Presepsin Research Articles

Presepsin Does Not Predict Risk of Death in Sepsis Patients Admitted to the Intensive Care Unit: A Prospective Single-Center Study.

Background: Sepsis is defined as life-threatening organ dysfunction caused by an abnormal host response to infection. The study aimed to evaluate the utility of presepsin (P-SEP) in predicting the risk of death in patients with sepsis at the time of intensive care unit (ICU) admission. Methods: Adult patients were included in the study if they met SEPSIS-3 criteria at ICU admission. Demographic and clinical data were collected. The following inflammatory parameters were determined: C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and presepsin (P-SEP). Material was collected for microbiological testing depending on the suspected source of infection. The primary endpoint was patient death before ICU discharge. The secondary endpoint was a positive microbiological test result. Results: Eighty-six patients were included in the study. Thirty patients (35%) died before discharge from the ICU. There was no difference in P-SEP, CRP, PCT, and IL-6 values between patients who survived and those who died (p > 0.05 for all). P-SEP, CRP, PCT, and IL-6 were determined at ICU admission and did not accurately predict the risk of death in ROC curve analysis (p > 0.05 for all). Confirmation of the location of the focus of bacterial infection by microbiological testing was obtained in 43 (49%) patients. P-SEP, PCT, CRP, and IL-6 were significantly higher in patients with positive microbiological findings. Conclusions: In patients with suspected sepsis admitted to the Intensive Care Unit, presepsin does not accurately predict the risk of in-hospital death, but it can predict a positive microbiological culture.

Early Fever in Allogeneic Stem Cell Transplantation: Are Presepsin and YKL-40 Valuable Diagnostic Tools?

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving treatment but carries a high infection risk. Diagnosing infections remains challenging due to the limited accuracy of standard biomarkers. Methods: This single-center study aimed to evaluate presepsin (PSP) and YKL-40 as infection biomarkers in febrile patients during the allo-HSCT pre-engraftment phase. Biomarker levels were prospectively measured in 61 febrile episodes from 54 allo-HSCT patients at admission, representing baseline levels, and then at Day 1, 3, 5, and 7 following fever onset. The diagnostic value was compared to that of procalcitonin (PCT). Results: PSP showed fair diagnostic value on Day 1 (AUC 0.656; 95% CI: 0.510-0.802) and Day 3 (AUC 0.698; 95% CI: 0.559-0.837). YKL-40 did not provide any significant diagnostic value across measured time points. PCT outperformed PSP and YKL-40, particularly on Day 3 (AUC 0.712; 95% CI: 0.572-0.852). When combining biomarkers, the best model for predicting infection used PSP > 3.144 ng/mL and PCT > 0.28 μg/L on Day 3, resulting in R2 of about 31% (p < 0.001). Conclusions: Neither test showed sufficient discriminative power for early infection to recommend their use as individual diagnostic tools in clinical practice.

Features of Metabolites and Biomarkers in Inflammatory and Infectious Complications of Childhood Cancers.

Background: In the treatment of oncological diseases in children, the search for opportunities for the earlier detection of complications to improve treatment results is very important. Metabolomic studies are actively conducted to stratify different groups of patients in order to identify the most promising markers. Methods: Three groups of patients participated in this study: healthy children as a control group (n = 18), children with various malignant oncological diseases (leukemia, lymphoma, nephroblastoma, ependymoma, etc.) as patients (n = 40) without complications, and patients (n = 31) with complications (inflammatory and infectious). The mitochondrial metabolites (succinic and fumaric acids); biomarkers related to inflammation such as C-reactive protein (CRP), procalcitonin (PCT), and presepsin (PSP); and sepsis-associated aromatic metabolites, such as phenyllactic (PhLA), hydroxyphenyllactic (p-HPhLA), and hydroxyphenylacetic acids (p-HPhAA), were identified. Results: It was found that children with malignant oncological diseases had profound metabolic dysfunction compared to healthy children, regardless of the presence of systemic inflammatory response syndrome (SIRS) or sepsis. The prognostic ability of procalcitonin and presepsin for detecting sepsis was high: AUROC = 0.875, cut-off value (Youden index) = 0.913 ng/mL, and AUROC = 0.774, with cut-off value (Youden index) of 526 pg/mL, respectively. Conclusions: A significant increase in aromatic microbial metabolites and biomarkers in non-survivor patients that is registered already in the first days of the development of complications indicates the appropriateness of assessing metabolic dysfunction for its timely targeted correction.

Presepsin in Human Milk Is Delivery Mode and Gender Dependent.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case-control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at -80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

Identification of organs of origin of macrophages that produce presepsin via neutrophil extracellular trap phagocytosis

Presepsin (P-SEP) is a specific biomarker for sepsis. Monocytes produce P-SEP by phagocytosing neutrophil extracellular traps (NETs). Herein, we investigated whether M1 macrophages (M1 MΦs) are the primary producers of P-SEP after NET phagocytosis. We co-cultured M1 MΦs and NETs from healthy participants, measured P-SEP levels in the culture medium supernatant, and detected P-SEP using western blotting. When NETs were co-cultured with M1 MΦs, the P-SEP level of the culture supernatant was high. Notably, we demonstrated, for the first time, the intracellular kinetics of P-SEP production by M1 MΦs via NET phagocytosis: M1 MΦs produced P-SEP intracellularly 15 min after NET phagocytosis and then released it extracellularly. In a sepsis mouse model, the blood NET ratio and P-SEP levels, detected using ELISA, were significantly increased (p < 0.0001). Intracellular P-SEP analysis via flow cytometry demonstrated that lung, liver, and kidney MΦs produced large amounts of P-SEP. Therefore, we identified these organs as the origin of M1 MΦs that produce P-SEP during sepsis. Our data indicate that the P-SEP level reflects the trend of NETs, suggesting that monitoring P-SEP can be used to both assess NET-induced organ damage in the lungs, liver, and kidneys during sepsis and determine treatment efficacy.

The Diagnostic and Prognostic Values of Soluble CD14 Subtype (Presepsin) in Early Detection of Early Onset Neonatal Sepsis in Preterm Newborns

Abstract Background The diagnosis of “suspected sepsis” in neonates in the NICU is one of the most common and challenging diagnoses due to the nonspecific signs of sepsis. therefore, laboratory investigation is necessary in cases of doubt or if there are risk factors. A promising biomarker: Presepsin (P-SEP), or Soluble Cluster of Differentiation 14 Subtype (sCD14-ST) is generated as a part of the body’s response to bacterial infection. It is effective in the early phase of inflammation, and it is detected as an early marker of sepsis in neonates. Aim and Objectives to evaluate the diagnostic value of presepsin in early neonatal sepsis and prognostic value for severity, mortality and hospital stay length. Subjects and Methods This prospective observational study include two groups, one group included 36 neonates with risk factors for early-onset sepsis, along with 20 uninfected neonates as the control group. Both groups were subjected to the calculation of Rodwell score, SNAP II score, serum presepsin levels, CRP measurement, and blood culture and assessed for clinical severity, mortality, and hospital stay length. Result Serum baseline presepsin was significantly elevated in sepsis group (P &amp;lt; 0.001), Presepsin showed the best diagnostic performance over Rodwell score (AUC 0.989; sensitivity of 93.8% and specificity of 95%). Presepsin levels on day 3 were significantly elevated in non-survived patients (P &amp;lt; 0.001), with better predictive performance for 28-day mortality and rapid progression to death than SNAP II score (AUC 0.880; sensitivity of 83.3% and specificity of 87.5%). Conclusion presepsin day 1 was useful diagnostic tools in culture proven early onset neonatal sepsis, presepsin at day 3 could be a good predictor for gram negative infections, 28-day mortality, and sepsis severity.

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.

Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit.

In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay. We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis. MDW, PCT, CRP, and PSP were evaluated at admission (T0), after 24 h (T24), 48 h (T48), 72 h (T72), at day 5 (T5), and at discharge (TD). Patients with sepsis displayed higher levels of PCT and PSP than patients without sepsis at each timepoint; differently, CRP displayed statistically significant differences only at T0, while MDW only at T0 and T24. Patients with increasing levels of PSP displayed lower median survival time than patients with decreasing levels; differences reached statistical significance only at 48 h (20 vs. 29 days, log rank test, p = 0.046). Interestingly, PSP was an independent predictor of ICU mortality at 48 and 72 h after hospital admission. Also, the kinetic of PSP had prognostic value, with increased values at 48 h after admission being associated with reduced survival. Our findings support the role of PSP and its kinetic as a predictor of ICU mortality.

Presepsin Levels in Pediatric Patients with Fever and Suspected Sepsis: A Pilot Study in an Emergency Department.

Sepsis is a life-threatening condition that affects 1.2 million children annually. Although there are several criteria for diagnosing this condition, signs are often nonspecific, and identifying sepsis is challenging. In this context, presepsin (P-SEP) seems to be a promising new biomarker since its plasma levels increase earlier than other sepsis-related proteins and its measurement is faster. We enrolled 157 minors who presented to the Pediatric Emergency Department of Agostino Gemelli Hospital with fever and suspected sepsis. Biochemical, anamnestic, and clinical data were collected. Viral agents were identified as the causative factor in 64 patients, who had an average P-SEP value of 309.04 pg/mL (SD ± 273.2), versus an average P-SEP value of 526.09 pg/mL (SD ± 657) found in 27 bacterial cases (p value: 0.0398). Four cases of overt sepsis had an average P-SEP value of 3328.5 pg/mL (SD ± 1586.6). The difference in P-SEP levels in viral versus bacterial infections was found to be statistically significant; therefore, P-SEP may have a central role in the evaluation of febrile children, helping clinicians distinguish between these two etiologies. Furthermore, amongst the cases of confirmed sepsis, P-SEP was always greater than 2000 pg/mL, while C-reactive protein and procalcitonin values appeared lower than what was considered significant.

Combined estimation of presepsin and gelsolin might improve the diagnostic validity of clinical scoring to predict and stratify sepsis in non-sepsis surgical ICU patient

ABSTRACT Objectives This study evaluates the ability of serum presepsin (PSEP) and gelsolin (GSN) levels estimated in blood samples obtained at the admission of sepsis-free patients to surgical ICU (SICU) as early predictors for getting sepsis and sepsis-related complications. Patients & Methods 260 sepsis-free trauma and postoperative patients who were admitted to SICU were clinically evaluated. At-admission blood samples were obtained for total and differential leucocytic counting and ELISA estimation of serum C-reactive protein (CRP), procalcitonin (PCT), PSEP and GSN, and PSEP/GSN ratio was calculated (PGR). Patients were observed for the SICU readmission rate after being ward-discharged for the sepsis rate and mortality rate (MR). Results The SICU readmission rate was 7.2%, the sepsis rate was 25.4%, and the sepsis-related MR was 5%. The estimated biomarkers were significantly higher in patients than negative controls but were lower than positive controls except serum levels of GSN that were significantly lower in patients’ samples than in negative, but higher than in positive controls. Statistical analyses defined high serum PSEP and lower serum GSN levels with high PGR as significant predictors for all the study outcomes. Conclusion Among sepsis-free patients who are admitted to SICU, getting septic complications is not an uncommon event and accounts for 5% of SICU mortalities. Estimated serum levels of PSEP and GSN might be valuable biomarkers for early distinguishing patients vulnerable to developing septic complications and predicting the possibility of non-surviving. The calculated PSEP/GSN ratio might be a collective early indicator for outcomes of patients admitted to SICU.

Fetal chronic hypoxia does not affect urinary presepsin levels in newborns at birth.

Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis.

Clinical significance of cerebrospinal fluid presepsin as adjunctive biomarker for postneurosurgical meningitis: A single-center prospective observational study.

Postneurosurgical meningitis (PNM) is a serious complication in neurocritical care patients, leading to clinical deterioration and worsening outcomes. Accurate diagnosis of PNM is often difficult due to the lack of definitive diagnostic criteria. This study investigates the potential utility of cerebrospinal fluid (CSF) presepsin (PSP), blood PSP, and the CSF/blood PSP ratio as adjunctive biomarkers for the diagnosis of PNM. We conducted a single-center prospective observational study at Nara Prefecture General Medical Center in Nara, Japan, from April 2020 to March 2022. The postoperative neurosurgical patients with suspected PNM were included in the study and divided into PNM and non-PNM groups. We evaluated the sensitivity, specificity, area under curves (AUCs), positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of PNM with CSF PSP, blood PSP, and CSF/blood PSP ratio compared in the two groups. We screened 241 consecutive patients with postoperative neurosurgery. Diagnosis of PNM was suspected in 27 patients, and the clinical diagnosis was confirmed in nine patients. The results of CSF PSP (cutoff: 736 pg/mL) for the diagnosis of PNM were sensitivity 89%, specificity 78%, PPV 67%, NPV 93%, AUC 0.81 (95% confidence interval [CI], 0.60-1.00), blood PSP (cut-off: 264 pg/mL) was 56%, 78%, 56%, and 78%, 0.65 (95% CI, 0.42-0.88), and those of CSF/blood PSP ratio (cutoff: 3.45) was 89%, 67%, 57%, and 92%, 0.83 (95% CI, 0.65-1.00). Elevated CSF PSP and CSF/blood PSP ratio may be associated with PNM and could serve as valuable adjunctive biomarkers for improving diagnostic accuracy.

Сравнительный анализ мониторинга биомаркеров воспаления у беременных с преждевременным разрывом плодных оболочек

Aim: to qualitatively improve the approach to timely detection of purulent septic compli-cations in pregnant women with a long anhydrous interval in the setting of prelabour rupture of membranes (PROM). Patients and Methods: this prospective single-center study involved 80 pregnant women at 32–34 weeks of gestation. Group 1 included 40 pregnant women with PROM and group 2 included 40 pregnant women with threatened preterm labor. Serum levels of presepsin (PSP), leukocyte count, and C-reactive protein (CRP) were measured at admission and after 24 and 48 hours. A somatic, gynecological, and obstetric history was also studied Results: pregnant women with PROM exhibited an aggravated somatic, gynecological, and obstetric history, which could be a prerequisite for purulent septic complications. Elevated PSP levels (≥300 pg/mL) were observed in 23 (57.5%) women in group 1 and 2 (5%) women in group 2. Chorioamnionitis developed in 7 (17.5%) women in group 1 with PSP levels ≥500 pg/mL and two or more clinical signs. Leukocytosis and elevated CRP were detected in 3 (7.5%) and 5 (21.7%) women, respectively. No cases of postpartum endometritis were reported. Mean-while, in group 1, partial abdominal wound dehiscence after C-section was found in 4 of 11 (36.4%) women and partial perineal wound dehiscence was found in 2 of 40 (5%) women. All complications were observed in women with high PSP at admission. No complications were de-tected in group 2. Conclusion: elevated PSP can be considered as a predictor for purulent septic complica-tions in women with PROM. This marker can be used as an additional criterion for revising treatment and choosing term and mode of delivery. PSP level reflects early manifestations of pu-rulent septic complications more quickly than CRP level and leukocyte count. KEYWORDS: prelabour rupture of membranes, preterm birth, chorioamnionitis, markers of inflammation, presepsin, C-reactive protein, strategy FOR CITATION: Kondratyuk D.V., Sulima A.N., Babich T.Yu. Comparative analysis of the monitoring of inflammatory biomarkers in pregnant women with prelabour rupture of membranes. Russian Journal of Woman and Child Health. 2024;7(2):150–154 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-10.

ПРОГНОЗИРОВАНИЕ ПЕРСИСТИРУЮЩЕГО ПЕРИТОНИТА В ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ

Objective: Improve the treatment results of patients with diffuse peritonitis by accurately predicting the progression of persistent peritonitis to septic shock in the postoperative period Methods: The study involved 75 patients with diffuse peritonitis. These patients were split into two groups based on whether their peritonitis persisted after surgery and if they needed further surgery. The study used pre- and intraoperative clinical and laboratory predictors to determine the progression of peritonitis to septic shock Results: The preoperative CT attenuation coefficient of intraperitoneal fluid, measured in Hounsfield units (HU), was significantly higher in the study group compared to the control group (28.35 HU vs. 18.3 HU; p&lt;0.001). The scores on the Mannheim Peritonitis Index (MPI) were also significantly higher in the study group compared to the control group (25 versus 16; p&lt;0.001). Additionally, the levels of presepsin (PSEP), procalcitonin (PCT), and C-reactive protein (CRP) were higher in the study group compared to the control group (p&lt;0.001): 1149.1 (153.7-2591) pg/ml, 12.7815 (4.286-22.557) ng/ml, and 232.5 (162.2-312.4) mg/l in the study group, and 410.3 (56.1-980.9) pg/ml, 3.087 (0.995-13.399) ng/ml, and 120.8 (25.7-280) mg/l in the control group, respectively Conclusion: The proposed method for predicting the progression of peritonitis to septic shock is based on the MPI score and the CT attenuation coefficient of intraperitoneal fluid, in combination with biomarkers of inflammation such as PSEP, PCT, and CRP. This method allows practical surgeons to recognize persistent peritonitis, be prepared for the deterioration of a patient's condition with the progression of persistent peritonitis to septic shock, and perform a timely and appropriate surgical intervention Keywords: Persistent peritonitis, tertiary peritonitis, Hounsfield unit, inflammatory markers.

Advances of presepsin in sepsis-associated ARDS.

This article reviews the correlation between presepsin and sepsis and the resulting acute respiratory distress syndrome (ARDS). ARDS is a severe complication of sepsis. Despite the successful application of protective mechanical ventilation, restrictive fluid therapy, and neuromuscular blockade, which have effectively reduced the morbidity and mortality associated with ARDS, the mortality rate among patients with sepsis-associated ARDS remains notably high. The challenge lies in the prediction of ARDS onset and the timely implementation of intervention strategies. Recent studies have demonstrated significant variations in presepsin (PSEP) levels between patients with sepsis and those without, particularly in the context of ARDS. Moreover, these studies have revealed substantially elevated PSEP levels in patients with sepsis-associated ARDS compared to those with nonsepsis-associated ARDS. Consequently, PSEP emerges as a valuable biomarker for identifying patients with an increased risk of sepsis-associated ARDS and to predict in-hospital mortality.

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.

Study of inflammatory markers and their diagnostic effectiveness in patients with COVID-19 patients

The study examines the relationship between the levels of laboratory serum markers of inflammation and severity in patients with COVID-19. The purpose of the study. To investigate the mechanisms of interaction of inflammatory markers and calculate their diagnostic effectiveness in patients with COVID-19 in assessing the severity and prognosis of the disease. Materials and methods. We conducted a retrospective cohort study of the blood of 104 patients aged 20–84 years admitted to the hospital. The patients were divided into groups: group 1 – mild degree (n = 14); group 2 – moderate degree (n = 50); group 3 – severe degree (n = 40). The concentration of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), presepsin (PSP), proadrenomedullin (MRpro-ADM), ferritin (F), components of the complement system C 3, C 4 were determined using original reagent kits on automated systems. Results. In the obtained results of primary studies in the general group, an increase in the average values of inflammatory markers from reference values was noted. Correlation analysis revealed reliable direct medium and weak connections between markers of inflammation. Thresholdvalues were obtained when comparing groups with mild and moderate severity for MRpro-ADM, PCT, F, and in the group with moderate and severe severity for PCT, PSP, CRP and IL-6, above which we can talk about the transition of the disease to a moderate and severe degree of the disease, respectively. Conclusions. Determination of concentration and threshold values with parameters of diagnostic sensitivity of acute-phase markers of inflammation serves as an additional criterion for assessing the severity of the disease, prognosis, monitoring of treatment, but not specific diagnosis and allows you to understand the mechanisms of the immune system response.

Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0.

The clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll-like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute-on-chronic liver failure (ACLF). Patients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1year and evaluated predictors of ACLF. One hundred and seventy three patients with AD were included (median MELD: 18; CLIF-C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674ng/L vs. 310ng/L vs. 157ng/L; p<0.001). In patients with AD, Child-Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow-up, 52 patients developed ACLF (median time from recruitment: 66days). PSP, CLIF-C AD score, and Child-Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780-0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF-C AD <50, a PSP >674ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis. The Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD.

A-136 Usefulness of Presepsin and Thrombomodulin Measurements for Predicting COVID-19 Mortality

Abstract Background Coronavirus disease (COVID-19) is a novel infectious disease developed into a pandemic since early 2020, resulting in extensive morbidity and mortality globally. Therefore, it is important to identify biomarkers for predicting the severity and mortality of COVID-19. We focused on presepsin (P-SEP) and thrombomodulin (TM), which are biomarkers of sepsis and endothelial dysfunction, respectively. Some reports have already suggested that these biomarkers can be associated with COVID-19, however, most of them assessed blood P-SEP and TM levels using only a single day measurement. In addition, since both P-SEP and TM are excreted by the kidney, renal dysfunction should be considered when evaluating these levels. In this study, to evaluate the usefulness of P-SEP and TM for the prognosis and prediction of COVID-19 severity, we investigated the changes in these levels after admission with or without adjustment for creatinine (CRE) level in COVID-19 patients. Methods Samples were residual sera obtained from COVID-19 patients (n = 674) admitted to the TMDU Hospital. Serum P-SEP and TM levels were measured using the STACIA clinical assay system. Disease severity was classified as mild, moderate, 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 classified into survivors and non-survivors. This study was approved by the institutional research ethics committee (No. M2020-110). Results Since patients who received recombinant human TM treatment had abnormally high TM levels (&amp;gt; 1000 U/mL), data after administration were excluded from the analysis. P-SEP and TM levels during hospitalization were significantly correlated with CRE levels. In the correlation between P-SEP and CRE, the slope of the severe group was different from that of the non-severe group. When compared the data extracted within 5 days after admission (n = 183) among the three severity groups, CRE levels showed no significant difference among them. On the other hand, P-SEP and TM levels at admission were significantly higher in the severe group than those in the mild group, even after adjusting for CRE levels. In addition, there was no significant difference in the P-SEP levels between survivors and non-survivors, whereas TM levels were significantly higher in non-survivors than in survivors. Changes in the P-SEP levels at two time points (interval: 4.1 ± 2.2 days) were significantly different between survivors and non-survivors. The second measurement of TM levels were elevated in both groups from the first measurement at admission. Conclusion This study suggested that the elevation of P-SEP and TM levels in severe COVID-19 patients might not only fluctuate with renal dysfunction, but might reflect severity. TM and continuous P-SEP measurements are available for predicting mortality in patients with COVID-19. Moreover, P-SEP and TM values after CRE adjustment would be independent predictive markers, apart from renal function.

Physiologic postoperative presepsin kinetics following primary cementless total hip arthroplasty: A prospective observational study.

Presepsin is an emerging biomarker in the diagnosis of sepsis. In the field of orthopaedics, it could be useful in diagnosing and managing periprosthetic joint infections. To define the normal postoperative presepsin plasmatic curve, in patients undergoing primary cementless total hip arthroplasty (THA). Patients undergoing primary cementless THA at our Institute were recruited. Inclusion criteria were: Primary osteoarthritis of the hip; urinary catheter time of permanence < 24 h; peripheral venous cannulation time of permanence < 24 h; no postoperative homologous blood transfusion administration and hospital stay ≤ 8 d. Exclusion criteria were: The presence of other articular prosthetic replacement or bone fixation devices; chronic inflammatory diseases; chronic kidney diseases; history of recurrent infections or malignant neoplasms; previous surgery in the preceding 12 mo; diabetes mellitus; immunosuppressive drug or corticosteroid assumption. All the patients received the same antibiotic prophylaxis. All the THA were performed by the same surgical and anaesthesia team; total operative time was defined as the time taken from skin incision to completion of skin closure. At enrollment, anthropometric data, smocking status, osteoarthritis stage according to Kellgren and Lawrence, Harris Hip Score, drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS) and C-reactive protein 24 h before arthroplasty and at 24, 48, 72 and 96 h postoperatively and at 3, 6 and 12-mo follow-up. A total of 96 patients (51 female; 45 male; mean age = 65.74 ± 5.58) were recruited. The mean PS values were: 137.54 pg/mL at baseline, 192.08 pg/mL at 24 h post-op; 254.85 pg/mL at 48 h post-op; 259 pg/mL at 72 h post-op; 248.6 pg/mL at 96-h post-op; 140.52 pg/mL at 3-mo follow-up; 135.55 pg/mL at 6-mo follow-up and 130.11 pg/mL at 12-mo follow-up. In two patients (2.08%) a soft-tissue infection was observed; in these patients, higher levels (> 350 pg/mL) were recorded at 3-mo follow-up. The dosage of plasmatic PS concentration is highly recommended in patients undergoing THA before surgery to exclude the presence of an unknown infection. The PS plasmatic concentration should be also assessed at 72 h post-operatively, evaluate the maximum postoperative PS value, and at 96 h post-operatively when a decrease of presepsin should be found. The lack of a presepsin decrease at 96 h post-operatively could be a predictive factor of infection.