. Receiver operating characteristic curve analysis showed that B cell subset parameters could predict mortality (area under the receiver operating characteristic curve [AUC], 0.741) and enhanced the prognostic value of the Acute Physiology and Chronic Health Evaluation II score (AUC, 0.840). Conclusion: Our study revealed that deficiencies of B, Tr B, and CD5+ B cells, as well as a persistent increase in the proportion of DN B cells, were associated with poor prognosis-and that B cell subsets showed predictive value to mortality. These results provide new insights into the roles of B cell subsets in sepsis, as well as ways to better manage its progression and predict its course.

Prognostic value of red blood cell distribution width in sepsis induced cardiomyopathy patients.

The potential association between red blood cell distribution width (RDW) at admission and prognosis in patients with sepsis-induced cardiomyopathy(SIC) remains uncertain. The purpose of this study was to explore the prognostic value of RDW on mortality in patients with SIC. Data for this retrospective study were obtained from the MIMIC IV2.2 database. We used propensity score matching (PSM) and Cox proportional hazards regression analysis to evaluate the main risk factors associated with mortality in SIC patients. This analysis was utilized to develop a predictive nomogram. To assess the predictive accuracy and clinical usefulness of the model, we employed the concordance index (C-index) and decision curve analysis. To define the high- and low-RDW groups among patients with SIC, we determined the optimal cut-off value by maximizing the Youden index. According to the screening criteria, we identified a cohort of 1051 patients diagnosed with SIC. When comparing the high-RDW group to the low-RDW group, it was found that the high-RDW group exhibited longer Los_ICU(4.5 days vs.3.8 days, respectively, P = 0.009) and higher mortality rates at 28 days (33.8% vs. 7.8%, respectively, P < 0.001). A nomogram model was created using matched patients which included various factors such as Age, RDW, LDH, CKMB, creatinine and the administration of ß-blocker. The C-index predicting 28-day survival probability was 0.846. Decision curves analysis demonstrated that the inclusion of RDW in the model provided a greater net benefit compared to excluding RDW. The prognosis of patients with SIC can be predicted by the RDW value. The nomogram model provides a useful tool in identifying and managing SIC patients.

Elevated Triglyceride-Glucose (TyG) Index Predicts Poor Clinical Outcomes in Critically Ill AECOPD Patients: A Retrospective Study.

Purpose: The triglyceride-glucose (TyG) index is a surrogate biomarker of insulin resistance which has been widely used in intensive care unit (ICU) to predict prognosis. However, its role in critically ill acute exacerbation of COPD (AECOPD) patients remains largely unknown. Material and methods: A total of 645 AECOPD patients were induced in this retrospective cohort study, which extracted data from the eICU Collaborative Research Database (eICU-CRD). The TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). The primary endpoint includes in-hospital mortality and ICU mortality. The secondary endpoint was sepsis, acute kidney injury (AKI), and acute respiratory failure (ARF). Results: Multivariable Cox regression analysis revealed that the TyG index was independently associated with an increased risk of in-hospital mortality (hazard ratio, HR: 1.45, 95% CI: 1.04-2.01, P = 0.028) and ICU mortality (HR: 2.13, 95% CI: 1.28-3.54, P = 0.004). Moreover, the TyG index was independently associated with an increased risk of sepsis (odds ratio, OR: 1.54, 95% CI: 1.24-1.93, P < 0.001), AKI (OR: 1.57, 95% CI: 1.26-2.02, P < 0.001) and ARF (OR: 1.50, 95% CI: 1.20-1.87, P < 0.001). Kaplan-Meier survival analysis revealed that higher TyG indexes were also related to increased in-hospital mortality and ICU mortality. In addition, the restricted cubic splines regression model demonstrated that the in-hospital mortality and ICU mortality increased linearly with increasing TyG index (P for non-linearity = 0.897, P for non-linearity = 0.897, respectively). Conclusion: Elevated TyG index was independently associated with an increased risk of poor clinical outcomes in critically ill AECOPD patients. A prospective study to define TyG as a biomarker for prognosis prediction in critically ill AECOPD patients is warranted.

The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study.

In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1ß, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1ß and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.

A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that is associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) may provide new insight into understanding and identifying SI-AKI. Plasma cfDNA from 82 healthy individuals, 7 patients with sepsis non-acute kidney injury (SN-AKI), and 9 patients with SI-AKI was subjected to genomic methylation sequencing. We deconstructed the relative contribution of cfDNA from different cell types based on cell-specific methylation markers and focused on exploring the association between kidney-derived cfDNA and SI-AKI.Based on the deconvolution of the cfDNA methylome: SI-AKI patients displayed the elevated cfDNA concentrations with an increased contribution of kidney epithelial cells (kidney-Ep) DNA; kidney-Ep derived cfDNA achieved high accuracy in distinguishing SI-AKI from SN-AKI (AUC = 0.92, 95% CI 0.7801-1); the higher kidney-ep cfDNA concentrations tended to correlate with more advanced stages of SI-AKI; strikingly, SN-AKI patients with potential kidney damage unmet by SI-AKI criteria showed higher levels of kidney-Ep derived cfDNA than healthy individuals. The autonomous screening of kidney-Ep (n = 24) and kidney endothelial (kidney-Endo, n = 12) specific methylation markers indicated the unique identity of kidney-Ep/kidney-Endo compared with other cell types, and its targeted assessment reproduced the main findings of the deconvolution of the cfDNA methylome. Our study first demonstrates that kidney-Ep- and kidney-Endo-specific methylation markers can serve as a novel marker for SI-AKI emergence, supporting further exploration of the utility of kidney-specific cfDNA methylation markers in the study of SI-AKI.

Stronger association of intact angiotensinogen with mortality than lactate or renin in critical illness: post-hoc analysis from the VICTAS trial.

Sepsis and septic shock remain global healthcare problems associated with high mortality rates despite best therapy efforts. Circulating biomarkers may identify those patients at risk for poor outcomes, however, current biomarkers, most prominently lactate, are non-specific and have an inconsistent impact on prognosis and/or disease management. Activation of the renin-angiotensin- system (RAS) is an early event in sepsis patients and elevated levels of circulating renin are more predictive of worse outcomes than lactate. The precursor protein Angiotensinogen is another key component of the circulating RAS; it is the only known substrate for renin and the ultimate source of the vasopressor Angiotensin II (Ang II). We postulate that lower Angiotensinogen concentrations may reflect a dysfunctional RAS characterized by high renin concentrations but attenuated Ang II generation, which is disproportionate to the high renin response and may compromise adequate support of blood pressure and tissue perfusion in septic patients. The current study compared the association between serum Angiotensinogen with mortality to that of lactate and renin in the VICTAS cohort of sepsis patients at baseline (day 0) by receiver operating characteristic (ROC) and Kaplan-Meier curve analyses. Serum concentration of Angiotensinogen was more strongly associated with 30-day mortality than either the serum concentrations of renin or lactate in sepsis patients. Moreover, the clinical assessment of Angiotensinogen may have distinct advantages over the typical measures of renin. The assessment of intact Angiotensinogen may potentially facilitate more precise therapeutic approaches (including exogenous angiotensin II) to restore a dysfunctional RAS and improve patient outcomes. Additional prospective validation studies are clearly required for this biomarker in the future.

Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis.

BACKGROUND: Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting. This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction. METHODS: We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences. DISCUSSION: This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment. Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table. TRIAL REGISTRATION: PROSPERO registration: (CRD42024468883).

The Utility of C-Reactive Protein, Procalcitonin, and Leukocyte Values in Predicting the Prognosis of Patients with Pneumosepsis and Septic Shock.

Background and Objectives: The predictive value of changes in C-reactive protein (CRP), procalcitonin, and leukocyte levels, which are commonly used in the diagnosis of infection in sepsis and septic shock, remains a topic of debate. The aim of this study was to evaluate the effectiveness of changes in CRP, procalcitonin, and leukocyte counts on the prognosis of 230 patients admitted to the intensive care unit (ICU) with the diagnosis of sepsis and pneumonia-related septic shock between 1 April 2022 and 31 December 2023, and to investigate whether any of these markers have a superior predictive value over the others in forecasting prognosis. Materials and Methods: This single-center, retrospective, cross-sectional observational study included patients who developed sepsis and septic shock due to community-acquired pneumonia and were admitted to the ICU. Demographic data, 1-month and 90-day mortality rates, length of stay in the ICU, discharge to the ward or an outside facility, need for dialysis after sepsis, need for invasive or noninvasive mechanical ventilation during the ICU stay and the duration of this support, whether patients admitted with sepsis or septic shock required inotropic agent support during their stay in the ICU and whether they received monotherapy or combination therapy with antibiotics during their admission to the ICU, the Comorbidity Index score (CCIS), CURB-65 score (confusion, uremia, respiratory rate, BP, age ≥ 65), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) score were analyzed. Additionally, CRP, procalcitonin, and leukocyte levels were recorded, and univariate and multivariate logistic regression analyses were performed to evaluate their effects on 1- and 3-month mortality outcomes. In all statistical analyses, a p-value of <0.05 was accepted as a significant level. Results: According to multivariate logistic regression analysis, low BMI, male gender, and high CCIS, CURB-65, and APACHE-II scores were found to be significantly associated with both 1-month and 3-month mortality (p < 0.05). Although there was no significant relationship between the first-day levels of leukocytes, CRP, and PCT and mortality, their levels on the third day were observed to be at their highest in both the 1-month and 3-month mortality cases (p < 0.05). Additionally, a concurrent increase in any two or all three of CRP, PCT, and leukocyte values was found to be higher in patients with 3-month mortality compared with those who survived (p = 0.004). Conclusions: In patients with pneumoseptic or pneumonia-related septic shock, the persistent elevation and concurrent increase in PCT, CRP, and leukocyte values, along with male gender, advanced age, low BMI, and high CCIS, CURB-65, and APACHE-II scores, were found to be significantly associated with 3-month mortality.