Sepsis Biomarkers Research Articles

CD4 + T cells ferroptosis is associated with the development of sepsis in severe polytrauma patients

BackgroundImmunological disorder remains a great challenge in severe poly-trauma, in which lymphopenia is an important contributor. The purpose of present study is to explore whether ferroptosis, a new manner of programmed cell death (PCD), is involved in the lymphocyte depletion and predictive to the adverse prognosis of severe injuries. Patients and MethodsSevere polytrauma patients admitted from January 2022 to December 2022 in our trauma center were prospectively investigated. Peripheral blood samples were collected at admission (day 1), day 3 and day 7 from them. Included patients were classified based on whether they developed sepsis or not. Clinical outcomes, systematic inflammatory response, lymphocyte subpopulation, CD4 + T cell ferroptosis were collected, detected and analyzed. ResultsNotable lymphopenia was observed on the first day after severe trauma and failed to normalize on the 7th day if patients were complicated with sepsis, in which CD4 + T cell was the subset of lymphocyte that depleted most pronouncedly. Lymphocyte loss was significantly correlated with the acute and biphasic systemic inflammatory response. Ferroptosis participated in the death of CD4 + T cells, potentially mediated by the downregulation of xCT-GSH-GPX4 pathway. CD4 + T cells ferroptosis had a conducive predicting value for the development of sepsis following severe trauma. ConclusionsCD4 + T cells ferroptosis occurs early in the acute stage of severe polytrauma, which may become a promising biomarker and therapeutic target for post-traumatic sepsis.

A prospective cohort study of severe sepsis-induced dyslipidemia and changes in D-dimer levels in children: do they affect the prognosis?

BackgroundThe dyslipidemia and changes in D-dimer values that occur in children with severe sepsis remain unidentified.ObjectiveThe current research aimed to explore the relationship between D-dimer and lipid profile values, including total cholesterol (TC), lipoproteins, apolipoprotein A-V (Apo A-5), triglycerides (TG), and in-hospital nonsurvival in children with severe sepsis or septic shock in pediatric intensive care.Study designThe study design is as follows: prospective cohort study.ParticipantsChildren with severe sepsis or septic shock who were admitted to the intensive care unit of a university pediatric hospital.InterventionVital signs, sepsis assessment, pediatric sequential organ failure assessment (PSOFA) score, high-density lipoprotein (HDL), Apo A-5, TG, low-density lipoprotein (LDL), TC, D-dimer, mortality outcome, and pediatric risk of mortality (PRISM) III score were evaluated.OutcomesThe primary outcome was in-hospital nonsurvival.ResultsThe nonsurvivors had significantly higher D-dimer levels than the survivors, with a significant cutoff level of 0.87 μg/mL (AUC: 0.85, sensitivity: 93.3%, PVN: 90.6%, accuracy: 79.0%, PVP: 72.5%, and specificity: 64.7%). D-dimer was inversely correlated with WBC count and positively correlated with patient age, PRISM III score, PSOFA score, and INR. However, nonsurvivors had higher TG levels and lower TC, HDL, LDL, and Apo A-5 levels than survivors, but this variation was insignificant. Apo A-5 levels were inversely correlated with HDL and positively correlated with TG levels.ConclusionsThis study suggests that D-dimer is a promising biomarker for severe sepsis in children, with a mortality cutoff level of 0.87 μg/mL. However, lipid profiles are not predictors of sepsis-related mortality.

Utility of heparin-binding protein following cardiothoracic surgery using cardiopulmonary bypass

Cardiothoracic surgery using cardiopulmonary bypass (CPB) triggers an inflammatory state that may be difficult to differentiate from infection. Heparin-binding protein (HBP) is a candidate biomarker for sepsis. As data indicates that HBP normalizes rapidly after cardiothoracic surgery, it may be a suitable early marker of postoperative infection. We therefore aimed to investigate which variables influence postoperative HBP levels and whether elevated HBP concentration is associated with poor surgical outcome. This exploratory, prospective, observational study enrolled 1475 patients undergoing cardiothoracic surgery using CPB, where HBP was measured at ICU arrival. Patients with HBP in the highest tercile were compared to remaining patients. Multivariable logistic regressions were performed to identify factors predictive of elevated HBP and 30-day mortality. Overall median HBP was 30.0 ng/mL. Patients undergoing isolated CABG or surgery with CPB-duration ≤ 60 min had a median HBP of 24.9 ng/mL and 23.2 ng/mL, respectively. Independent predictors of elevated postoperative HBP included increased EuroSCORE, prolonged CPB-duration and high intraoperative temperature. Increased HBP was an independent predictor of 30-day mortality. This study confirms the promising characteristics of HBP as a biomarker for identification of postoperative sepsis, especially after routine procedures. Further studies are required to investigate whether HBP may detect postoperative infections.

Variation in presepsin and thrombomodulin levels for predicting COVID-19 mortality

Coronavirus disease (COVID-19) has caused extensive mortality globally; therefore, biomarkers predicting the severity and prognosis of COVID-19 are essential. This study aimed to evaluate the application of presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively, in the prognosis of COVID-19. Serum P-SEP and TM levels from COVID-19 patients (n = 183) were measured. Disease severity was classified as mild, moderate I, moderate II, or severe based on hemoglobin oxygen saturation and the history of intensive care unit transfer or use of ventilation at admission. Patients in the severe group were further divided into survivors and non-survivors. P-SEP and TM levels were significantly higher in the severe group than those in the mild group, even after adjusting for creatinine values. In addition, TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points with an interval of 4.1 ± 2.2 days were significantly different between the survivors and non-survivors. In conclusion, TM and continuous P-SEP measurements may be useful for predicting mortality in patients with COVID-19. Moreover, our data indicate that P-SEP and TM values after creatinine adjustment could be independent predictive markers, apart from renal function.

Removal characteristics of presepsin by operating conditions and hemofilter.

Presepsin, which is used as a biomarker for sepsis, is thought to be removed by dialysis, but the actual removal properties of dialysis are unknown. We investigated the presepsin removal properties of continuous hemodiafiltration using the high concentration of presepsin from human plasma drained by plasma exchange. Each solution in plasma exchange was connected to a continuous hemodiafiltration blood circuit and circulated at 4 conditions. The results show that presepsin was confirmed to be removed more efficiently in hemofiltration than in hemodialysis. In addition, when using a polymethylmethacrylate hemofilter for continuous hemodiafiltration, the lowest presepsin concentration is on the filtrate side, suggesting that the main removal mechanism is adsorption. Since presepsin has a molecular weight of 13,000, its removal efficiency is high by hemofiltration as per principle. In addition, since the main adsorption principle of polymethylmethacrylate hemofilter is hydrophobic bond, presepsin is considered to be adsorbed. Since presepsin is metabolized in the kidney, it is elevated in renal failure. In this paper, we confirmed that presepsin is eliminated by continuous hemodiafiltration not only in the kidney. Depending on the timing of presepsin measurement, there is a risk of missing the diagnosis of sepsis. Kidney function and continuous hemodiafiltration should be checked when measuring presepsin.

Bioinformatics reveals diagnostic potential of cuproptosis-related genes in the pathogenesis of sepsis

BackgroundMultiple modes of cell death occur during the development of sepsis. Among these patterns, cuproptosis has recently been identified as a regulated form of cell death. However, its impact on the onset and progression of sepsis remains unclear. MethodWe screened a dataset of gene expression profiles from patients with sepsis using the GEO database. Survival analysis was performed to analyze the relationship between cuproptosis-related genes (CRGs) and prognosis. Hub genes were identified through univariate Cox regression analysis. The diagnostic value of hub genes in sepsis was tested in both training sets (GSE65682) and validation sets (GSE134347). To examine the association between hub genes and immune cells, single-sample gene set enrichment analysis (ssGSEA) and Pearson correlation analysis were employed. Additionally, the CRGs were validated in a septic mouse model using real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC). ResultsIn sepsis, most CRGs were upregulated, with only DLD and MTF1 downregulated. High expression of three genes (GLE, LIAS, and PDHB) was associated with better prognosis, but only two hub genes (LIAS, PDHB) reached statistical significance. The receiver operating characteristic (ROC) analysis for diagnosing sepsis showed LIAS had a range of 0.793–0.906, while PDHB achieved values of 0.882 and 0.975 in the training and validation sets, respectively. ssGSEA analysis revealed a lower number of immune cells in the sepsis group, and there was a correlation between immune cell population and CRGs (LIAS, PDHB). Analysis in the septic mouse model demonstrated no significant difference in mRNA expression levels and IHC staining between LIAS and PDHB in heart and liver tissues, but up-regulation was observed in lung tissues. Furthermore, the mRNA expression levels and IHC staining of LIAS and PDHB were down-regulated in renal tissues. ConclusionsCuproptosis is emerging as a significant factor in the development of sepsis. LIAS and PDHB, identified as potential diagnostic biomarkers for cuproptosis-associated sepsis, are believed to play crucial roles in the initiation and progression of cuproptosis-induced sepsis.

µPAD-based colorimetric nanogold aptasensor for CRP and IL-6 detection as sepsis biomarkers

Point-of-care testing is defined as medical diagnostic testing at or near the time and place of a patient. The integration of microfluidics with functionalized nanomaterials provides a rapid and sensitive detection method for biomarkers. Due to their optical characteristics, gold nanoparticles (GNPs) and aptamers can be used in a colorimetric technique. In this research, accurate and quick aptasensors were created using aptamers for two sepsis biomarkers, interleukin-6 (IL-6) and C-reactive protein (CRP). Aptamers were combined with GNPs to create aptasensors, which were then used to analyze various biomarker concentrations after aptamer-protein docking on the online HDOCK server to verify aptamer-protein interactions. To improve the results' stability and ease of use during the reaction time, microfluidic paper-based analytical devices (µPAD) was employed. The linear diagnostic ranges in this method were 50–1000 mg L−1 and 1–25 ng/L, and limit of detection values were 1.9 mg L−1 and 0.07 ng/L for CRP and IL-6, respectively; These values decreased when µPADs were used and became more suitable to diagnosis of sepsis. Two aptasensors were highly stable, reproducible, accurate, and recoverable. Our result suggests that colorimetric GNPs can be used to detect a specific analyte through color changes visible to the naked eye for monitoring purposes or as simple optical detectors for quantitative measurements.

Uncovering hub genes in sepsis through bioinformatics analysis.

In-depth studies on the mechanisms of pathogenesis of sepsis and diagnostic biomarkers in the early stages may be the key to developing individualized and effective treatment strategies. This study aimed to identify sepsis-related hub genes and evaluate their diagnostic reliability. The gene expression profiles of GSE4607 and GSE131761 were obtained from the Gene Expression Omnibus. Differentially co-expressed genes between the sepsis and control groups were screened. Single-sample gene set enrichment analysis and gene set variation analysis were performed to investigate the biological functions of the hub genes. A receiver operating characteristic curve was used to evaluate diagnostic value. Datasets GSE154918 and GSE185263 were used as external validation datasets to verify the reliability of the hub genes. Four differentially co-expressed genes, FAM89A, FFAR3, G0S2, and FGF13, were extracted using a weighted gene co-expression network analysis and differential gene expression analysis methods. These 4 genes were upregulated in the sepsis group and were distinct from those in the controls. Moreover, the receiver operating characteristic curves of the 4 genes exhibited considerable diagnostic value in discriminating septic blood samples from those of the non-septic control group. The reliability and consistency of these 4 genes were externally validated. Single-sample gene set enrichment analysis and gene set variation analysis analyses indicated that the 4 hub genes were significantly correlated with the regulation of immunity and metabolism in sepsis. The identified FAM89A, FFAR3, G0S2, and FGF13 genes may help elucidate the molecular mechanisms underlying sepsis and drive the introduction of new biomarkers to advance diagnosis and treatment.

Identification of novel immune infiltration-related biomarkers of sepsis based on bioinformatics analysis

Identification of novel immune infiltration-related biomarkers of sepsis based on bioinformatics analysis

The relationship between platelet to lymphocyte ratio with neonatal sepsis at Wangaya General Hospital

Background: Neonatal sepsis is still a major health problem throughout the world and one of the leading causes of morbidity and mortality in neonates. This disease often goes undetected and causes death. The diagnosis and treatment of neonatal sepsis is still a problem today. According to current research, the platelet-to-lymphocyte ratio (PLR) plays a significant role in the inflammatory process. This study aims to contribute to the research on whether PLR is connected with the incidence of neonatal sepsis and can be used as a biomarker of neonatal sepsis. Methods: This cross-sectional observational analytic study examines the link between platelet-to-lymphocyte ratio and neonatal sepsis. Based on medical records, this investigation's total number of samples was 36 newborns. Results: From June 2022 to June 2023, there were 539 newborns in the hospital. The prevalence of neonatal sepsis was 23 neonates (4,2%) and there were 14 neonates (2,6%) that fulfilled the criteria in this study. Based on the characteristics of PLR, the mean value in neonatal sepsis was found to be 125.71. Bivariate analysis using statistical Chi-square revealed that PLR had a p-value of 0.009, odds ratio of 6.7, and 95% CI of 1.5 - 29.6. Conclusion: There was a correlation between PLR and neonatal sepsis in Wangaya Hospital. Patients with increased PLR were six times the odds of having neonatal sepsis compared to patients with non-increased PLR.

858. Diagnostic Accuracy of Monocyte Distribution Width as a Sepsis Biomarker in a Large, Urban Emergency Department

Abstract Background Sepsis is a leading cause of hospital and emergency department (ED) mortality, and early identification is crucial. Procalcitonin (PCT), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) are increasingly being utilized to aid in the early identification of septic patients. Recently, monocyte distribution width (MDW), a measure of the range in size of monocytes in the blood, has shown promise as an additional sepsis biomarker; levels > 20 have been correlated with an increased risk of sepsis. This investigation sought to determine the diagnostic accuracy of MDW as a marker of sepsis, and compare the accuracy to that of PCT, CRP, and ESR. Methods This is a retrospective chart review of adult ED patients from 4/1/2022 to 7/31/2022 in whom an MDW was resulted. During this time, MDW was included as part of all CBC reports. We collected PCT, CRP, and ESR results if obtained within 48 hours of the MDW. Sepsis diagnoses were based on a primary ICD-10 diagnosis of sepsis (A40-A41) at ED or hospital discharge. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for MDW in all patients, MDW only in patients with PCT also ordered (regardless of PCT result), PCT, CRP+ESR, and MDW+PCT for the sake of comparison. MDW was considered “positive” for sepsis if > 20. Results There were 10,654 patient encounters with MDW reported. The mean age was 51 years old, and 55% of patients were female. Of the 10,654 encounters, 269 (2.5%) had a sepsis diagnosis on discharge. Diagnostic test results for MDW, PCT, and ESR and CRP are displayed in Table 1. Among all ED patients with a CBC, MDW had a sensitivity, specificity, PPV, and NPV of 82%, 69%, 6.7% and 99%, respectively. In 847 patients where infection was being considered (based on the independent ordering of PCT), MDW sensitivity, specificity, PPV, and NPV were 85%, 53%, 29% and 94%, respectively. MDW was more sensitive but less specific than PCT. In cases of both positive MDW and PCT, the PPV for sepsis was 43%. Conclusion These findings suggest that, as a marker for sepsis, MDW has comparable test characteristics to ESR and CRP, with higher sensitivity but lower specificity than PCT. The combination of a positive MDW and PCT was most predictive of sepsis. Disclosures Ben Hunter, MD, Beckman Coulter: Honoraria

Multilevel omics for the discovery of biomarkers in pediatric sepsis.

Severe sepsis causes organ dysfunction and continues to be the leading reason for pediatric death worldwide. Early recognition of sepsis could substantially promote precision treatment and reduce the risk of pediatric death. The host cellular response to infection during sepsis between adults and pediatrics could be significantly different. A growing body of studies focused on finding markers in pediatric sepsis in recent years using multi-omics approaches. This narrative review summarized the progress in studying pediatric sepsis biomarkers from genome, transcript, protein, and metabolite levels according to the omics technique that has been applied for biomarker screening. It is most likely not a single biomarker could work for precision diagnosis of sepsis, but a panel of markers and probably a combination of markers detected at multi-levels. Importantly, we emphasize the importance of group distinction of infectious agents in sepsis patients for biomarker identification, because the host response to infection of bacteria, virus, or fungus could be substantially different and thus the results of biomarker screening. Further studies on the investigation of sepsis biomarkers that were caused by a specific group of infectious agents should be encouraged in the future, which will better improve the clinical execution of personalized medicine for pediatric sepsis.

The impact of obesity on hospitalized patients with COVID-19 in southern Portugal

COVID-19 is the disease caused by SARS-CoV-2 coronavirus infection, with patients exhibiting asymptomatic or mild clinical manifestations to severe life-threatening respiratory disease. Obesity was early identified as one of the risk factors for the worsening COVID-19 related clinical manifestations. Considering that around a fifth of the Portuguese adult population has obesity, it is pivotal to explore the impact of obesity on COVID-19 clinical outcomes also in this population. To assess the association between obesity and the outcomes of patients hospitalized with COVID-19 in a University Hospital in southern Portugal (Algarve), clinical and biochemical data from a continuous sample of patients was collected and analyzed. Comparisons between patients with and without obesity were performed with appropriate statistical tests. From the 215 patients hospitalized with COVID-19, 24.7% were classified with obesity. Logistic regression showed that patients with obesity were more likely to need intensive care (OR = 2.66; p = 0.009) and higher oxygen requirement (OR = 5.04; p = 0.033), even after adjusting for hypertension (which was more prevalent in the obesity group). Obesity in patients with COVID-19 was not associated with increased mortality, as there were no differences in inflammation or sepsis biomarkers, or the use of corticosteroids/antibiotics, compared to patients without obesity. This work highlights the risk associated with obesity in COVID-19 patients in terms of the course of clinical outcomes. This is the first study analyzing the relationship between obesity and COVID-19 when it comes to clinical outcomes in a Portuguese population from the southern Portugal.

Proteomic Profiling of Early Secreted Proteins in Response to Lipopolysaccharide-Induced Vascular Endothelial Cell EA.hy926 Injury.

Sepsis is a crucial public health problem with a high mortality rate caused by a dysregulated host immune response to infection. Vascular endothelial cell injury is an important hallmark of sepsis, which leads to multiple organ failure and death. Early biomarkers to diagnose sepsis may provide early intervention and reduce risk of death. Damage-associated molecular patterns (DAMPs) are host nuclear or cytoplasmic molecules released from cells following tissue damage. We postulated that DAMPs could potentially be a novel sepsis biomarker. We used an in vitro model to determine suitable protein-DAMPs biomarkers for early sepsis diagnosis. Low and high lipopolysaccharide (LPS) doses were used to stimulate the human umbilical vein endothelial cell line EA.hy926 for 24, 48, and 72 h. Results showed that cell viability was reduced in both dose-dependent and time-dependent manners. Cell injury was corroborated by a significant increase in lactate dehydrogenase (LDH) activity within 24 h in cell-conditioned medium. Secreted protein-DAMPs in the supernatant, collected at different time points within 24 h, were characterized using shotgun proteomics LC-MS/MS analysis. Results showed that there were 2233 proteins. Among these, 181 proteins from the LPS-stimulated EA.hy926 at 1, 12, and 24 h were significantly different from those of the control. Twelve proteins were up-regulated at all three time points. Furthermore, a potential interaction analysis of predominant DAMPs-related proteins using STITCH 5.0 revealed the following associations with pathways: response to stress; bacterium; and LPS (GO:0080134; 0009617; 0032496). Markedly, alpha-2-HS-glycoprotein (AHSG or fetuin-A) and lactotransferrin (LTF) potentially presented since the first hour of LPS stimulation, and were highly up-regulated at 24 h. Taken together, we reported proteomic profiling of vascular endothelial cell-specific DAMPs in response to early an in vitro LPS stimulation, suggesting that these early damage-response protein candidates could be novel early biomarkers associated with sepsis.

Thermal and chronological stability of monocyte distribution width (MDW), the new biomarker for sepsis.

Thermal and chronological stability of monocyte distribution width (MDW), the new biomarker for sepsis.

Cell-free DNA as diagnostic and prognostic biomarkers for adult sepsis: a systematic review and meta-analysis

Although cell-free DNA (cfDNA) is an emerging sepsis biomarker, the use of cfDNA, especially as diagnostic and prognostic indicators, has surprisingly not been systemically analyzed. Data of adult patients with sepsis that conducted cfDNA measurement within 24 h of the admission was collected from PubMed, ScienceDirect, Scopus, and Cochrane Library until October 2022. The Quality in Prognosis Studies (QUIPS) and Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools were used to reduce the risk of biased assessment. The mean difference (MD) of cfDNA concentration and the standardized mean difference (SMD) between populations was calculated using Review Manager (RevMan) version 5.4.1 package software. Pooled analysis from 18 included studies demonstrated increased serum cfDNA levels in sepsis when compared with healthy control (SMD = 1.02; 95% confidence interval (CI) 0.46–1.57) or non-sepsis patients in the intensive care unit (ICU) (SMD = 1.03; 95% CI 0.65–1.40), respectively. Meanwhile, a slight decrease in the statistical value was observed when compared with non-sepsis ICU patients with SIRS (SMD = 0.74; 95% 0.41–1.06). The lower cfDNA levels were also observed in sepsis survivors compared to the non-survivors (SMD at 1.43; 95%CI 0.69–2.17) with the pooled area under the receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.64–0.87) for the mortality prediction. Levels of cfDNA showed a pooled sensitivity of 0.81 (95% CI 0.75–0.86) and specificity of 0.72 (95% CI 0.65–0.78) with pooled diagnostic odd ratio (DOR) at 25.03 (95% CI 5.48–114.43) for the identification of sepsis in critically ill conditions. The cfDNA levels were significantly higher in patients with sepsis and being a helpful indicator for the critically ill conditions of sepsis. Nevertheless, results of the test must be interpreted carefully with the context of all clinical situations.

Three-dimensional label-free morphology of CD8 + T cells as a sepsis biomarker

Sepsis is a dysregulated immune response to infection that leads to organ dysfunction and is associated with a high incidence and mortality rate. The lack of reliable biomarkers for diagnosing and prognosis of sepsis is a major challenge in its management. We aimed to investigate the potential of three-dimensional label-free CD8 + T cell morphology as a biomarker for sepsis. This study included three-time points in the sepsis recovery cohort (N = 8) and healthy controls (N = 20). Morphological features and spatial distribution within cells were compared among the patients’ statuses. We developed a deep learning model to predict the diagnosis and prognosis of sepsis using the internal cell morphology. Correlation between the morphological features and clinical indices were analysed. Cell morphological features and spatial distribution differed significantly between patients with sepsis and healthy controls and between the survival and non-survival groups. The model for predicting the diagnosis and prognosis of sepsis showed an area under the receiver operating characteristic curve of nearly 100% with only a few cells, and a strong correlation between the morphological features and clinical indices was observed. Our study highlights the potential of three-dimensional label-free CD8 + T cell morphology as a promising biomarker for sepsis. This approach is rapid, requires a minimum amount of blood samples, and has the potential to provide valuable information for the early diagnosis and prognosis of sepsis.

Diagnostic Accuracy of Serum Presepsin as Biomarker of Bacterial Sepsis in Paediatric Patients

Diagnostic Accuracy of Serum Presepsin as Biomarker of Bacterial Sepsis in Paediatric Patients

Lysosome-Related Diagnostic Biomarkers for Pediatric Sepsis Integrated by Machine Learning.

There is currently no biomarker that can reliably identify sepsis, despite recent scientific advancements. We systematically evaluated the value of lysosomal genes for the diagnosis of pediatric sepsis. Three datasets (GSE13904, GSE26378, and GSE26440) were obtained from the gene expression omnibus (GEO) database. LASSO regression analysis and random forest analysis were employed for screening pivotal genes to construct a diagnostic model between the differentially expressed genes (DEGs) and lysosomal genes. The efficacy of the diagnostic model for pediatric sepsis identification in the three datasets was validated through receiver operating characteristic curve (ROC) analysis. Furthermore, a total of 30 normal samples and 35 pediatric sepsis samples were gathered to detect the expression levels of crucial genes and assess the diagnostic model's efficacy in diagnosing pediatric sepsis in real clinical samples through real-time quantitative PCR (qRT-PCR). Among the 83 differentially expressed genes (DEGs) related to lysosomes, four key genes (STOM, VNN1, SORT1, and RETN) were identified to develop a diagnostic model for pediatric sepsis. The expression levels of these four key genes were consistently higher in the sepsis group compared to the normal group across all three cohorts. The diagnostic model exhibited excellent diagnostic performance, as evidenced by area under the curve (AUC) values of 1, 0.971, and 0.989. Notably, the diagnostic model also demonstrated strong diagnostic ability with an AUC of 0.917 when applied to the 65 clinical samples, surpassing the efficacy of conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%). A four-gene diagnostic model of lysosomal function was devised and validated, aiming to accurately detect pediatric sepsis cases and propose potential target genes for lysosomal intervention in affected children.

High Plasma Presepsin Levels in Children With Hemophagocytic Lymphohistiocytosis.

Presepsin is reported as a novel diagnostic and prognostic biomarker for sepsis, and its optimal cutoff value is reported to be 600 to 650pg/mL. Three children were diagnosed with hemophagocytic lymphohistiocytosis (HLH). The cause of HLH was unknown in cases 1 and 2, while Epstein-Barr virus infection was the cause in case 3. The plasma presepsin levels at the diagnosis were 1020, 1080, and 3160pg/mL in cases 1, 2, and 3, respectively. In case 1, the plasma level of presepsin decreased to 164pg/mL on day 19 of her sickness, when symptoms improved. Follow-up plasma presepsin levels were missing for cases 2 and 3. No microbiological pathogens were detected in the blood cultures of any of the patients. Our cases suggest that plasma presepsin levels can be elevated in childhood HLH.