Sepsis Biomarkers Research Articles

Circular RNA-Cacna1d Plays a Critical Role in Sepsis-induced Lung Injury by Sponging microRNA-185-5p.

The role of circular RNAs (circRNAs) in sepsis-induced lung injury is not clear. This study investigated the role and molecular mechanism of a novel circRNA in sepsis-induced lung injury and explored its prognostic value in patients with sepsis. In this study, aberrant circRNA expression profiling in lung tissues from mice with sepsis-induced lung injury was analyzed using high-throughput sequencing. circRNA-Cacna1d was verified by qRT-PCR, and its biological function in sepsis-induced lung injury was validated invitro and invivo. The interactions among circRNA-Cacna1d, microRNAs (miRNAs), and their downstream genes were verified. Furthermore, the clinical value of circRNA-Cacna1d in peripheral blood from patients with sepsis was also evaluated. We found that circRNA-Cacna1d expression was significantly increased in lung tissues of mice with sepsis and in microvascular endothelial cells after LPS challenge. circRNA-Cacna1d knockdown alleviated inflammatory response and ameliorated the permeability of vascular endothelium, thereby mitigating sepsis-induced lung injury and significantly improving the survival rate of mice with sepsis. Mechanistically, circRNA-Cacna1d directly interacted with miRNA-185-5p and functioned as a miRNA sponge to regulate the RhoA/ROCK1 signaling pathway. The expression level of circRNA-Cacna1d in patients with early sepsis was significantly higher than that in the healthy control subjects. Higher levels of circRNA-Cacna1d in patients with sepsis were associated with increased disease severity and poorer outcomes. In conclusions, circRNA-Cacna1d may play a role in sepsis-induced lung injury by regulating the RhoA/ROCK1 axis by acting as a miRNA-185-5p sponge. circRNA-Cacna1d is a potential therapeutic target for sepsis-induced lung injury and a prognostic biomarker in sepsis.

Antibody-free LC-HRMS/MS method for simultaneous quantification of NGAL, CRP and SAA in serum from sepsis patients.

Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS) is a valuable alternative to ligand-binding assay, enabling specific and accurate quantification of protein biomarkers. We developed a robust antibody-free LC-HRMS/MS method for the multiplex quantification of three sepsis biomarkers in serum: NGAL, CRP and SAA. The method was thoroughly optimized from sample preparation to LC-HRMS/MS analysis, alongside the calibration. Specifically, a modified trichloroacetic acid/isopropanol protein precipitation procedure combined with an optimized Parallel Reaction Monitoring acquisition allowed the quantification of the low abundant NGAL at ng/mL levels. While reference material and reference measurement procedure were available for CRP, no such standards existed for NGAL and SAA. Well-characterized peptide calibrators traceable to the international system of units were developed for NGAL and SAA. The method demonstrated suitable trueness and precision for the quantification of NGAL, CRP, and SAA with coefficients of variation (CV%) ranging from 1.6 % to 22.4 % and bias between -12.6 % and +18.0 %. Successful application to pooled serum samples illustrated the method's effectiveness. Our results pave the way toward the development of reference systems for additional sepsis biomarkers.

Resolvin D2 restores monocyte anisocytosis and mediates a shift toward classical monocytes exvivo in blood samples from patients after major burns.

Circulating monocytes contribute to the defense against pathogens and play a crucial role in maintaining immune homeostasis. While there is substantial evidence regarding the triggers of monocyte activation, our understanding of how monocyte function is restored toward homeostasis after activation remains limited. Here, we assessed the changes in monocyte anisocytosis upon activation in blood, measured by monocyte distribution width (MDW), a biomarker for sepsis. We determined that the increase in MDW post-lipopolysaccharide (LPS) stimulation in the blood can be reversed promptly by adding resolvin D2 (RvD2), and we measured a decrease in interleukin-1 beta (IL-1β) in blood, and a decrease in the size of the population of intermediate monocyte subsets. Moreover, the exvivo addition of RvD2 to blood samples from burn patients with high MDW restored normal MDW values. Further studies are needed to probe the potential therapeutic role of RvD2 in the context of burn injuries.

Identification of DNA damage repair-related genes in sepsis using bioinformatics and machine learning: An observational study.

Sepsis is a life-threatening disease with a high mortality rate, for which the pathogenetic mechanism still unclear. DNA damage repair (DDR) is essential for maintaining genome integrity. This study aimed to explore the role of DDR-related genes in the development of sepsis and further investigated their molecular subtypes to enrich potential diagnostic biomarkers. Two Gene Expression Omnibus datasets (GSE65682 and GSE95233) were implemented to investigate the underlying role of DDR-related genes in sepsis. Three machine learning algorithms were utilized to identify the optimal feature genes. The diagnostic value of the selected genes was evaluated using the receiver operating characteristic curves. A nomogram was built to assess the diagnostic ability of the selected genes via "rms" package. Consensus clustering was subsequently performed to identify the molecular subtypes for sepsis. Furthermore, CIBERSORT was used to evaluate the immune cell infiltration of samples. Three different expressed DDR-related genes (GADD45A, HMGB2, and RPS27L) were identified as sepsis biomarkers. Receiver operating characteristic curves revealed that all 3 genes showed good diagnostic value. The nomogram including these 3 genes also exhibited good diagnostic efficiency. A notable difference in the immune microenvironment landscape was discovered between sepsis patients and healthy controls. Furthermore, all 3 genes were significantly associated with various immune cells. Our findings identify potential new diagnostic markers for sepsis that shed light on novel pathogenetic mechanism of sepsis and, therefore, may offer opportunities for potential intervention and treatment strategies.

A Dual-Pipeline Lactate Removal Strategy to Reverse Vascular Hyperpermeability for the Management of Lipopolysaccharide-Induced Sepsis.

Sepsis is an underappreciated yet severe threat to human life, marked by organ dysfunction and high mortality resulting from disordered inflammatory responses to blood infection. Unfortunately, no specific drugs are available for effective sepsis treatment. As a pivotal biomarker for sepsis, lactate levels are closely related to vascular permeability and sepsis-associated mortality. Herein, a dual-pipeline lactate removal strategy is reported from circulating blood to ameliorate vascular permeability and lipopolysaccharide (LPS)-induced sepsis. This is achieved by formulating lactate oxidase (LOX)-encapsulated hollow manganese dioxide (HMnO2) nanohybrids (LOX@HMnO2-P[5]A) bearing pillar[5]arene (P[5]A) macrocycle with excellent host-guest properties. The highly biocompatible nanohybrids enable direct lactate consumption through LOX catalytic degradation and block lactate production by P[5]A-mediated LPS trapping, allowing for dual-pipeline lactate removal to maximize the reversal of lactate-mediated vascular hyperpermeability. Besides, HMnO2 cores decompose hydrogen peroxide produced from lactate oxidation into oxygen, further contributing to lactate consumption and mitigating the hypoxic inflammatory environment. In vivo investigations demonstrate that intravenous administration of LOX@HMnO2-P[5]A nanohybrids with extended blood circulation can effectively ameliorate endothelial barrier dysfunction, inflammatory responses, and multiple organ injury, ultimately improving survival outcomes in LPS-induced sepsis. Taken together, this dual-pipeline lactate removal strategy offers a promising approach for efficient sepsis treatment.

A systematic review on the influence of coagulopathy and immune activation on New Onset Atrial Fibrillation in patients with sepsis.

New Onset Atrial Fibrillation (NOAF) is the most common arrhythmia in intensive care. Complications of NOAF include thromboembolic events such as myocardial infarction and stroke, which contribute to a greater risk of mortality. Inflammatory and coagulation biomarkers in sepsis are thought to be associated with NOAF development. The aim of this systematic review and narrative synthesis is to identify inflammatory and coagulation biomarkers as predisposing risk factors for NOAF in sepsis. Three databases (Medline, Cochrane Library, and Scopus) were searched using a predefined search strategy. Inclusion / exclusion criteria were applied, and quality assessments were performed using the Newcastle Ottawa Scale (NOS). We identified 1776 articles; and 12 articles were included in this review. 8 articles were retrospective observational studies and 4 were prospective observational studies. There was considerable heterogeneity between studies regarding outcomes, methodological design, quality, definitions and reported biomarkers of interest. There is evidence that C-reactive protein (CRP) is associated with NOAF, with hazard ratios 3.33 (3.32-3.35) p = 0.001 and odds ratios of 1.011 (1.008-1.014) p<0.001. International Normalised Ratio (INR) and fibrinogen may be associated with NOAF with odds ratios reported as 1.837 (1.270-2.656) p = 0.001 and 1.535(1.232-1.914) p<0.001 respectively. Further research is required to confirm the association between inflammatory and coagulation biomarkers and the development of NOAF in sepsis. A broader evidence base will guide treatment strategies, improving the standard of care for patients who develop NOAF in sepsis. Furthermore, given the heterogeneity between studies consideration should be given to inclusion of immune biomarkers in future core outcome sets for trials investigating NOAF.

P-76 UNEXPECTED RAISE OF PROCALCITONIN IN PATIENT WITH TREATED FOR DF INFECTION REVEALED MEDULLARY THYROID CANCER

Abstract Introduction To demonstrate the importance of differential diagnosis of rare causes of procalcitonin (PCT) elevation. Materials-Methods Case of patient with diabetic foot infection, knee joint injury, and persistent elevation of PCT level on antibiotic therapy. Results PCT and C-reactive protein (CRP) are biomarkers of sepsis. Raised PCT and CRP after antibacterial therapy (ABT) can be associated with different factors. Reviewed publications suggest the following causes of elevated PCT: ketoacidosis, liver diseases, acute kidney injury, trauma, burns, calcitonin-secreting neuroendocrine tumors, medullary thyroid cancer (MTC). Clinical Case 70-year-old woman with type 2 diabetes mellitus was admitted for closed fracture of the right patella. Persistent wound of the right foot after a forefoot amputation in 2022, dry necrosis of the 4th toe of the left foot was found. Tests detected: PCT - 7.3 ng/mL (0-0.5), CRP - 156 mg/L (0.0-5.0). ABT and local wound care were initiated. A left lower limb revascularization and a 4th left toe disarticulation were performed. In 5 days open reduction and osteosynthesis of the right patella were performed. After 2 weeks of ABT there were no signs of wound infection, CRP level decreased but PCT was still high, 5.7 ng/mL (0-0.5). One of the hypotheses was that the raised PСT was not related to infection. The patient had previously had a multinodular goiter so the calcitonin level was checked (above 950 pg/mL). Thyroid biopsy detected medullary carcinoma (MTC). Later total thyroidectomy and central neck dissection were performed. Histology: medullary thyroid carcinoma (MTC) (pT2N0(0/2), Lv0, Pn0, R0). No pathogenic or probably pathogenic mutations were found. In 1 month, calcitonin was 3.7 pg/mL. Conclusion Causes of elevated procalcitonin (PCT) may be not related to infections, which is an important finding for physicians treating comorbid diabetic patients with infection. This case underscores the role of PCT in the diagnosis of MTC. While the current findings highlight its utility in clinical practice, further studies are needed to explore full potential and establish standardised guidelines for use PCT in MTC management.

Epigenome-wide DNA methylation profiling in septic and non-septic patients with similar infections: potential use as sepsis biomarkers

IntroductionSepsis is a life-threatening condition caused by a dysregulated immune response to infection, leading to organ failure. Despite its significant global burden, the underlying mechanisms of immune dysfunction in sepsis remain incompletely understood. This study explores the role of DNA methylation in white blood cells in sepsis pathogenesis.MethodsA prospective case-control study was conducted to compare DNA methylation profiles between patients with community-acquired sepsis and matched controls who had similar infections but did not develop sepsis. Whole blood samples from these patients were analyzed using the Infinium MethylationEPIC v2.0 kit, enabling genome-wide methylation analysis. Selected genes with differential methylation were validated by pyrosequencing.ResultsSignificant differential DNA methylation patterns were identified between septic and non-septic individuals uising. Our results suggest that DNA methylation changes are closely linked to the pathophysiological processes of sepsis, influencing immune cell activation, inflammation, and organ dysfunction. The most prominent findings include the hypomethylation of immune-related genes (SERPINA1, AZU1, MPO, and SLX4), which were strongly correlated with clinical severity and inflammatory markers such as SOFA scores and PCT levels. Correlation analyses demonstrated significant associations between the methylation levels of these genes and clinical severity markers, such as SOFA score and PCT levels. Notably, SLX4 hypomethylation showed the highest predictive value for poor prognosis (AUC 0.821), while SERPINA1 hypomethylation exhibited strong diagnostic potential for sepsis (AUC 0.858).DiscussionOur results underscore the potential of DNA methylation changes, particularly in immune-related genes, to enhance the early detection of sepsis and to stratify patients based on severity. Future research should explore the therapeutic implications of these epigenetic alterations in sepsis care.

Pathogenetic and prognostic aspects of copper and zinc deficiency in severely burned patients

Objective. To study the copper and zinc content in the severely burned patients’ blood serum and evaluate their capabilities as prognostic criteria for the burn disease outcome.Materials and methods. 37 patients with a burn area of 50,7±17,2 % of the body surface were examined, 7 of them died. The content of copper, zinc, albumin, globulins and prealbumin in blood serum was assessed within 14 days after receiving thermal injury.Results. A copper and zinc deficiency was found during the burn shock. In the future, the copper levels normalization and a tendency to the zinc concentration increase with normalization by 14 days after burn injury are noted. The micronutrient deficiency correlation with the albumin, prealbumin and globulins levels was found. The conjugacy between hypocyncemia and hypocupremia with the sepsis presence and the death probability was revealed. A decrease in zinc levels below 4,7 mmol/l leads to a 24-fold increase in the death chances and in copper content below 13 mmol/l – to a 10–fold increase in the chances. The sensitivity and specificity of the zinc concentration threshold value assessment was 71 % and 90 %, respectively, and the copper concentration was 80 % and 75 % respectively.Conclusion. During the burn shock hypocupremia and hypocyncemia are detected. Further normalization of the copper level and a tendency to zinc concentration normalization were revealed. Zinc and copper concentrations can serve as additional sepsis biomarkers. Threshold values of zinc and copper concentrations in blood serum have been determined which determine the fatal outcome risk of burn disease.

LncRNA FENDRR/ miR-424-5p serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes.

This study intends to investigate the relationship between FENDRR and miR-424-5p and their clinical significance in sepsis, aiming to provide new diagnostic markers and prognostic markers for sepsis. 136 patients with sepsis and 132 healthy volunteers were included as study subjects. The expression levels of FENDRR and miR-424-5p were detected by qPCR. ROC was applied to evaluate the diagnostic value of FENDRR and miR-424-5p. COX analyzed the independent risk factors for the occurrence of death in sepsis patients. Dual luciferase reporter assay detected the binding of FENDRR and miR-424-5p. The miR-424-5p target genes were predicted and enriched for GO function and KEGG pathway. FENDRR was up-regulated and miR-424-5p was down-regulated in patients with sepsis. FENDRR can target and bind to miR-424-5p. Both FENDRR and miR-424-5p showed significant diagnostic potential in sepsis and their combination significantly improved the diagnostic efficiency. FENDRR/miR-424-5p were significantly correlated with WBC, CRP, APACH II, and SOFA of sepsis patients. FENDRR and miR-424-5p were independent risk factors for mortality in sepsis patients. Sepsis patients with high FENDRR levels or low miR-424-5p levels had higher mortality. GO and KEGG enrichment analyses revealed that the targets of miR-424-5p were predominantly associated with cell functions and inflammatory signaling pathways. Upregulated FENDRR and downregulated miR-424-5p expression can serve as biomarkers of sepsis with predictive value on the onset and prognostic outcome. FENDRR and miR-424-5p were correlated with the severity of sepsis and FENDRR can play a function in the sepsis progression via targeting miR-424-5p.

Potentials of Presepsin as a Novel Sepsis Biomarker in Critically Ill Adults: Correlation Analysis with the Current Diagnostic Markers.

Background: Sepsis is a major cause of patient death in intensive care units (ICUs). Rapid diagnosis of sepsis assists in optimizing treatments and improves outcomes. Several biomarkers are employed to aid in the diagnosis, prognostication, severity grading, and sub-type discrimination of severe septic infections (SSIs), including current diagnostic parameters, hemostatic measures, and specific organ dysfunction markers. Methods: This study involved 129 critically ill adults categorized into three groups: sepsis (Se = 48), pneumonia (Pn = 48), and Se/Pn (33). Concentrations of five plasma markers (IL-6, IL-8, TREM1, uPAR, and presepsin) were compared with 13 well-established measures of SSI in critically ill patients. These measures were heart rate (HR), white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), lactate plasma concentrations, and measures of hemostasis status (platelets count (PLT), fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalization ratio (INR) and D-dimer). Plasma bilirubin and creatinine served as indicators of liver and kidney dysfunction, respectively. Results: Promising roles for these biomarkers were found. The best results were for presepsin, which scored 10/13, followed by IL-6 and IL-8 (each scored 7/13), and the worst were for TREM-1 and uPAR (scored 3/13). Presepsin, IL-6, and IL-8 discriminated between the SSI sub-types, whilst only presepsin correlated with bilirubin and creatinine. uPAR was positive for kidney dysfunction, and TREM-1 was the only indicator of artificial ventilation (AV). Conclusions: Presepsin is an important potential biomarker in SSIs. However, further work is needed to define this marker's diagnostic and prognostic cutoff values.

Sex differences in the time trends of sepsis biomarkers following polytrauma

Sepsis is a major cause of death in polytrauma patients, with delayed antibiotics increasing mortality. Although biological sex influences immune function and disease outcomes, gender-specific differences in inflammatory response and sepsis progression remain underexplored. This study examined the time-dependent behavior of C-reactive protein (CRP), procalcitonin (PCT), and white blood cell count (WBC) in male and female polytrauma patients to evaluate their predictive value for sepsis. Additionally, it compared infection sources between genders. This retrospective cohort study at University Hospital Zurich included polytrauma patients aged ≥ 16 years with an Injury Severity Score (ISS) ≥ 16 who developed sepsis within 31 days of admission. Patients were grouped by sepsis status and gender. Time-dependent inflammatory markers (CRP, PCT, WBC) were analyzed using the Mann–Whitney U-test and binary logistic regression. The Closest Top-Left Threshold Method determined time-specific sepsis thresholds. The study included 3059 polytrauma patients (26% females, 74% males), with a median age of 43 and a median ISS of 27. CRP levels were higher in sepsis cases from 24 h in females and 48 h in males, peaking at 122.5 mmol/L (females, 4 days) and 136.5 mmol/L (males, 48 h). PCT differences were significant only in males from 12 h, with a threshold of 1.55 µg/L. WBC levels became significant from day 3 in males and day 4 in females, peaking at 12.82 counts/µL (males) and 13.16 counts/µL (females) on day 10. Pneumonia was the most common infection (70% males, 65% females). Females had more wound infections (27% vs. 18%, p = 0.042) and borderline higher urinary tract infections (22% vs. 14%, p = 0.059). CRP and PCT are standard sepsis markers, but PCT’s predictive value varies by gender, and women may show different CRP kinetics. Gender-specific differences in inflammatory markers suggest tailored approaches to enhance diagnostic accuracy and improve sepsis management. Further research is needed to evaluate hormonal and genetic influences on immune responses in polytrauma patients.

Advances and Challenges in Pediatric Sepsis Diagnosis: Integrating Early Warning Scores and Biomarkers for Improved Prognosis.

Identifying and managing pediatric sepsis is a major research focus, yet early detection and risk assessment remain challenging. In its early stages, sepsis symptoms often mimic those of mild infections or chronic conditions, complicating timely diagnosis. Although various early warning scores exist, their effectiveness is limited, particularly in prehospital settings where accurate, rapid assessment is crucial. This review examines the roles of clinical prediction tools and biomarkers in pediatric sepsis. Traditional biomarkers, like procalcitonin (PCT), have improved diagnostic accuracy but are insufficient alone, often resulting in overprescription of antibiotics or delayed treatment. Combining multiple biomarkers has shown promise for early screening, though this approach can be resource-intensive and less feasible outside hospitals. Predicting sepsis outcomes to tailor therapy remains underexplored. While serial measurements of traditional biomarkers offer some prognostic insight, their reliability is limited, with therapeutic decisions often relying on clinical judgment. Novel biomarkers, particularly those identifying early organ dysfunction, hold potential for improved prognostic accuracy, but significant barriers remain. Many are only available in hospitals, require further validation, or need specialized assays not commonly available, limiting broader clinical use. Further research is needed to establish reliable protocols and enhance the clinical applicability of these tools. Meanwhile, a multifaceted approach that combines clinical judgment with existing tools and biomarkers remains essential to optimize pediatric sepsis management, improving outcomes and minimizing risks.

Genetic analysis of diagnostic and therapeutic potential for ferroptosis in postoperative sepsis.

Ferroptosis is a new form of iron-dependent cell death that is closely associated with sepsis. However, few studies have investigated the diagnostic and therapeutic potential for ferroptosis-related genes (FRGs) among postoperative sepsis. The GSE131761 dataset was used to identify differentially expressed FRGs (DE-FRGs). KEGG and GO analyses were subsequently performed. LASSO and SVM-RFE methods were applied for identifying genetic biomarkers for sepsis. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were applied for exploring the biological properties of the DEGs. CIBERSORT was applied to analyse immune cell infiltration. DGldb was employed for predicting potential target drugs for the DEGs. Competing endogenous RNA (ceRNA) networks were constructed to analyse the regulatory patterns of the DEGs. The expression of hub genes was validated based on GSE26440 dataset. The bioinformatics analysis was carried out with R software (version 4.1.2). Blood from sepsis patients and healthy controls was collected and the expression of hub genes was experimentally verified by real-time quantitative polymerase chain reaction (RT-qPCR). 38 sepsis-associated DE-FRGs were assessed via Gene Expression Omnibus (GEO) and Ferroptosis database (FerrDb), and the gene function analysis showed that they were closely related to inflammatory response and autophagy regulation. Subsequently, SVM-RFE and LASSO methods determined 7 marker genes. GSEA suggested that these marker genes may be involved in regulating several biological pathways. Furthermore, 52 gene-targeted drugs were identified in this study, the vast majority of which were associated with MAPK14. CIBERSORT analysis suggested that SLC38A1, MGST1, and MAPK14 may be involved in immune microenvironment alterations. We revealed the potential complex regulatory relationship by constructing a ceRNA network based on marker genes. Finally, 6 genes were validated in the validation set, with 5 of them further confirmed through RT-qPCR. Seven genes associated with ferroptosis are screened from postoperative sepsis samples. The expression of these genes has high diagnostic validity for sepsis and may serve as potential diagnostic biomarkers. This study gives an entrance point to uncover the underlying mechanisms of sepsis.

Preliminary screening of new biomarkers for sepsis using bioinformatics and experimental validation.

The morbidity and mortality of sepsis remain high, and so far specific diagnostic and therapeutic means are lacking. To screen novel biomarkers for sepsis. Raw sepsis data were downloaded from the Chinese National Genebank (CNGBdb) and screened for differentially expressed RNAs. Key genes with predictive value were identified through weighted correlation network analysis (WGCNA) and meta-analysis and survival analysis using multiple public databases. Core genes were analyzed for functional enrichment using Gene Set Enrichment Analysis(GSEA). The core genes were localized using single-cell sequencing. qPCR was used to validate the core genes. Differential analysis yielded a total of 5125 mRNA. WGCNA identified 5 modules and screened 3 core genes (S100A11, QPCT, and IFITM2). The prognosis of sepsis patients was strongly linked to S100A11, QPCT, and IFITM2 based on meta-analysis and survival analysis(P < 0.05).GSEA analysis showed that S100A11, QPCT, and IFITM2 were significantly enriched in ribosome-related pathways. S100A11 and QPCT were widely distributed in all immune cells, and QPCT was mainly localized in the macrophage cell lineage. In the sepsis group, the qPCR results showed that S100A11, QPCT, and IFITM2 expression levels were significantly higher in the sepsis group(P < 0.05). In this study, S100A11, QPCT, and IFITM2 were screened as new potential biomarkers for sepsis. Validated by bioinformatics analysis and qPCR, these genes are closely associated with the prognosis of sepsis patients and have potential as diagnostic and therapeutic targets.

Biomarkers of sepsis in burn injury: an update.

Sepsis, a dysregulated response to infection, is a leading cause of death after burn injury. Changes in the immune response as well as the loss of the skin, the primary barrier to infection, contribute to the increased risk for infection and sepsis in burn patients. This higher risk is further compounded by the development of the systemic inflammatory response and hypermetabolic state, which limit the utility of commonly used infection markers. As such, the development of sepsis biomarkers after burn injury is an imperative. A sepsis biomarker would facilitate earlier diagnosis and treatment of sepsis, thus decreasing length of stay, morbidity, and mortality after burn injury. Numerous different biomarkers, ranging from acute phase reactants, cytokines, and inflammatory markers to omics analyses and extracellular vesicles have been assessed as potential biomarkers in burn sepsis. To date no single biomarker has proven useful as the sole indicator for sepsis. The future of burn sepsis biomarkers will likely require a panel of biomarkers from all categories. The purpose of this review article is to list the various biomarkers that have been studied in burn sepsis and describe their clinical utility and future use in patients with burn injury.

Pancreatic Stone Protein as Sepsis Biomarker in Patients Requiring Mechanical Circulatory Support: a Pilot Observational Study

Pancreatic Stone Protein as Sepsis Biomarker in Patients Requiring Mechanical Circulatory Support: a Pilot Observational Study

Impact of different pathogen classes on the serum N-glycome in septic shock.

The morbidity and mortality of sepsis remain high. Clinicians lack effective markers to rapidly diagnose sepsis and identify the underlying pathogen infection particularly for patients with candidaemia or cases of culture-negative sepsis where culture-based diagnostics are inadequate. In our search for new lines of potential sepsis biomarkers, we here explore the impact of various classes of infectious agents on the serum N-glycome in a septic shock cohort. Comparative N-glycomics was performed on sera collected from 49 septic shock patients infected with viral (n = 9), bacterial (n = 37) or fungal (n = 3) pathogens using an established PGC-LC-MS/MS method. Aberrant serum N-glycosylation features were observed in patients with fungal infection relative to the other infection sub-groups including i) altered expression of prominent α2,6-sialylated biantennary N-glycan isomers, ii) elevated levels of IgG-type N-glycosylation and iii) a global shift in the serum N-glycome involving altered glycan type distribution and considerable changes in core fucosylation and α2,6-sialylation. Septic shock patients infected with bacterial and viral pathogens exhibited similar global serum N-glycome features and therefore could not be stratified based on their serum N-glycosylation. Subtle and less consistent serum N-glycome differences were observed between septic shock patients infected with different bacterial pathogens. In conclusion, our study has tested the impact of different pathogen classes on the serum N-glycome in a septic shock cohort, and reports that fungal infection impacts the host serum N-glycome differently compared to bacterial or viral infections thus potentially opening avenues for glycan-based biomarkers to better diagnose patients with candidaemia.

The Need for Standardized Guidelines for the Use of Monocyte Distribution Width (MDW) in the Early Diagnosis of Sepsis.

Sepsis is a complex and potentially life-threatening syndrome characterized by an abnormal immune response to an infection, which can lead to organ dysfunction, septic shock, and death. Early diagnosis is crucial to improving prognosis and reducing hospital management costs. This narrative review aims to summarize and evaluate the current literature on the role of monocyte distribution width (MDW) as a diagnostic biomarker for sepsis, highlighting its advantages, limitations, and potential clinical applications. MDW measures the volumetric distribution width of monocytes, reflecting monocytic anisocytosis, and is detected using advanced hematological analyzers. In 2019, it was approved by the FDA as a biomarker for sepsis due to its ability to identify systemic inflammatory response at an early stage. Thirty-one studies analyzed by us have shown that an increased MDW value is associated with a higher risk of sepsis and that its combination with clinical parameters (such as qSOFA) and other biomarkers (CRP, PCT) can enhance diagnostic sensitivity and risk stratification capacity. Despite its high sensitivity, MDW has lower specificity compared to more established biomarkers such as procalcitonin, thus requiring a multimodal integration for an accurate diagnosis. The use of MDW in emergency and intensive care settings represents an opportunity to improve early sepsis diagnosis and critical patient management, particularly when combined with other markers and clinical tools. However, further studies are needed to define a universal cut-off and confirm its validity in different clinical contexts and pathological scenarios.

Identification of amino acid metabolism‑related genes as diagnostic and prognostic biomarkers in sepsis through machine learning.

Previous research has highlighted the critical role of amino acid metabolism (AAM) in the pathophysiology of sepsis. The present study aimed to explore the potential diagnostic and prognostic value of AAM-related genes (AAMGs) in sepsis, as well as their underlying molecular mechanisms. Gene expression profiles from the Gene Expression Omnibus (GSE65682, GSE185263 and GSE154918 datasets) were analyzed. Based on weighted gene co-expression network analysis and machine learning algorithms, hub AAMGs were identified in the GSE65682 database. Subsequently, hub AAMGs were evaluated for their expression levels and diagnostic and prognostic significance in sepsis, as well as their interactions with regulatory pathways and role in immune cell infiltration. Additionally, trends in AAMG expression were validated using clinical samples, and their functions in sepsis were confirmed through an in vitro model. In total, four AAMGs were identified, two of which, methionine synthase (MTR) and methionine-R-isomerase 1 (MRI1), demonstrated significant differential expression in the GSE65682, GSE185263 and GSE154918 datasets, which was further validated using clinical samples. A diagnostic nomogram based on MTR and MRI1 expression demonstrated strong diagnostic effectiveness across the three aforementioned databases. Moreover, the expression of both genes were negatively correlated with sepsis prognosis and showed stratified prognostic capabilities. Newly identified pathways included KRAS and IL-2/STAT5 signaling. MTR and MRI1 negatively correlated with the infiltration of inflammatory cells, such as M1 macrophages and neutrophils, and positively correlated with anti-inflammatory cells, such as CD8+ T and dendritic cells. In vitro experiments further demonstrated that overexpression of MTR could mitigate the inhibition of cloning and proliferation induced by LPS and ATP in RAW 264.7 cells. These findings highlighted the potential of MTR and MRI1 as biomarkers for diagnosing and prognosticating sepsis, potentially acting through the regulation of methionine in the pathophysiology of this disease. The present study provided new insights into the role of AAM in the mechanisms underlying sepsis and in the potential development of future targeted therapies.