Diagnostic Biomarker Of Sepsis Research Articles

ANXA3 as a novel biomarker for sepsis diagnosis: Evidence from integrative WGCNA analysis

Sepsis is a dysregulated immune response to infection that comes with multiple organ dysfunction and high mortality. The management of sepsis relies heavily on early recognition and diagnosis, but current diagnostic methods have limitations in timeliness, sensitivity, and discriminability. This study aims to discover novel biomarkers for sepsis diagnosis. Four datasets from different regions were analyzed using weighted gene co-expression network analysis (WGCNA), and genes with high Gene Significance values across these datasets were overlapped. Finally, two genes, CD177 and ANXA3, were identified. ANXA3 was validated as a potential sepsis biomarker by checking multiple datasets and Receiver Operating Characteristic (ROC) Curve Analysis. Of note, ANXA3 could distinguish not only between adult and child sepsis patients and healthy controls, but also between septic shock and cardiogenic shock. Moreover, a murine sepsis model was established and the results showed that the transcription of ANXA3 in peripheral blood of septic mice was significantly higher than that of healthy controls, while Escherichia coli infection alone did not significantly increase the transcription level of this gene. Subsequent studies of sepsis in mice revealed that the predictive effect of Anxa3 on sepsis could be observed as early as 6 h post-modeling. Interestingly, ANXA3 expression was predominantly up-regulated in myeloid cells, up-regulated in spleen, down-regulated in lung, and not detected in liver after sepsis modeling. Taken together, this study provides a way for the discovery of biomarkers and finds that ANXA3 may be a novel diagnostic biomarker for sepsis.

Differential expression of plasma cytokines in sepsis patients and their clinical implications.

Sepsis, which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality, presents a significant challenge in health care. Some scholars have found that the sequential organ failure assessment (SOFA) and quick SOFA scores are not ideal for predicting severe sepsis and mortality. Microbial culture takes a long time (2-3 d) and provides no information for early diagnosis and treatment. Therefore, new diagnostic methods for sepsis need to be explored. To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis. Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group, whereas ten noninfected patients served as the control group. Of the 10 noninfected patients, 9 hypertension combined with cerebral infarction, 1 patients with vertiginous syndrome. Plasma Cytokines were measured using the Bio-Plex Pro™ Human Chemokine Panel 40-plex. Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Interleukin (IL)-16, granulocyte-macrophage granulocyte-macrophage colony-stimulating factor (GM-CSF), CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 plasma levels were significantly increased in sepsis patients. GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates, nuclear plaques, adhesion plaques, lateral plasma membranes, and cell matrix junctions. These genes were involved in various molecular functions, such as cytokine activity, receptor ligand activity, and signal receptor activator activity, contributing to various biological functions, such as leukocyte chemotaxis, migration, and chemotaxis. KEGG analysis indicated involvement in cytokine cytokine receptor interactions, chemokine signaling pathways, virus-protein interactions with cytokines and cytokine receptors, and the tumor necrosis factor signaling pathway. Elevated serum levels of IL-16, GM-CSF, CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

Comprehensive analysis of sialylation-related genes and construct the prognostic model in sepsis

Sepsis, a life-threatening syndrome, continues to be a significant public health issue worldwide. Sialylation is a hot potential marker that affects the surface of a variety of cells. However, the role of genes related to sialylation and sepsis has not been fully explored. Bulk RNA-seq data sets (GSE66099 and GSE65682) were obtained from the open-access databases GEO. The classification of sepsis samples into subtypes was achieved by employing the R package “ConsensusClusterPlus” on the bulk RNA-seq data. Hub genes were discerned through the application of the R package “limma” and univariate regression analysis, with the calculation of risk scores carried out using the R package “survminer”. To identify the best learning method and construct a prognostic model, we used 21 different combinations of machine learning, and C-index ranking results of these combinations have been showed. ROC curves, time-dependent ROC curves, and Kaplan–Meier curves were utilized to evaluate the diagnostic accuracy of the model. The R packages “ESTIMATE” and “GSVA” were employed to quantify the fractions of immune cell infiltration in each sample. The bulk RNA-seq samples were categorized into two distinct sepsis subtypes utilizing 14 prognosis-related sialylation genes. A total of 20 differentially expressed genes (DEGs) were identified as being associated with the relationship between sepsis and sialylation. The RSF was used to identify key genes with importance scores higher than 0.01. The nine hub genes (SLA2A1, TMCC2, TFRC, RHAG, FKBP1B, KLF1, PILRA, ARL4A, and GYPA) with the importance values greater than 0.01 was selected for constructing the prognostic model. This research offers some understanding of the relationship between sepsis and sialylation. Besides, it contains one predictive model that might develop into diagnostic biomarkers for sepsis.

Diagnostic and Predictive Value of LncRNA MCM3AP-AS1 in Sepsis and Its Regulatory Role in Sepsis-Induced Myocardial Dysfunction.

The present study focused on exploring the clinical value and molecular mechanism of LncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in sepsis and sepsis-induced myocardial dysfunction (SIMD). 122 sepsis patients and 90 healthy were included. Sepsis patients were categorized into SIMD and non-MD. The expression levels of MCM3AP-AS1 and miRNA were examined using RT-qPCR. Diagnostic value of MCM3AP-AS1 in sepsis assessed by ROC curves. Logistic regression to explore risk factors influencing the occurrence of SIMD. Cardiomyocytes were induced by LPS to construct cell models in vitro. CCK-8, flow cytometry, and ELISA to analyze cell viability, apoptosis, and inflammation levels. Serum MCM3AP-AS1 was upregulated in patients with sepsis. The sensitivity and specificity of MCM3AP-AS1 were 75.41% and 93.33%, for recognizing sepsis from healthy controls. Additionally, elevated MCM3AP-AS1 is a risk factor for SIMD and can predict SIMD development. Compared with the LPS-induced cardiomyocytes, inhibition of MCM3AP-AS1 significantly attenuated LPS-induced apoptosis and inflammation; however, this attenuation was partially reversed by lowered miR-28-5p, but this reversal was partially eliminated by CASP2. MCM3AP-AS1 may be a novel diagnostic biomarker for sepsis and can predict the development of SIMD. MCM3AP-AS1 probably participated in SIMD progression by regulating cardiomyocyte inflammation and apoptosis through the target miR-28-5p/CASP2 axis.

Serum Ferritin and Procalcitonin as Diagnostic Biomarkers for Sepsis in an Emergency Department: A Clinical Study

Abstract Background and Aim: Sepsis, a life-threatening condition, presents diagnostic challenges due to its heterogeneous nature. Early and accurate diagnosis is essential for timely intervention. Serum biomarkers, such as ferritin and procalcitonin (PCT), have been explored for their potential in sepsis diagnosis, but the outcomes are inconclusive. The current study was an attempt to further explore the usefulness of ferritin and PCT as sepsis biomarkers. Material and Methods: A prospective study involving 149 patients assessed serum ferritin and PCT levels in those with features suggestive of sepsis. Patients were categorized into sepsis and nonsepsis groups based on the clinical judgment of the emergency physicians. Statistical analyses, including the Mann–Whitney U test and receiver operating characteristic (ROC) curves, were conducted to evaluate the diagnostic utility of these biomarkers. Results: Serum ferritin levels did not exhibit a statistically significant difference between sepsis and nonsepsis groups (P = 0.698). In contrast, PCT levels were significantly higher in sepsis cases (P = 0.011). ROC analysis identified an optimal PCT cutoff value of 0.085, offering high sensitivity (92.5) but lower specificity (16.7). Conclusion: PCT proved valuable as a diagnostic marker for sepsis. Serum ferritin, on the other hand, did not demonstrate statistical significance as a diagnostic marker for sepsis, its potential role in specific septic conditions and disease severity monitoring warrants further investigation.

Unlocking the potential of senescence-related gene signature as a diagnostic and prognostic biomarker in sepsis: insights from meta-analyses, single-cell RNA sequencing, and in vitro experiments.

Cellular senescence is closely associated with the pathogenesis of sepsis. However, the diagnostic and prognostic value of senescence-related genes remain unclear. In this study, 866 senescence-related genes were collected from CellAge. The training cohort, GSE65682, which included 42 control and 760 sepsis samples, was obtained from the Gene Expression Omnibus (GEO). Feature selection was performed using gene expression difference detection, LASSO analysis, random forest, and Cox regression. TGFBI and MAD1L1 were ultimately selected for inclusion in the multivariate Cox regression model. Clustering based on the expressions of TGFBI and MAD1L1 was significantly associated with sepsis characteristics and prognoses (all P < 0.05). The risk signature served as a reliable prognostic predictor across the GSE65682, GSE95233, and GSE4607 cohorts (pooled hazard ratio = 4.27; 95% confidence interval [CI] = 1.63-11.17). Furthermore, it also served as a robust classifier to distinguish sepsis samples from control cases across 14 cohorts (pooled odds ratio = 5.88; 95% CI = 3.54-9.77). Single-cell RNA sequencing analyses from five healthy controls and four sepsis subjects indicated that the risk signature could reflect the senescence statuses of monocytes and B cells; this finding was then experimentally validated in THP-1 and IM-9 cells in vitro (both P < 0.05). In all, a senescence-related gene signature was developed as a prognostic and diagnostic biomarker for sepsis, providing cut-in points to uncover underlying mechanisms and a promising clinical tool to support precision medicine.

A-256 Clinical Performance of Presepsin for Sepsis in the Emergency Department Patients in a Tertiary Hospital in Korea

Abstract Background Sepsis is a life-threatening condition that requires prompt recognition and treatment. Presepsin is a new diagnostic biomarker of sepsis that has been implemented as a selective reimbursement in Korea and was introduced in our hospital in October 2022. This study aimed to evaluate the clinical performance of the Presepsin Assay (Sysmex, Kobe, Japan) on the Sysmex HISCL-5000 system in the southeast population in Korea. Methods The study is a retrospective study that included emergency department (ED) and ED-based intensive care unit (EICU) patients tested for presepsin from August 18, 2022, to February 11, 2023. We calculated the patients’ sepsis-related organ failure assessment (SOFA) score at the time of blood collection for presepsin from the electronic medical record. Presepsin, procalcitonin, and high-sensitivity C-reactive protein (hsCRP) were also investigated. The sepsis markers for sepsis prediction were evaluated using receiver operating characteristic (ROC) curve analysis and area under the curve (AUC). Results A total of 81 patients, including 66 ED and 15 EICU patients, were tested for presepsin. The presepsin results ranged from 101 to 8788 pg/mL (Mean 1,005.9 pg/mL, Standard deviation 1,509.4). In ROC curve analysis, three biomarkers—presepsin, procalcitonin, and hsCRP generated an area under the curve (AUC) value of 0.698, 0.670, and 0.694 for predicting sepsis, respectively, for the threshold ≥7 of SOFA score to screen the risk of sepsis. Conclusion The clinical performance of presepsin in the ED-based setting in Korea was found to be comparable in detecting the risk of sepsis. Further research is needed to determine the optimal use of presepsin in the other clinical areas of the hospital, such as intensive care units, and to assess its impact on patient outcomes.

Evidence for the circulating microRNA hsa-let-7d-3p as a potential new biomarker for sepsis in human subjects

BackgroundCurrent biomarkers for the early detection of sepsis have low sensitivity and specificity. Serum microRNAs (miRNAs) have been proposed as novel noninvasive biomarkers for various diseases. The aim of the present study was to discover a novel diagnostic biomarker for sepsis in human subjects.MethodsmiRNA expression profiling was performed using peripheral blood from three sepsis patients in the sepsis stage and improved condition stage using microarray screening. The differentially expressed miRNAs were primary validated by real-time quantitative polymerase chain reaction (RT-qPCR) in a further set of 20 sepsis patients in the sepsis stage and improved condition stage. Finally, we validated the differentially expressed miRNAs in 95 sepsis patients and 66 nonsepsis patients. The validated miRNAs and patients’ clinical indictors were analysed in a multivariate logistic regression model. The diagnostic value of the changed miRNA in sepsis was determined and compared with CRP and WBC by analysing the receiver operating characteristic (ROC) curves.ResultsAccording to the criteria, we detected 11 miRNAs regulated by the miRNA chip. RT-qPCR detection showed that the expression of hsa-let-7d-3p in sepsis patients was upregulated compared with that in nonsepsis patients. In a multiple logistic regression analysis, serum miRNA hsa-let-7d-3p was found to be an independent predictor of sepsis. Receiver operating characteristic curve (ROC) analysis showed that the area under the ROC curve of serum hsa-let-7d-3p was 0.696 [95% confidence interval (0.615, 0.778)].ConclusionThe miRNA hsa-let-7d-3p was identified as a novel biomarker for the early detection of sepsis.

Circular RNAs in the pathogenesis of sepsis and their clinical implications: A narrative review

Sepsis is defined as a life-threatening complication that occurs when the body responds to an infection attacking the host. Sepsis rapidly progresses and patients deteriorate and develop septic shock, with multiple organ failure, if not promptly treated. Currently no effective therapy is available for sepsis; therefore, early diagnosis is crucial to decrease the high mortality rate. Genome-wide expression analyses of patients in critical conditions have confirmed that the expression levels of the majority of genes are changed, suggesting that the molecular basis of sepsis is at the gene level. This review aims to elucidate the role of circular (circ) RNAs in the pathogenesis of sepsis and sepsis-induced organ damage. In addition, the feasibility of using circRNAs as novel diagnostic biomarkers for sepsis is also discussed, as well as circRNA-based therapy. This narrative review is based on a literature search using Medline database. Search terms used were "circular RNAs and sepsis", "circRNAs and sepsis", "non-coding RNAs and sepsis", "ncRNAs and sepsis", "circRNAs and septic pathogenesis", "circRNAs and septic model", "circRNAs and septic shock" and "circRNAs, biomarker, and sepsis". Numerous studies indicate that circRNAs might exert pivotal roles in regulating the immune system of the host against various pathogens, such as bacteria and viruses. Dysregulation of circRNA expression levels has been confirmed as an early event in sepsis and associated with the inflammatory response, immunosuppression and coagulation dysfunction. This impairment in regulation eventually leads to multiple organ dysfunctions, including of the kidneys, lungs and heart. By investigating the regulation of circRNAs in sepsis, new molecular targets for the diagnosis and intervention of sepsis can be identified. Such an understanding will be important for the development of therapeutic drugs.

Serum Mannose Receptor as a Diagnostic Bio-Marker for Sepsis in ICU Patients in Ain Shams University Hospitals

Serum Mannose Receptor as a Diagnostic Bio-Marker for Sepsis in ICU Patients in Ain Shams University Hospitals

Ultrasensitive and label-free detection of prognostic and diagnostic biomarkers of sepsis on a AgNP-laden black phosphorous-based SERS platform

Rapid and early detection of sepsis biomarkers using AgNP@BP SERS substrate and identification of signature Raman modes of sepsis biomarkers (IL-3 and PCT).

MiR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes.

BackgroundAs a molecular detection method, miRNA can quickly diagnose and prevent diseases, intervene in disease as early as possible, and reduce mortality. This study was to investigate the potential clinical diagnostic and predictive significance of miR-486-5p in sepsis and its correlation with inflammation and disease severity.MethodsThe serum miR-486-5p in 108 sepsis, 60 pneumonia-infected, and 101 healthy controls were detected by RT-qPCR. Spearman coefficient detects the correlation between serum miRNA and disease severity indicators (APACHE II, SOFA scores), and inflammation indicators (CRP, PCT), respectively. The diagnostic significance of miR-486-5p in sepsis was analyzed by the ROC curve. Kaplan–Meier estimator and Cox regression hazards analysis of the predictive significance of serum miR-486-5p in 28-day survival from sepsis.ResultsSerum miR-486-5p was increased in sepsis patients compared with healthy control and pneumonia-infected patients (P < 0.001). And increased serum miR-486-5p was positively associated with disease severity (SOFA score and APACHE II score) and inflammation (CRP and PCT). Serum miR-486-5p can not only identify sepsis patients from healthy controls (AUC = 0.914) but also significantly distinguish sepsis patients from pneumonia-infected patients (AUC = 0.814), showing good potential as a diagnostic biomarker for sepsis. In addition, serum miR-486-5p was an independent predictor of 28-day survival (log-rank P = 0.012), and patients with high levels of miR-486-5p had a poorer overall 28-day survival (HR = 3.057, 95% CI = 1.385–17.817, P = 0.014).ConclusionmiR-486-5p is a potential diagnostic biomarker for sepsis, and its high level is significantly correlated with the disease severity and inflammation. In addition, miR-486-5p were predictive risk factors for 28-day survival in sepsis patients.

Soluble urokinase-type plasminogen activator receptor as a diagnostic biomarker for sepsis in intensive care unit patients

Background: Sepsis is one of the main causes of morbidity and mortality in the intensive care units (ICUs).It is difficult to differentiate it accurately and timely from other confusing conditions. So, it is of utmost importance to evaluate new biomarkers with a differentiation ability between sepsis and non-sepsis conditions. Soluble urokinase-type plasminogen activator receptor (suPAR) is a stable biomarker of inflammation. The aim of the study is to evaluate the value of suPAR in the diagnosis of septic ICU patients and to compare it (if present) with that of C-reactive protein (CRP) and procalcitonin (PCT).Methods: A case-control study was conducted at Zagazig University Hospitals from December 2017 to October 2019. A total of 90 subjects were enrolled in the study. Based on Systemic Inflammatory Response Syndrome (SIRS) criteria, they were divided into 2 groups: (i)Group A: 60 septic ICU admitted patients;(ii)Group B: 30 non-septic ICU admitted patients as control group.Single determination of level of serum suPAR was measured by enzyme-linked immunosorbent assay (ELISA) for all the participants.Results: Septic ICU patients had statistically significant higher serum suPAR, CRP and PCT levels than non-septic patients. suPAR had a sensitivity of 72%, specificity of 70% and AUC of 0.7 in sepsis diagnosis.Conclusion: Serum suPAR is a fair diagnostic test for septic ICU patients at cut-off 3.983 ng/ml but does not surpass that of PCT or CRP.

Procalcitonin kinetics early after severe burn injury and its value in diagnosis of sepsis

PurposeTo investigate the clinical significance of procalcitonin (PCT) kinetics early after burn and the perioperative period, and to assess its diagnostic performance for sepsis in major burn patients. MethodsThis retrospective study on major burn patents (≥40% total body surface area) admitted from 2014 to 2019 was conducted in Southwest Hospital, Chongqing, China. A total of 321 patients were included. The kinetics of PCT was analyzed during the 1st week after burn, the perioperative period, and at the onset of clinical suspected sepsis. ResultsSerum PCT concentration rose immediately after burn injury. Factors associated with increased PCT level in the 1st week after burn include greater burn area (>70% TBSA) and lower age (≤14 years). Correlations between PCT kinetics after burn and the risk of early development of sepsis and mortality were observed. At the onset of sepsis, serum PCT increased significantly compared to its basal level in the 48 h before diagnosis. The area under the receiver operating characteristics curve of PCT concentration and its kinetic changes was 0.788 and 0.826, respectively. PCT kinetics showed better accuracy than PCT concentration in discrimination of Gram-positive sepsis. The optimal diagnostic thresholds for PCT concentration and its kinetics were 1.41 ng/mL, and a 1.34-fold elevation compared to the baseline level. ConclusionsPCT kinetics in the early stage after burn was a prognostic factor for sepsis and mortality among major burn patients. Serum PCT levels could be a diagnostic biomarker for sepsis in major burn patients.

Presepsin, Procalcitonin and C Reactive Protein as Diagnostic Biomarkers of Sepsis in Intensive Care Unit Patients

Background: Sepsis is a global, life-threatening health priority. Blood culture is the gold standard of diagnosis sepsis; however, it requires several days, which delays the diagnosis of the sepsis. Biomarkers could play a pivotal role in diagnosis, grading and predicting the outcome of sepsis. Objectives: were to assess the potential role of CRP, PCT and presepsin for diagnosis, grading and predict the prognosis of sepsis.Patients and methods: The study included 58 patients, 28 patients diagnosed with sepsis, and 28 ICU patients presented by different presentation but with no sepsis. For patients with sepsis, APACHE II score was calculated, Blood culture was done using BacT/Alert system, and Vitek 2 to identify bacterial isolates. For all subjects included in the study, quantitative measurement of CRP, PTC and presepsin were done using PA54 Specific Protein Analyzer, VIDAS® immune-analyzer, and PATHFAST fully automated immunoassay analyzer respectively.Results: APACHE II score positively correlated with PCT (p=0.026) and presepsin (p=0.034), but not CRP (p=0.291). Differences between cases and control group for the three biomarkers’ levels) were statistically significant (P value

Clinical value of microRNA-378a-3p in sepsis and its role in sepsis-induced inflammation and cardiac dysfunction

ABSTRACT This study explored the clinical meaning of miR-378a-3p in sepsis and its influence on sepsis-induced inflammation and cardiac dysfunction. Serum levels of miR-378a-3p were detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Receiver Operating Characteristic (ROC) curve was used to evaluate its diagnostic value. The effects of miR-378a-3p on inflammation and cardiac function were evaluated by monitoring left ventricular systolic pressure (LVSP), left ventricular and end-diastolic pressure (LVEDP), maximum rate of change in left ventricular pressure (± dp/dtmax) and detecting the levels of troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interleukin-1β (IL-1β) via enzyme linked immunosorbent assay (ELISA). Serum miR-378a-3p was increased in sepsis patients and rat model. ROC curve indicated that miR-378a-3p might have diagnostic significance for sepsis miR-378a-3p antagomir improved the cardiac function by upregulating the levels of LVSP and ± dp/dtmax, and decreasing the levels of LVEDP, cTnI and CK-MB in rat model. miR-378a-3p antagomir also significantly alleviated the inflammatory responseby down-regulating the expression of TNF-a, IL-6, and IL-1β. Besides, logistics regression analysis illustrated that miR-378a-3p was an independent influencing factor for the onset of cardiac dysfunction in sepsis. miR-378a-3p has the potential as a diagnostic biomarker for sepsis and decreasing the level of miR-378a-3p had the ability to ameliorate cardiac dysfunction and inflammatory response caused by sepsis.

Circular RNAs in Sepsis: Biogenesis, Function, and Clinical Significance.

Sepsis is a life-threatening condition that occurs when the body responds to an infection that damages it is own tissues. The major problem in sepsis is rapid, vital status deterioration in patients, which can progress to septic shock with multiple organ failure if not properly treated. As there are no specific treatments, early diagnosis is mandatory to reduce high mortality. Despite more than 170 different biomarkers being postulated, early sepsis diagnosis and prognosis remain a challenge for clinicians. Recent findings propose that circular RNAs (circRNAs) may play a prominent role in regulating the patients’ immune system against different pathogens, including bacteria and viruses. Mounting evidence also suggests that the misregulation of circRNAs is an early event in a wide range of diseases, including sepsis. Despite circRNA levels being altered in sepsis, the specific mechanisms controlling the dysregulation of these noncoding RNAs are not completely elucidated, although many factors are known to affect circRNA biogenesis. Therefore, there is a need to explore the molecular pathways that lead to this disorder. This review describes the role of this new class of regulatory RNAs in sepsis and the feasibility of using circRNAs as diagnostic biomarkers for sepsis, opening up new avenues for circRNA-based medicine.

Procalcitonin and Bacterial Sepsis in Burn Patients in South Africa

BackgroundBurn patients are at high risk of infection, and as sepsis contributes significantly to morbidity and mortality, early diagnosis is essential. Procalcitonin (PCT) is a biomarker released in response to inflammation and specifically bacterial infection. This study aimed to determine the value of PCT as a diagnostic biomarker of sepsis in burns patients in Johannesburg, South Africa. Materials and methodsAll adult patients admitted to two burns intensive care units in Johannesburg over a 3-year study period were included in a retrospective data review. Records of 178 patients were accessible and reviewed. ResultsThe most significant risk factor for sepsis was percentage total body surface area burned (P = 0.012). A rise in PCT was a significant biomarker for bacterial infection in the early phase after a burn (P = 0.03) but not after day eight. PCT correlated with C-reactive protein as a biomarker for sepsis (P < 0.001), but not with other biomarkers. The mean PCT in patients who died was significantly higher on every study day until death compared with those who remained alive (P < 0.02, consistently). Patients on inotropes also had a significantly increased PCT level (P = 0.0001), as did those who were not discharged from intensive care unit by day 14. ConclusionsPCT may be useful as an adjunct biomarker of infection in burn patients and has potential as a predictive biomarker of early discharge.

Serum developmental endothelial locus-1 is associated with severity of sepsis in animals and humans

Disruption of the endothelial glycocalyx has a prominent role in the pathophysiology of sepsis. Developmental endothelial locus-1 (Del-1) is an endothelial-derived anti-inflammatory factor. We hypothesized that degradation of the endothelial glycocalyx during sepsis may increase serum Del-1. A mouse model of sepsis was created using cecal ligation and puncture. In septic mice, the endothelial glycocalyx was nearly completely degraded, with less formation of Del-1 in the endothelium and extracellular matrix than in control mice. Serum Del-1 levels were significantly increased in the septic mice with increasing severity of sepsis. Serum Del-1 levels were also measured in 84 patients with sepsis and septic shock and in 20 control subjects. The median serum Del-1 level in patients with sepsis was significantly higher than that in healthy controls. The high Del-1 group had higher illness severity scores and contained more patients with organ dysfunction than the low Del-1 group. The 90-day mortality rate was significantly higher in the high Del-1 group than in the low Del-1 group. Multivariate analysis indicated a tendency for a high serum Del-1 level to be associated with a higher mortality risk. Increased serum Del-1 may be a novel diagnostic biomarker of sepsis and an indicator of disease severity.

Procalcitonin as a diagnostic biomarker of sepsis: A tertiary care centre experience

IntroductionDespite the advancement in diagnostic modalities of sepsis, it is still a leading cause of morbidity and mortality. Differentiation between sepsis and non-infectious disease states remains a diagnostic challenge. Procalcitonin (PCT) is useful for the diagnosis of sepsis but it varies in cut-off ranges at different clinical settings. The aim of this study was to correlate serum PCT levels with cultures and to evaluate the best cut-off values with high sensitivity and specificity for PCT. MethodologyThis prospective study included 305 patients from different medical wards; the patients were classified into group I: controls (n=46), group II: culture-negative sepsis (n=76) and group III: culture-positive sepsis (n=196). Mean p value <0.05 was considered significant. ResultsPCT levels were significantly higher in group II and group III as compared with group I. In group II, the best cut-off point for PCT was 1.3ng/ml with 87.30% sensitivity and 78.26% specificity (area under curve 0.86). In group III, the best cut-off value of 2.20ng/ml with 98.47% sensitivity and 89.13% specificity was found (AUC 0.96). ConclusionProcalcitonin can accurately differentiate culture-negative and culture-positive sepsis from non-infectious diseases, thus making it a promising biomarker in diagnosis of bacterial sepsis.