Presepsin in Critical Illness: Current Knowledge and Future Perspectives.

The accurate identification of infections is critical for effective treatment in intensive care units (ICUs), yet current diagnostic methods face limitations in sensitivity and specificity, alongside cost and accessibility issues. Consequently, there is a pressing need for a marker that is economically feasible, rapid, and reliable. Presepsin (PSP), also known as soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for early sepsis diagnosis. PSP, derived from soluble CD14, reflects the activation of monocytes/macrophages in response to bacterial infections. It has shown potential as a marker of cellular immune response activation against pathogens, with plasma concentrations increasing during bacterial infections and decreasing post-antibiotic treatment. Unlike traditional markers such as procalcitonin (PCT) and C-reactive protein (CRP), PSP specifically indicates monocyte/macrophage activation. Limited studies in critical illness have explored PSP's role in sepsis, and its diagnostic accuracy varies with threshold values, impacting sensitivity and specificity. Recent meta-analyses suggest PSP's diagnostic potential for sepsis, yet its standalone effectiveness in ICU infection management remains uncertain. This review provides a comprehensive overview of PSP's utility in ICU settings, including its diagnostic accuracy, prognostic value, therapeutic implications, challenges, and future directions.

A Secondary Retrospective Analysis of the Predictive Value of Neutrophil-Reactive Intensity (NEUT-RI) in Septic and Non-Septic Patients in Intensive Care.

BACKGROUND: Effective identification and management in the early stages of sepsis are critical for achieving positive outcomes. In this context, neutrophil-reactive intensity (NEUT-RI) emerges as a promising and easily interpretable parameter. This study aimed to assess the predictive value of NEUT-RI in diagnosing sepsis and to evaluate its prognostic significance in distinguishing 28-day mortality outcomes. MATERIALS: This study is a secondary, retrospective, observational analysis. Clinical data upon ICU admission were collected. We enrolled septic patients and a control group of critically ill patients without sepsis criteria. The patients were divided into subgroups based on renal function for biomarker evaluation with 28-day outcomes reported for septic and non-septic patients. RESULTS: A total of 200 patients were included in this study. A significant difference between the "septic" and "non-septic" groups was detected in the NEUT-RI plasma concentration (53.80 [49.65-59.05] vs. 48.00 [46.00-49.90] FI, p < 0.001, respectively). NEUT-RI and procalcitonin (PCT) distinguished between not complicated sepsis and septic shock (PCT 1.71 [0.42-12.09] vs. 32.59 [8.83-100.00], <0.001 and NEUT-RI 51.50 [47.80-56.30] vs. 56.20 [52.30-61.92], p = 0.005). NEUT-RI, PCT, and CRP values were significantly different in patients with "renal failure". NEUT-RI and PCT at admission in the ICU in the septic group were higher in patients who died (58.80 [53.85-73.10] vs. 53.05 [48.90-57.22], p = 0.005 and 39.56 [17.39-83.72] vs. 3.22 [0.59-32.32], p = 0.002, respectively). Both NEUT-RI and PCT showed a high negative predictive value and low positive predictive value. CONCLUSIONS: The inflammatory biomarkers assessed in this study offer valuable support in the early diagnosis of sepsis and could have a possible role in anticipating the outcome. NEUT-RI elevation appears particularly promising for early sepsis detection and severity discrimination upon admission.

The Potential Role of Neutrophil-Reactive Intensity (NEUT-RI) in the Diagnosis of Sepsis in Critically Ill Patients: A Retrospective Cohort Study.

The diagnosis of sepsis is often difficult and belated, substantially increasing mortality in affected patients. Its early identification allows for us to choose the most appropriate therapies in the shortest time, improving patients' outcomes and eventually their survival. Since neutrophil activation is an indicator of an early innate immune response, the aim of the study was to evaluate the role of Neutrophil-Reactive Intensity (NEUT-RI), which is an indicator of their metabolic activity, in the diagnosis of sepsis. Data from 96 patients consecutively admitted to the Intensive Care Unit (ICU) were retrospectively analyzed (46 patients with and 50 without sepsis). Patients with sepsis were further divided between sepsis and septic shock according to the severity of the illness. Patients were subsequently classified according to renal function. For the diagnosis of sepsis, NEUT-RI showed an AUC of >0.80 and a better negative predictive value than Procalcitonin (PCT) and C-reactive protein (CRP) (87.4% vs. 83.9% and 86.6%, p = 0.038). Unlike PCT and CRP, NEUT-RI did not show a significant difference within the "septic" group between patients with normal renal function and those with renal failure (p = 0.739). Similar results were observed among the "non-septic" group (p = 0.182). The increase in NEUT-RI values could be useful in the early ruling-out of sepsis, and it does not appear to be influenced by renal failure. However, NEUT-RI has not proved to be efficient in discriminating the severity of sepsis at the time of admission. Larger, prospective studies are needed to confirm these results.

Comparison of Freelite and N-Latex serum free light chain assays: a critical review.

INTRODUCTION: The measurement of serum free light chain (FLC) represents a fundamental aspect on the assessment of patients with monoclonal gammopathies (MG). Different analytical methods for FLC have become available with the possibility to obtain different value with a substantial impact on the assessment of patients with MG. This study aimed to evaluate FLC results obtained with two different assays and how the difference value obtained can impact in the patient's assessment. MATERIALS AND METHODS: Ninety-three patient serum samples that underwent analysis for FLC with two different methods, Serum Freelite (The Binding Site, Birmingham, UK) and N-Latex FLC (Siemens, Marburg, Germany), were included in this retrospective study. Statistical analysis was performed to evaluate correlation, difference, and the grade of concordance between the results obtained with the two methods. RESULTS: Significant statistical differences between the results obtained from the two methods were found (P < 0.05). A good correlation was found (0.99 for κ FLC, 0.95 for λ FLC, and 0.94 for the κ/λ ratio, respectively). We found a weighted kappa value of 0.65 for κ/λ ratio, 0.65 for λ FLC and 0.90 for κ FLC. A positive bias found with the Bland-Altman plot mirrors overestimation of κ FLC and κ/λ ratio with Freelite compared to N-Latex, whilst a negative bias underscores underestimation of λ FLC by Freelite compared to N-Latex. CONCLUSION: Although in general the concordance between Freelite and N-Latex appears satisfactory, several discrepancies could be evidenced and consequently the two assays are not interchangeable.

Use of the reticulocyte channel warmed to 41 °C of the XN-9000 analyzer in samples with the presence of cold agglutinins

ABSTRACT Objectives The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) < 370 g/L and in samples with the MCHC > 370 g/L, in the presence of cold agglutinins. Methods In this study, 60 blood samples (group 1) with the MCHC < 370 g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC > 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

Use of the reticulocyte channel warmed to 41°C of the XN-9000 analyzer in samples with the presence of cold agglutinins.

OBJECTIVES: The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41°C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC)<370g/L and in samples with the MCHC>370g/L, in the presence of cold agglutinins. METHODS: In this study, 60 blood samples (group 1) with the MCHC<370g/L (without cold agglutinins) and 78 blood samples (group 2) with the MCHC>370g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). RESULTS: The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. CONCLUSIONS: The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370g/L.

Preliminary assessment of the new Sysmex XN parameter Iron-Def for identifying iron deficiency.

BACKGROUND: Although the clinical assessment of iron status is usually based on iron stores, a rapid and accurate diagnosis of iron deficiency is challenging since ferritin is often unavailable as an urgent test and its value is frequently increased in acute phase conditions. This study was therefore aimed at evaluating the diagnostic performance of the new Sysmex XN "Iron Deficiency?" (Iron-Def) parameter for identifying patients with iron deficiency. MATERIALS AND METHODS: The study population consisted of 688 consecutive patients (median age: 71 years; 341 women and 347 men), referred for routine diagnostics to the Laboratory of Clinical Pathology of Lecco Hospital, Italy. A complete clinical chemistry profile and haematological testing were performed for identifying iron deficiency anaemia. RESULTS: A significant negative correlation was found between Sysmex XN Iron-Def and ferritin, serum iron, mean cell haemoglobin concentration, mean cell haemoglobin, mean corpuscular volume and age, while a positive correlation was noted with transferrin, percentage of microcytic red cell, red blood cell count and red blood cell distribution width. The diagnostic accuracy of Iron-Def for identifying patients with a percentage of saturation of transferrin <15% (n=104) was 84%, with a sensitivity of 0.952 and specificity of 0.538. A sub-analysis of 71 patients with ferritin <20 ng/dL yielded an even better diagnostic performance (86%, with a sensitivity of 0.935 and specificity of 0.620). DISCUSSION: Although additional confirmatory investigations would be needed, the preliminary findings of our study attest that Iron-Def may be an easy, inexpensive, rapid and reliable parameter for screening iron deficiency anaemia.

The impact of different sample matrices in delayed measurement of glucose.

OBJECTIVES: This study was designed to compare glucose values in serum or lithium-heparin samples immediately centrifuged with those paired specimens collected in tubes containing Naf-KOx and centrifuged and analyzed 2.5h after collection. METHODS: Three blood samples were drawn from 20 volunteers. Blood samples collected in tubes with and clot activator and gel separator but without anticoagulant (SST) as well as those collected in tubes containing Lithium-Heparin and gel separator were centrifuged within 30min and analyzed 2h thereafter. Blood samples drawn in tubes containing the glycolysis inhibitor NaF-KOx were centrifuged after 2.5h and then analyzed. RESULTS: The glucose median value was 4.72mmol/L in SST tubes, 4.67mmol/L in lithium-heparin and 4.44mmol/L in NaF-KOx tubes. The difference between SST and lithium-heparin tubes was not statistically or clinically significant, whereas that between SST and Naf-KOx tubes was both analytically and clinically meaningful, exceeding the current quality specifications for glucose measurement. CONCLUSIONS: The rapid centrifugation of blood collected in serum or lithium-heparin tubes with gel separator is seemingly more reliable for delayed measurement of glucose compared to the use of blood tubes containing NaF-KOx.

Spurious elevation of serum potassium concentration measured in samples with thrombocytosis.

BACKGROUND: Several factors that can lead to falsely elevated values of serum. Thrombocytosis is one of these factors, since breakage or activation of platelets during blood coagulation in vitro may lead to spurious release of potassium. The purpose of the study was to evaluate to which extent the platelet count may impact on potassium in both serum and plasma. METHODS: The study population consisted of 42 subjects with platelets values comprised between 20 and 750×109/L. In each sample potassium was measured in both serum and plasma using potentiometric indirect method on the analyzer Modular P800 (Roche, Milan, Italy). Platelet count was performed with the hematological analyzer Advia 120 (Siemens, Milano, Italy). RESULTS: Significant differences were found between potassium values in serum and in plasma. A significant correlation was also observed between serum potassium values and the platelet count in whole blood, but not with the age, sex, erythrocyte and leukocyte counts in whole blood. No similar correlation was noticed between plasma potassium and platelet count in whole blood. The frequency of hyperkalemia was also found to be higher in serum (20%) than in plasma (7%) in samples with a platelet count in whole blood >450×109/L. CONCLUSIONS: The results of this study show that platelets in the biological samples may impact on potassium measurement when exceeding 450×109/L. We henceforth suggest that potassium measurement in plasma may be more accurate than in serum, especially in subjects with thrombocytosis.