Accurate Diagnosis Of Sepsis Research Articles

Heparin-binding protein as a biomarker for the diagnosis of sepsis in the intensive care unit: a retrospective cross-sectional study in China

ObjectivesThis study aims to investigate the diagnostic value of heparin-binding protein (HBP) in sepsis and develop a sepsis diagnostic model incorporating HBP with key biomarkers and disease-related scores for rapid,...

Effect of HMGB1 and HBD-3 levels in the diagnosis of sepsis- A comparative descriptive study

Sepsis is a life-threatening condition characterized by a dysregulated host response to infection. Early and accurate diagnosis of sepsis is crucial for timely intervention and improved patient outcomes. In recent years, there has been growing interest in identifying reliable biomarkers to aid in the diagnosis of sepsis. This study aims to evaluate the levels of two potential biomarkers, high-mobility group box 1 (HMGB1) and human β-defensin 3 (HBD-3), and compare their diagnostic efficacy in sepsis.We aimed to assess HMGB-1 and HBD-3 levels in sepsis and assess the combined diagnostic validity of HMGB-1 and HBD-3. In this case-control study, the plasma concentration of HMGB-1 and HBD-3 was measured using an enzyme-linked immunosorbent assay (ELISA). Two groups, totaling 144 people, were formed; 66 patients treated in the ICU for sepsis were included in the patient group. 78 Blood donors from the Salmaniya Medical Complex Blood Bank who had no prior infection or inflammatory disease made up the Control group. The statistical computations were performed using the STATA 8® statistical software tool (StataCorp LP, College Station, TX, USA).In patients' mean HMGB-1 levels were 2.1442 ng/ml, compared to 0.62141 ng/ml in the control group. The mean HBD-3 level was 1068.453 ng/ml in sepsis patients versus 589.935 ng/ml in controls. A significant difference between the two groups has been observed in both biomarkers (P < 0.05). The sensitivity of HMGB-1 was 75.8% and 41.3%, respectively. The sensitivity and specificity of HBD-3 were 63.6% and 93.5%, respectively.The levels of HMGB-1 and HBD-3 between healthy and septic subjects varied significantly. HMGB-1 and HBD-3 levels in the blood tested together might accurately identify sepsis. These findings contribute to the growing body of evidence supporting the utility of biomarkers in sepsis diagnosis, and may ultimately aid in the development of more effective diagnostic strategies for sepsis management.

Comprehensive Comparison of the Capacity of Functionalized Sepharose, Magnetic Core, and Polystyrene Nanoparticles to Immuno-Precipitate Procalcitonin from Human Material for the Subsequent Quantification by LC-MS/MS

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The fast and accurate diagnosis of sepsis by procalcitonin (PCT) has emerged as an essential tool in clinical medicine. Although in use in the clinical laboratory for a long time, PCT quantification has not yet been standardized. The International Federation of Clinical Chemistry working group on the standardization of PCT (IFCC-WG PCT) aims to provide an LC-MS/MS-based reference method as well as the highest metrological order reference material to address this diagnostic need. Here, we present the systematic evaluation of the efficiency of an immuno-enrichment method, based on functionalized Sepharose, magnetic-core, or polystyrene (latex) nano-particles, to quantitatively precipitate PCT from different human sample materials. This method may be utilized for both mass spectrometric and proteomic purposes. In summary, only magnetic-core nano-particles functionalized by polyclonal PCT antibodies can fulfil the necessary requirements of the international standardization of PCT. An optimized method proved significant benefits in quantitative and specific precipitation as well as in the subsequent LC-MS/MS detection of PCT in human serum samples or HeLa cell extract. Based on this finding, further attempts of the PCT standardization process will utilize a magnetic core-derived immuno-enrichment step, combined with subsequent quantitative LC-MS/MS detection.

Labeled TEMPO-Oxidized Mannan Differentiates Binding Profiles within the Collectin Families.

Establishing the rapid and accurate diagnosis of sepsis is a key component to the improvement of clinical outcomes. The ability of analytical platforms to rapidly detect pathogen-associated molecular patterns (PAMP) in blood could provide a powerful host-independent biomarker of sepsis. A novel concept was investigated based on the idea that a pre-bound and fluorescent ligand could be released from lectins in contact with high-affinity ligands (such as PAMPs). To create fluorescent ligands with precise avidity, the kinetically followed TEMPO oxidation of yeast mannan and carbodiimide coupling were used. The chemical modifications led to decreases in avidity between mannan and human collectins, such as the mannan-binding lectin (MBL) and human surfactant protein D (SP-D), but not in porcine SP-D. Despite this effect, these fluorescent derivatives were captured by human lectins using highly concentrated solutions. The resulting fluorescent beads were exposed to different solutions, and the results showed that displacements occur in contact with higher affinity ligands, proving that two-stage competition processes can occur in collectin carbohydrate recognition mechanisms. Moreover, the fluorescence loss depends on the discrepancy between the respective avidities of the recognized ligand and the fluorescent mannan. Chemically modulated fluorescent ligands associated with a diversity of collectins may lead to the creation of diagnostic tools suitable for multiplex array assays and the identification of high-avidity ligands.

Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis

Sepsis is a severe life-threatening and rapidly developing disease that causes millions of deaths annually worldwide. Researchers have made tremendous efforts to elucidate the pathophysiology of sepsis using various animal models; the mouse model of sepsis induced by cecal ligation and puncture (CLP) is widely used in laboratories. The three technical aspects that affect the severity and replicability of the CLP model are the percentage of cecum ligated, the size of the needle used for cecal puncture, and the volume of feces squeezed into the abdominal cavity. The rapid and specific diagnosis of sepsis is a crucial factor that affects the outcome. The gold standard for sepsis diagnosis is microbial culture; however, this process is time-consuming and sometimes inaccurate. The detection of sepsis-specific biomarkers is fast, but the existing biomarkers are unsatisfactory due to a short half-life, non-specificity, and insufficient sensitivity. Therefore, there is an urgent need for a reliable biomarker of sepsis in the early stages. Previous publications suggest that excessive neutrophil extracellular traps (NETs) occur in sepsis. Citrullinated histone H3 (CitH3), as a NET component, is elevated both in septic animals and patients, and the presence of CitH3 is a reliable diagnostic biomarker of sepsis. The present study aimed to describe a standardized mouse model of CLP-induced sepsis and establish a reliable blood biomarker of sepsis. Our work may contribute to the early and accurate diagnosis of sepsis in the future.

Combining pathogen and host metagenomics for a better sepsis diagnostic.

Combining simultaneous host and pathogen metagenomic profiles in a cohort of hospitalized and critically ill patients allows for more accurate diagnosis of sepsis.

Accurate diagnosis of sepsis using a neural network: Pilot study using routine clinical variables

Background and objectivesSepsis is a severe infection that increases mortality risk and is one if the main causes of death in intensive care units. Accurate detection is key to successful interventions, but diagnosis of sepsis is complicated because the initial signs and symptoms are not specific. Biomarkers that have been proposed have low specificity and sensitivity, are expensive, and not available in every hospital. In this study, we propose the use of artificial intelligence in the form of a neural network to diagnose sepsis using only common laboratory tests and vital signs that are routine and widely available. MethodsA retrospective, cross sectional cohort of 113 patients from an intensive care unit, each with 48 routinely evaluated vital signs and biochemical parameters was used to train, validate and test a neural network with 48 inputs, 10 neurons in a single hidden layer and one output. The sensitivity and specificity of the neural network as a point sampled diagnostic test was calculated. ResultsAll but one case were correctly diagnosed by the neural network, with 91% sensitivity and 100% specificity in the validation data set, and 100% sensitivity and specificity in the test data set. ConclusionsThe designed neural network system can identify patients with sepsis, with minimal resources using standard laboratory tests widely available in most health care facilities. This should reduce the burden on the medical staff of a difficult diagnosis and should improve outcomes for patients with sepsis.

One-step-immunoassay of procalcitonin enables rapid and accurate diagnosis of bacterial infection.

Procalcitonin (PCT) (i.e. a precursor of calcitonin) attracts much attention as a reliable biomarker of bacterial infections because its concentration increases rapidly in the blood when bacterial infections occur in the body. Sepsis may occur due to indiscriminate and vigorous proliferation of infectious bacteria, and accordingly early diagnosis and treatment of bacterial infection are of crucial importance. However, current diagnostic methods for sepsis suffer from long assay time, multiple and complex assay steps, inaccuracy, and requirement of analytical equipments. The goal of this study is to develop an advanced one-step-immunoassay that enables quick and accurate diagnosis of sepsis through measuring the PCT concentration in patient sera, which is based on self-enhancement of optical detection signals from large gold particles (i.e. clusters of gold nanoparticles) that are formed on the agglomerates of PCT-bound 3-dimensional (3D) probes. The 3D probe is constructed through attaching polyclonal anti-PCT antibodies (IgGs) to the surface of a modified hepatitis B virus (HBV) capsid, where both tandem repeats of the B domain of Staphylococcal protein A (SPAB) and the hexa-histidine tag are inserted into each HBV core protein (i.e. subunit of HBV capsid). That is, anti-PCT IgGs are attached via strong interaction between the Fc region and surface-exposed SPAB. Furthermore, hook effect-free and PCT concentration-dependent optical signals were consistently generated by adding both bovine serum albumin (BSA) and nickel ions to patient sera and also by optimally adjusting the 3D probe concentration. Compared to conventional chemiluminescent microparticle immunoassay (CMIA) showing poor linearity of detection signals, this novel immunoassay accurately detected PCT with good linearity between PCT concentrations and optical signals in a wide range of PCT concentrations (0.05–200 ng mL−1) and also showed a sufficiently low limit of detection, resulting in 100% sensitivity and 100% specificity when tested with 30 sepsis patients and 30 healthy individuals.

Diagnostic value of procalcitonin and presepsin for sepsis in critically ill adult patients: a systematic review and meta-analysis

BackgroundEarly and accurate diagnosis of sepsis is challenging. Although procalcitonin and presepsin have been identified as potential biomarkers to differentiate between sepsis and other non-infectious causes of systemic inflammation, the diagnostic accuracy of these biomarkers remains controversial. Herein, we performed a comprehensive meta-analysis to assess the overall diagnostic value of procalcitonin and presepsin for the diagnosis of sepsis.MethodsWe searched three electronic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials) for relevant studies. Two authors independently screened articles on the basis of inclusion and exclusion criteria. The pooled sensitivity, specificity, and summary receiver operating characteristic curves were estimated. The quality of evidence for diagnostic accuracy in absolute effects, i.e., the number of true or false positives and true or false negatives, gave a particular pre-test probability.ResultsWe included 19 studies (19 observational studies and no randomized controlled trials) that had enrolled 3012 patients. Analyses of summary receiver operating characteristic curves revealed areas under the receiver operating characteristic curves of 0.84 for procalcitonin and 0.87 for presepsin. The pooled sensitivities and specificities were 0.80 (95% confidence interval 0.75 to 0.84) and 0.75 (95% confidence interval 0.67 to 0.81) for procalcitonin. For presepsin, these values were 0.84 (95% confidence interval 0.80 to 0.88) and 0.73 (95% confidence interval 0.61 to 0.82), respectively. There were no statistically significant differences in both pooled sensitivities (p = 0.48) and specificities (p = 0.57) between procalcitonin and presepsin.ConclusionOur meta-analysis provided evidence that the diagnostic accuracy of procalcitonin and presepsin in detecting infection was similar and that both are useful for early diagnosis of sepsis and subsequent reduction of mortality in critically ill adult patients.Systematic review registrationThe study was registered in PROSPERO under the registration number CRD42016035784.

The sensitivity and specificity of neutrophil lymphocyte count ratio in diagnosing sepsis patients at Dr. Saiful Anwar General Hospital, Malang, Indonesia

Background: Sepsis is the most severe manifestation of acute infection which can cause death in 30-50% of cases. Rapid and accurate diagnosis of sepsis is a challenge for clinicians and laboratories. Neutrophil Lymphocyte Count Ratio is a potential index to detect the occurrence of sepsis. This examination is easy, fast and cheap. Procalcitonin is currently widely used as a newer indicator in diagnosing pre-shock but is rarely done because of its cost. This study aims to compare the diagnostic value of Neutrophil Lymphocyte Count Ratio with procalcitonin as a marker in septicpatients.Method: A Case-control analytic research was conducted from March to June 2018. Examination of neutrophils and lymphocytes using Sysmex XN-1000 while procalcitonin examination used Elecsys BRAHMS PCT using ECLIA method. Diagnostic values are analyzed using the ROC curve, and the cut-off value is determined. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy are calculated with 2x2 tables.Result: The subjects of the study were 60 patients who hospitalized and examined for procalcitonin with 30 patients diagnosed based on clinical symptoms and SOFA score ≥ two by clinicians as sepsis patients and also 30 control patients. ROC analysis with procalcitonin cut-off values of 2,24 ng / mL obtained a sensitivity of 93%, specificity of 86,7%, PPV of 86,9%, and NPV of 92,4%.. At the cut-off value of Neutrophil Lymphocyte Count Ratio 5,06, there was a sensitivity of 80%, specificity of 76,7%, PPV of 76,9%, and NPV of 79,1%.Conclusion: Procalcitonin has a better diagnostic value than Neutrophil Lymphocyte Count Ratio in diagnosing sepsis.

Comparison Between Procalcitonin and Traditional Blood Biomarkers in Diagnosis of Sepsis in Iraqi Wounded Soldiers

Early diagnosis of sepsis is a very critical matter especially for soldiers in battle field; on the other hand, Procalcitonin is a new promising biomarker for fast and accurate diagnosis of sepsis. The aim of this study is to investigate the ability of Procalcitonin (PCT) to indicate sepsis earlier than blood culture and other traditional biomarkers and then get use of this in early diagnosis of sepsis.Procalcitonin concentration was measured in 44 sera of Iraqi wounded soldiers who were admitted to GHAZI AL-HARIRI Hospital for surgery, using ELISA kit of BioRay/USA, along with blood culture and other infection biomarker like C-reactive protein, ESR, W.B.C. count. Six patients had elevated PCT and 3 of them had positive blood culture, two of these three died. PCT has good correlation with other inflammatory biomarkers. It is our recommendation to accredit PCT as a very early biomarker of sepsis in Iraqi hospitals along with blood culture but earlier than it, and to use the quick test of PCT in battlefield to determine the priority of transmission of wounded soldiers to hospitals.

Presepsin as a Novel Diagnostic Marker in Neonatal Septicemia

Background: Neonatal septicemia is a serious life-threatening condition with high mortality. The accurate diagnosis of sepsis is one of the main challenges in emergency medicine. A great effort to reduce the neonatal mortality rate is put into looking for new reliable biomarkers. Among biomarkers, presepsin could be one of the most promising and reliable biomarker for early diagnosis of sepsis. Objective: We aimed to evaluate the diagnostic value ofpresepsin in the early diagnosis of neonatal sepsis. Methodology: By chemiluminescent enzyme immunoassay (CLEIA), the level of presepsin was assessed in 40 full term neonates with suspected sepsis (Proven sepsis group: 23 patients with +ve blood culture & Probable sepsis group: 17 patients with -ve blood culture) and15 healthy full term neonates. Results: Presepsin level was found to be significantly higher in patient group than control group as well as in proven sepsis group than probable sepsis group. The cut off value for presepsin was 875pg/ml at which the sensitivity and specificity of presepsin were (95.7%, 87.5%) respectively. Presepsin level was found to be significantly higher in females than males. There was no significant difference in the presepsin level as regard mode of delivery nor onset of sepsis. Conclusion: Presepsin is a novel biomarker with high sensitivity and good specificity for sepsis and its measurement can be useful for early diagnosis of neonatal sepsis.

A new marker of sepsis post burn injury?*.

Accurate diagnosis of sepsis is difficult in patients post burn due to the large inflammatory response produced by the major insult. We aimed to estimate the values of serum N-terminal pro-B-type natriuretic peptide and procalcitonin and the changes in hemodynamic variables as markers of sepsis in critically ill burn patients. Prospective, observational study. A quaternary-level university-affiliated ICU. Fifty-four patients with burns to total body surface area of greater than or equal to 15%, intubated with no previous cardiovascular comorbidities, were enrolled. At admission, a FloTrac/Vigileo system was attached and daily blood samples taken from the arterial catheter. Infection surveillance was carried out daily with patients classified as septic/nonseptic according to American Burns Consensus criteria. N-terminal pro-B-type natriuretic peptide, procalcitonin, and waveform analysis of changes in stroke volume index and systemic vascular resistance index were measured within the first 24 hours after burn and daily thereafter for the length of the ICU stay or until their first episode of sepsis. Prevalences of stroke volume variation less than 12% (normovolemia) with hypotension (systolic blood pressure < 90 mm Hg) were recorded. Patients with sepsis differed significantly from "no sepsis" for N-terminal pro-B-type natriuretic peptide, systemic vascular resistance index, and stroke volume index on days 3-7. Procalcitonin did not differ between sepsis and "no sepsis" except for day 3. Area under the receiver operating characteristic curves showed excellent discriminative power for B-type natriuretic peptide (p = 0.001; 95% CI, 0.99-1.00), systemic vascular resistance index (p < 0.001; 95% CI, 0.97-0.99), and stroke volume index (p < 0.01; 95% CI, 0.96-0.99) in predicting sepsis but not for procalcitonin (not significant; 95% CI, 0.29-0.46). A chi-square crosstab found that there was no relationship between hypotension with normovolemia (stroke volume variation < 12%) and sepsis. Serum N-terminal pro-B-type natriuretic peptide levels and certain hemodynamic changes can be used as an early indicator of sepsis in patients with burn injury. Procalcitonin did not assist in the early diagnosis of sepsis.

Serum procalcitonine levels as an early diagnostic indicator of sepsis.

Introduction:Prompt and accurate diagnosis of sepsis is of high importance for clinicians. Procalcitonine (PCT) and C-reactive protein (CRP) have been proposed as markers for this purpose. Our aim was to evaluate the levels of PCT and CRP in early sepsis and its correlation with severity of sepsis.Methods:Levels of PCT and CRP were taken from 60 patients with sepsis criteria and 39 patients with SIRS symptoms from the University Hospital Center “Mother Teresa” in Tirana, Albania during 2010-2012. Sensitivity, specificity and predictive values for PCT and CRP were calculated.Results:PCT and CRP levels increased in parallel with the severity of the clinical conditions of the patients. The mean PCT level in patients with sepsis was 11.28 ng/ml versus 0.272 ng/ml in patients with SIRS symptoms, with a sensitivity of 97.4% and a specificity of 96.6% for PCT >0.5ng/ml. The mean CRP level in septic patients was 146.58 mg/l vs. 34.4 mg/l in patients with SIRS, with a sensitivity of 98.6% for sepsis and a specificity of 75 % for CRP >11mg/l.Conclusion:PCT and CRP values are useful markers to determine early diagnosis and severity of an infection. In the present study, PCT was found to be a more accurate diagnostic parameter for differentiating SIRS from sepsis and may be helpful in the follow-up of critically ill patients.

Biomarkers for the differentiation of sepsis and SIRS: the need for the standardisation of diagnostic studies

Sepsis is a leading cause of death in the critically ill patient. It is a heterogeneous disease and it is frequently difficult to make an unequivocal and expeditious diagnosis. The current 'gold standard' in diagnosing sepsis is the blood culture but this is only available after a significant time delay. Mortality rates from sepsis remain high, however, the introduction of sepsis care bundles in its management has produced significant improvements in patient outcomes. Central to goal-directed resuscitation is the timely and accurate diagnosis of sepsis. The rapid diagnosis and commencement of the appropriate therapies has been shown to reduce the mortality. Biomarkers are already used in clinical practice to aid other more traditional diagnostic tests. In the absence of an adequate gold standard to diagnose sepsis, there has been considerable and growing interest in trying to identify suitable biomarkers. There is currently an unmet need in the medical literature to communicate the importance of the challenges relating to the rapid diagnosis and implementation of goal-directed therapy in sepsis and the underlying concepts that are directing these investigations. This article reviews the more novel biomarkers investigated to differentiate systemic inflammatory response syndrome from sepsis. The biomarkers described reflect the difficulties in making evidence-based recommendations particularly when interpreting studies where the methodology is of poor quality and the results are conflicting. We are reminded of our responsibilities to ensure high quality and standardised study design as articulated by the STAndards for the Reporting of Diagnostic accuracy studies (STARD) initiative.

SIC – a new hematologic parameter for early diagnosis of sepsis in preterm infants

Introduction: Early and accurate diagnosis of sepsis in preterm infants is vital. Despite intensive research in the field of early and reliable sepsis screening tests, no satisfactorily sensitive and specific parameter has been found so far. Aim: To evaluate a new hematologic parameter for the early diagnosis of nosocomial sepsis in preterm infants in comparison to interleukin-8 (IL-8). This new hematological parameter called „SIC“ (Single Infection and Control parameter) is calculated on the basis of the immature information (IMI) channel by the Sysmex XE-2100 blood analyzer which represents information regarding immature blood cells after selective lyses of leukocytes. The parameter is gained automatically and simultaneously by routine blood count measurement which requires neither additional blood sampling from the patient nor an increased volume of blood. Methods: Twenty-five preterm infants below 32 weeks' of gestation with culture-positive nosocomial sepsis were compared to 49 controls of same gestational age. A ROC plot was calculated with regard to SIC and IL-8. Results: Adopting a cut-off of 1.07at the time of clinical sepsis suspicion, the following values for SIC were calculated: sensitivity 76,9%, specificity 87.7%, PPV 55,6 and NPV 95. For IL-8 with a cut-off of 70pg/ml, the respective values were: 60%, 72,4%, 30, and 90,2. The area under the ROC plot was greater for SIC than for IL-8 (SIC: 0.834 and IL-8 0.693). Conclusion: Based on the overall shape of the two ROC plots, the SIC test appeared to be superior to IL-8 for diagnosis of nosocomial bacterial sepsis in preterm infants. A prospective study for evaluation of the new parameter in a higher number of patients is in progress.