Procalcitonin Concentrations Research Articles

Immunosensor design based on Chitosan-QDs, a nanocomposite-modified electrode for selective procalcitonin sensing in clinic analyses

A simple free labeled electrochemical immunosensor based on chitosan (CHI) and quantum dots (QDs) was developed for the determination of procalcitonin (ProCT) antigen (Ag) which can act as a target biomarker of infectious diseases. The antibodies of the ProCT biomarker were successfully incubated on the CHI-QDs platform. Electrochemical impedance spectroscopy and cyclic voltammetry were used for the evaluation and characterization of various layers coated onto the electrode. Under the optimum conditions, the electron transfer resistance (Rct) of the immunosensor was altered linearly by the ProCT concentration. The proposed immunosensor was proportional to the ProCT biomarker concentration from 0.005 to 0.35ng/mL with a calculated detection limit of 0.015 pg/mL. The proposed biosensing device also exhibited high stability and reproducibility, which can be used for the quantitative assay of the ProCT biomarker in clinic analyses.

A novel computer vision-based assessment of neutrophil chemotaxis in patients with severe infection.

ObjectivesTo evaluate the value of chemotactic function of neutrophils in patients with severe infections.MethodsA computer vision‐based cellular chemotaxis analysis platform was established for the dynamic assessment of neutrophil chemotaxis. Fifty‐three patients in the intensive care unit were eligible for the study. In parallel, 142 healthy volunteers were recruited to detect and establish the normal values for chemotactic function. Four chemotactic function indicators were determined–chemotaxis distance (CD), chemotaxis cell ratio (CCR), chemotaxis index (CI) and maximum speed of chemotaxis (Vmax). The chemotaxis function scores (CFS) were calculated for further correlation analysis with clinical data.ResultsThe normal ranges of indicators were established as CD ≥ 1755.85 µm, CCR ≥ 3.34%, CI ≥ 39.63, Vmax ≥ 14.63 µm min−1 and CFS ≥ 15. We found that the chemotactic function of neutrophils in patients suffering from infections was significantly impaired. The mean values of CD, CCR, CI, Vmax and CFS were 1452.8 µm (P < 0.0001), 3.1% (P < 0.0001), 34.5 (P < 0.0001), 12.2 µm min−1 (P < 0.0001) and 9 (P < 0.0001), respectively. CD and CFS were significantly negatively correlated with the APACHE II score (rCD = −0.55, rCFS = −0.39), SOFA score (rCD = −0.68, rCFS = −0.56), procalcitonin concentration (rCD = −0.60, rCFS = −0.5) and the expression of P2RX1 (rCD = −0.76, rCFS = −0.56), respectively.ConclusionsCD, CCR, CI and Vmax can well reflect the neutrophil chemotactic function in patients with severe infections. CFS systematically indicated neutrophil function and has promising clinical application prospects.

Delta-Hemoglobin Equivalent and Granularity Index as Cell-Derived Biomarkers for the Detection of Bacterial Infections.

Prompt and precise detection of an infection in the blood is of great clinical importance in terms of early therapy initiation and the patient's prognosis. Infection-triggered inflammatory cellular and humoral signaling cascades offer great opportunities to redefine standard tests. However, while inexpensive and easy-to-use biomarkers for the detection of infections and the concomitant inflammatory processes exist, they are rarely used in clinical practice. We aimed to investigate the correlation of Granularity Index (GI) and Delta-hemoglobin equivalent (Delta-He) as inexpensive and easy-to-use cell-derived infection markers with established acute-phase parameters in a randomly selected patient. We analyzed plasma concentrations of the established C-reactive protein (CRP) and procalcitonin (PCT) and leukocyte and thrombocyte counts in blood samples of 1,787 patients undergoing routine laboratory inflammation diagnostics. We also measured the Granularity Index (GI) and Delta-hemoglobin equivalent (Delta-He) in this cohort between February 2019 and February 2020. Delta-He and GI Index significantly correlated with CRP concentration (AUC 0.72, 95% CI 0.71 - 0.74; p < 0.001 for both analytes) and thrombocyte count (p < 0.001 for both analytes) but not with leukocyte count (AUC 0.54, 95% CI 0.50 - 0.59, p < 0.67). Furthermore, Delta-He significantly correlated with PCT (AUC 0.65, 95% CI 0.63 - 0.68, p < 0.001) while GI Index did not. Additionally, thrombocyte count significantly correlated with CRP (p < 0.001) and with PCT concentrations (p < 0.001). Delta-He and GI are two novel, inexpensive and easy-to-use cell-derived hematological biomarkers with the potential to be used as fully automated and highly standardized parameters. These biomarkers would be available on a 24 hours basis in the routine laboratory for the detection of bacterial infections by measuring a complete blood count (CBC) with differential and reticulocyte counts.

Inflammation characteristics and anti-inflammation treatment with tocilizumab of severe/critical COVID-19 patients: A retrospective cohort study

The efficacy of tocilizumab on the prognosis of severe/critical COVID-19 patients is still controversial so far. We aimed to delineate the inflammation characteristics of severe/critical COVID-19 patients and determine the impact of tocilizumab on hospital mortality. Here, we performed a retrospective cohort study which enrolled 727 severe or critical inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Huoshenshan Hospital (Wuhan, China), among which 50 patients received tocilizumab. This study confirmed that most recovered patients manifested relatively normal inflammation levels at admission, whereas most of the deceased cases presented visibly severe inflammation at admission and even progressed into extremely aggravated inflammation before their deaths, proved by some extremely high concentrations of interleukin-6, procalcitonin, C-reactive protein and neutrophil count. Moreover, based on the Cox proportional-hazards models before or after propensity score matching, we demonstrated that tocilizumab treatment could lessen mortality by gradually alleviating excessive inflammation and meanwhile continuously enhancing the levels of lymphocytes within 14 days for severe/critical COVID-19 patients, indicating potential effectiveness for treating COVID-19.

A Diagnostic Platform for Rapid, Simultaneous Quantification of Procalcitonin and C-Reactive Protein in Human Serum

Background: Early and accurate determination of bacterial infections as a potential cause for a patient’s systemic inflammatory response is required for timely administration of appropriate treatment and antibiotic stewardship. Procalcitonin (PCT) and C-reactive protein (CRP) have both been used as biomarkers to differentiate bacterial infections from other causes in multiple studies, particularly in the context of sepsis. There is an urgent need to develop a platform for simultaneous quantification of PCT and CRP, to enable the potential use of these biomarkers at the point-of-care.: Methods: A multiplexed lateral flow assay (LFA) and a fluorescence optical reader were developed. Assay performance was validated by testing spiked antigens in the buffer, followed by a validation study comparing results with conventional assays (Roche Cobas e411 Elecsys PCT and Siemens ADVIA XPT CRP) in 25 archived remnant human serum samples. Findings: A correlation of 0·97 (P < 0·0001) was observed for PCT, and a correlation of 0·95 (P < 0·0001) was observed for CRP using direct patient samples. We also validated our platform’s ability to predict concentrations beyond the hook effect range for CRP accurately. Interpretation: A fluorescence reader-based duplex LFA for simultaneous quantification of PCT and CRP was developed and successfully validated with clinical samples. The rapid, portable, and low-cost nature of the platform offers potential for differentiation of bacterial and viral infections in emergency and low-resource settings at the point-of-care. Funding Information: NIH/NIBIB Award 1R01EB021331, and Academic Venture Fund from the Atkinson Center for a Sustainable Future at Cornell University. Declaration of Interests: The authors have no conflicts of interest to disclose related to this work. In the interest of full disclosure, David Erickson and Saurabh Mehta are founders and board members for a diagnostic start-up focused on measuring nutritional biomarkers at the point-of-care. Ethics Approval Statement: We acquired 25 remnant patient serum samples with known PCT and CRP concentrations from Weill Cornell Medicine (New York, NY, USA). These samples were approved for use by the Cornell Institutional Review Board (IRB 1706018345) used for assay validation.

Circulating nuclear factor-kappa B mediates cancer-associated inflammation in human breast and colon cancer.

BackgroundInflammation is recognized as a hallmark feature of cancer development and progression. The aim of our study was to investigate the significance of serum nuclear factor kappa-B (NF-κB) levels as a circulating marker in the monitoring of inflammation in breast and colon cancer; to show the relationship between NF-κB with inflammatory parameters as tumour necrosis factor-α (TNF-α), soluble TNF-related apoptosis-inducing ligand (sTRAIL), interleukin-6 (IL-6), pentraxin-3 (PTX-3), procalcitonin (PCT), and C-reactive protein (CRP) levels.MethodsSerum NF-κB, TNF-α, sTRAIL, IL-6, PTX-3, PCT, and serum CRP levels were measured using enzyme-linked immunosorbent assay (ELISA) in 40 patients with breast cancer, 40 patients with colon cancer and 30 healthy controls.ResultsThe serum NF-κB, TNF-α, IL-6, PTX-3, PCT, and serum CRP concentration was significantly higher, and the serum sTRAIL concentration was significantly lower in the patients with breast and colon cancer than in healthy controls. NF-κB was positively correlated with CRP and negatively correlated with sTRAIL.ConclusionsThese results suggest that increased NF-κB may decrease the clinical efficacy of sTRAIL in solid tumour cells. There is a relationship between inflammation and carcinogenesis so that the development of cancer occurs with chronic inflammation in breast and colon. The study results have shown that colon and breast cancer patients have increased systemic inflammation, as measured by increased circulating cytokines, and acute-phase proteins, or by abnormalities in circulating cells. NF-κB may combine with other markers of the systemic inflammatory response in prognostic scores in cancer. In addition to surgical resection of the tumour, and conventional radio and chemotherapy for cancer treatment, the use of sTRAIL or other agonists for cancer therapy appeared a new potential therapy.

The value of sepsis biomarkers and their kinetics in the prognosis of septic shock due to bacterial infections.

In this study, we aim to explore the value of procalcitonin (PCT), C-reactive protein (CRP), and serum cholinesterase (SChE) activity kinetics as useful predictors of mortality in patients with septic shock admitted to the intensive care unit (ICU). We conducted aprospective single-blinded study in the ICU of auniversity hospital during aperiod of 1 year. Were included all patients 18 years of age or older, with confirmed septic shock. For all included patients, blood samples of septic biomarkers (PCT, SChE activity, and CRP) were obtained. Serum was collected at the day of ICU admission (day 0), the day of septic shock (day 1), then 3 and 5 days after the septic shock development. During the study period, 60 patients were included. The mean age (± SD) was 47.7 ± 19 years. There were 46 male (74%) and 14 female (26%) patients. Mean SAPSII on ICU admission was 40.7 ± 16 (median: 37), and mean SOFA score on ICU admission was 16 ± 4 (median: 7). During their ICU stay, out of the 60 included patients, 37 patients died (61%). The comparison between the 2 groups (deaths and survivors) showed that the factors associated with poor outcome were age, SOFA score on ICU admission, and the need for invasive mechanical ventilation. The day of septic shock, there was no difference in the mean concentrations in those of plasma SChE activity or in the PCT and CRP plasma between survivors and non-survivors. However, the comparison of mean plasma SChE activity, and PCT and CRP plasma concentrations (on day 3 and day 5) between survivors and non-survivors, showed asignificant difference between the 2 groups. Our study suggests that, in agroup of critically ill patients with severe septic shock, arise or no change in procalcitonin and/or CRP level, and/or adecrease or no change in SChE activity should warn the clinician about the insufficiency and/or inadequacy of the therapy. However, afall in procalcitonin and/or CRP levels, and/or arise in SChE activity were associated with afavourable prognosis. Based on our study and some other data detailed above, we recommend that an estimation of SChE acti-vity, procalcitonin, and CRP on the day of septic shock, followed by estimation within the next 72-120 h, could help the prognostic assessment of critically ill patients with septic shock. Further studies are needed to define the critical values related to mortality.

The Level of Procalcitonin in Severe COVID-19 Patients: A Systematic Review and Meta-Analysis.

There is data from individual clinical trials suggesting that procalcitonin (PCT) may be a prognostic factor in the severity of COVID-19 disease. Therefore, this systematic review and meta-analysis was performed to investigate PCT levels in severe COVID-19 patients. We searched Embase, ProQuest, MEDLINE/PubMed, Scopus, and ISI/Web of Science for studies that reported the level of PCT of patient with severe COVID-19. We included all studies regardless of design that reported the level of PCT in patients with severe COVID-19. We excluded articles not regarding COVID-19 or not reporting PCT level, studies not in severe patients, review articles, editorials or letters, expert opinions, comments, and animal studies. Nine studies were included in the analysis. The odds of having more severe COVID-19 disease was higher in subjects with elevated PCT (≥0.05ng/mL) compared with those having low procalcitonin (<0.05ng/mL) [n=6, OR(95% CI)=2.91(1.14, 7.42), p=0.025). After estimating the mean and standard deviation values from the sample size, median, and interquartile range, a pooled effect analysis indicated higher serum PCT concentrations in patients with severe versus less severe disease [n=6, SMD(95% CI)=0.64(0.02, 1.26), p=0.042]. The results of this study showed that PCT is increased in patients with severe COVID-19 infection.

The value of serum procalcitonin in the anti-infection therapy of acute stroke patients.

Objectives:To investigate the value of dynamic monitoring of serum procalcitonin (PCT) in anti-infective therapy of patients with acute stroke.Methods:This is a case control retrospective study of acute stroke patients conducted from July 2016 to October 2018, in the Department of Neurology, Affiliated Hospital of Hebei University, who who reached within twenty four hours. They, were selected as the study subjects who were divided into infection group and non-infection group according to the inclusion and exclusion criteria. The serum PCT and CRP levels were compared between the two groups at 24 hours, 48 hours and 72 hours. In order to judge the changes of PCT level and the infection of stroke patients, different kinds of antibiotics were used for corresponding treatment. Retrospective analysis of the cases that did not monitor PCT anti infective treatment before July 2016 were compared with the cases that monitored PCT to guide anti infective treatment after July 2016, and compared the efficacy of antibiotics.Results:The serum PCT level of patients in the infection group was significantly higher than that of patients in the noninfection group (P<0.001). For the patients whose PCT<0.5 ng/ml within 72 hour, anti-infective therapy was not administered. However, for those patients whose PCT<0.5 ng/ml and CRP rose significantly, WBC, body temperature and chest CT were closely monitored. For the patients whose PCT increased slightly (0.5 ng/ml<PCT<2.0 ng/ml), first-generation and second-generation cephalosporin or semisynthetic penicillin, such as mezlocillin, were administered. For the patients whose PCT increased moderately (5 ng/ml>PCT>2 ng/ml), mezlocillin/ sulbactam or ceftriaxone/ tazobactam was administered. For patients whose PCT increased significantly (PCT>5 ng/ml), carbapenem antibiotic or a combination of two antibiotics was administered.Conclusion:Dynamic detection of serum PCT concentration can make accurate judgment on the severity of bacterial infection in patients with acute stroke and guide the rational application of antibiotics.

Serum Procalcitonic (PCT) Versus Serum C - Reactive Protein (CRP) for Severity of Organ Dysfunction in Sepsis

Background: Intensive care units (ICUs), despite advances in critical care nursing, have frequent issues with early diagnosis and adequate treatment. Recently discovered world-class procalcitonin (PCT), a revolutionary laboratory marker, has been shown to be useful in this regard. The objective is to Comparison of concentrations of serum procalcitonin (PCT) and c-reactive protein (CRP) with a comparable level of organ malfunction during sepsis and evaluation of the interaction between serum PCT and CRP concentrations with different organ malfunction occurrence in sepsis. Design: It is a Hospital-Based Prospective study. Participants and Setting: Fifty people were admitted to the intensive care unit of Gandhi Medical College. Subjects and Methods: The extent of sepsis-related organ impairment was evaluated with the sequential organ failure assessment (SOFA) on day 1. Patients were identified by category 1(0-6), category 2(7-12), group 3(13-18), and group 4(19-24) in 4 separate classes with varying organ impairment seriousness of sepsis. Serum PCT and CRP concentrations have been measured. Results: The majority of the patients belonged to the age groups of 60-69 years (30%) and 50-59 years (22%) Majority of the patients belonged to the Sofa group 1 around 42% followed by sofa group 2 with 38%, sofa group 3 with 16% and the least belonged to the sofa group 4 with 4%. The mean PCT and CRP concentration in those who survived was 14.73 ng/ml and 149.916mg/L respectively and in those who died were 45.76 ng/ml (p-value &lt;0.001) and 183.584 mg/L (p-value 0.172) respectively. The linear correlation between PCT plasma concentrations and the four groups was significantly stronger than with CRP. Conclusion: In SOFA and serum PCT, The level of organ dysfunction and complications in sepsis patients is closely related to serum CRP levels.

Elevated serum procalcitonin early after extensive burn: influencing factors and clinical significance

The study was carried out to analyze the factors influencing the elevated serum procalcitonin (PCT) levels during the early phase of extensive burn, and to investigate its potential for sepsis prediction and prognosis. Clinical data of 324 patients with extensive burns treated at our department from July 2014 to December 2019 were retrospectively analyzed. Approximately half of the patients (50.93%) exhibited elevated serum PCT concentrations during the early phase, and elevated PCT levels may not be caused by infections. Early-phase PCT level was an independent risk factor for sepsis occurrence in extensive-burn patients within 60 days of injury. Burn index, degree of inhalation injury, and APACHE-II score influenced PCT level elevation during the early phase. Patient age, burn index, APACHE-II score at admission, early-phase PCT level, and sepsis occurrence were risk factors for mortality in extensive-burn patients. During the early phase, approximately 50.93% of the extensive-burn patients exhibited elevated PCT levels, which were associated with non-infectious factors. As elevated PCT level during the early phase predicted sepsis occurrence within 60 days of injury and was significantly associated with patient mortality, it might be a potential burn severity indicator during the early phase of burn injury.

Background-Free Chromatographic Detection of Sepsis Biomarker in Clinical Human Serum through Near-Infrared to Near-Infrared Upconversion Immunolabeling.

Luminescence nanomaterial-based lateral flow assay (LFA) is promising for point-of-care tests. However, the detection sensitivity and accuracy are often affected by the interferences of autofluorescence and photon scattering from nitrocellulose membrane and colored plasma. Here, we describe a near-infrared to near-infrared upconversion nanoparticle (UCNP) immunolabeled LFA for background-free chromatographic detection of sepsis biomarker procalcitonin (PCT) in clinical human plasma. This upconversion immunolabeling enables both light excitation (at ∼980 nm) and anti-Stokes emission (at 800 nm) to be adopted within the first biological window (700-1000 nm), which eliminates background autofluorescence as well as photon scattering interferences, empowering a high-sensitivity detection without complicated procedures. After optimization, the described assay presented a limit of detection reaching down to 0.03 ng/mL, lower than the normal level (0.05 ng/mL), while having a detection range of 0.03-50 ng/mL that covers the clinical PCT level of interest (0.5-10 ng/mL). The assay recoveries in human serum samples were evaluated to be about 95-110%, whereas the inter- and intra-assay coefficient variations were both determined to be below 15%. Importantly, measured PCT concentrations in clinical samples are in good correlation with that of the electrochemiluminescence immunoassay (Roche) widely applied in large clinical settings. This near-infrared to near-infrared upconversion immunolabeling approach has direct implications for ultrasensitive and background-free point-of-care detection of other serum biomarkers in resource-limited clinical settings.

A therapeutic biomarker endocan in infective endocarditis

Background: In infectious endocarditis, previous biomarkers such as C-related protein (CRP) and procalcitonin (PCT) have been difficult to determine the appropriate timing of antibiotic treatment termination. Endocan is a novel biomarker of sepsis or bacteremia. In this study, we investigated effectiveness of endocan as a therapeutic biomarker in infective endocarditis. Methods and materials: This prospective study was conducted between September 2015 and November 2018. Subjects comprised patients aged ≥20 years admitted due to infective encocarditis. Infective endocarditis was diagnosed accodting to the modified Duke Criteria. Biomarkers were measured during the four following periods: day 0, on the admission day; day 35, between 3 and 5 days after onset of infection; and day 79, between 7 and 9 days after onset of infection; day 14–16, between 14 and 16 days after onset of infection; and day 2123, between 21 and 23 days after onset of infection; and day 2830, between 21 and 23 days after onset of infection. To measure serum endocan and PCT concentrations were measured by enzyme-linked immunosorbent assays, and CRP concentrations were measured by latex agglutination assays. Results: Nine patients were enrolled in this study. At the onset of infection, serum endocan was elevated (mean 2.21 ng/mL), and decreased during the course of treatment (mean 0.66 ng/mL). The decrease rate of serum endocan during the treatment was smaller than those of PCT and CRP. When the cut-off of endocan is 0.7 ng/mL, the rate of cases with endocan level lower than the cutoff was 0% on day 0, 20% on day 21, and 85.7% on day 28. The rate of cases with CRP lower than the normal level was 44.4% on day 28, and the rate of cases with PCT lower level than the cutoff was 60% on day 21. Conclusion: During the treatment of infective endocarditis, serum endocan gradually decreased. By setting the cutoff of endocan, serum endocan could be a useful biomarker for determing the timing of treatment termination in infective endocarditis.

Analysis of Risk Factors and Clinical Indicators in Bloodstream Infections Among Patients with Hematological Malignancy.

PurposeThe incidence of bloodstream infection (BSI) is more common in patients with hematological malignancy. It is important to distinguish infectious episodes from noninfectious episodes. The present study was aimed to describe the epidemiology, clinical indexes, and antibiotic use for in-hospital bloodstream infections of hematological malignancy patients.Patients and MethodsSingle-center retrospective research was performed on hematological malignancy patients admitted to our hospital from July 2015 to March 2018. Laboratory and clinical information from 322 febrile patients were acquired. These episodes were divided by blood culture results into two groups: 1) blood culture positive-group, 2) blood culture negative-group.ResultsIn the 322 febrile cases, 81 (25.2%) patients were blood culture positive, and among them, Gram-negative (G-) bacteria (51.9%) were more isolated than Gram-positive (G+) bacteria (32.1%) and fungi (7.4%). Gram-negative bacteria were more likely to have drug resistance than G+ bacteria. Independent risk factors revealed that patients with complications, high levels of procalcitonin (PCT), glucose, interleukin-6 (IL-6), and d-dimer (D-D), and low concentration of albumin were correlated with the occurrence of BSI. PCT, IL-6 and D-D performed well in differentiating the positive group from the negative group. Moreover, IL-6 and D-D showed excellent performance in differentiating G- and G+ groups, with the areas under the curve all above 0.8.ConclusionWe analyzed the risk factors for BSI in patients with hematological malignancy, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians insight into the diagnosis and treatment of BSI.

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease.

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before–after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14–18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.

PREDICTING INFECTIOUS COMPLICATIONS IN ACUTE PANCREATITIS COMPLICATED BY ASCITIS AND PERITONITIS

Ascites and peritonitis are fairly common complications of acute pancreatitis in the early stage of the disease. At the beginning of acute severe pancreatitis, in most cases, death occurs as a result of multiple organ failure, and starting from the second week, infectious complications can play a more serious and adverse role. However, the diagnosis of infected pancreatitis is difficult as the clinical picture does not differ from the inflammatory reaction caused by pancreatitis itself. Although the peak of infectious complications is observed mainly from the second to the fourth week since the onset of the disease, the timing of infection in pancreatic necrosis is variable and unpredictable. The aim of the study was to analyze the prognostic potential of procalcitonin in predicting the development of infectious complications in the dynamic course of acute pancreatitis complicated by ascites and peritonitis. We analyzed the findings obtained from a comprehensive examination and treatment of 18 patients with acute pancreatitis complicated by enzymatic ascites and peritonitis, including 13 patients who were treated at the surgical department of M. Sklifosovskiy Poltava Regional Clinical Hospital, and 5 patients at other emergency care settings in Poltava for 2017 – 2019. In addition to standards examination methods, procalcitonin was assessed as a biomarker to predict the adverse course of the disease in the early period. Statistical analysis of the findings was performed by the program "STATISTICA 10.0" (StatSoft, Inc., USA); methods of descriptive statistics to calculate qualitative indicators as frequencies and their percentages in the study groups were applied. The statistical significance of differences was determined by a nonparametric method between the indicators of independent groups using Fisher's exact test. Differences at p &lt;0.05 were considered statistically significant. Infectious complications in the dynamics of the disease occurred in 39% of patients in the study group. 86% of them demonstrated an increased procalcitonin concentration at admission to the hospital. A significant difference was found (p = 0.005) when comparing differences in the occurrence of infectious complications in the dynamics of the disease in the patients of the study group depending on the presence of elevated concentrations of procalcitonin or its absence at the time of hospital admission. We can suggest that measuring procalcitonin to predict the occurrence of infectious complications in the dynamics of the disease will allow us to detect patients in who reduced risk of flora translocation by parenteral drugs being tropic to pancreatic tissue and early oral antibiotic prophylaxis may lessen the incidence of septic complications.

Soluble P-selectin, procalcitonin, transforming growth factor (TGF)-β and apo-proteins in association with the components of metabolic syndrome in obese individuals.

Metabolic syndrome (MetS) is a clinical disorder with widespread prevalence. In the current study, we aimed to investigate the association between serum soluble P-selectin, procalcitonin, transforming growth factor (TGF)-β and apo-proteins with the components of metabolic syndrome in obese individuals. Sixty two obese patients with MetS and sixty five obese apparently healthy controls were participated in the current case-control study. The participants' anthropometric assessments and systolic and diastolic blood pressure (SBP and DBP) were measured. Serum lipids and the concentrations of ox-LDL, P-selectin, procalcitonin, TGF-β and apo-proteins were measured with commercial ELIZA kits. Serum TG and TC were significantly higher in obese subjects with MetS; while TGF-β, procalcitonin, apoprotein B and insulin concentrations were higher in obese non- MetS group. In obese subjects with MetS, procalcitonin was in positive association with ox-LDL and apoprotein-B was in positive association with HDL. In obese subjects without MetS, apoprotein -B was in positive association with WC and HDL and WC. The current study found several associations between serum lipids and PCT and serum apo-proteins in obese individuals either with or without MetS. Further studies with large sample size are warranted to better elucidate the observed relationships and underlying mechanism. Not Applicable.

Factors Associated with Survival and Severe Cytokine Release Syndrome of Patients with Relapsed/Refractory B-ALL Receiving CD19 CAR-T Cell Therapy

Background : Chimeric antigen receptor-modified T (CAR-T) cells against CD19 have achieved great therapeutic effect in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, factors associated with the duration of survival and the occurrence of severe cytokine release syndrome (CRS) after CD19 CAR-T cell therapy have not been fully defined. Patients and Methods: We analyzed 24 patients with relapsed/refractory B-ALL who received CD19 CAR-T cell therapy in a phase Ⅰ/Ⅱ clinical trial (ClinicalTrials.gov, NCT02349698). Infused CAR-T cell characteristics, its expansion kinetics in vivo, patient characteristics and laboratory parameters were analyzed for their correlation with overall survival (OS), progression-free survival (PFS), and the incidence of severe CRS. Results: Sixteen patients achieved complete remission (CR), among which 13 achieved minimal residual disease-negative CR. Patients achieved CR had significantly prolonged OS and PFS compared with those who did not. Multivariable cox regression showed that lower peak of CAR-T cell expansion and the occurrence of severe CRS were significantly associated with both inferior OS and inferior PFS, and higher proportion of effector memory T cells in the infused cells was only significantly associated with inferior PFS. Nineteen patients developed CRS, among which 6 developed severe CRS. Compared patients with mild CRS, patients with severe CRS experienced worse vital sign instability and pancytopenia, higher incidences of coagulation and organ dysfunctions, and higher concentrations of procalcitonin and cytokines. Multivariable logistic regression showed that higher pretreatment disease burden was independent predictor of severe CRS. Conclusions: Clinical and biological factors correlated with survival and severe CRS of refractory/relapsed B-ALL patients receiving CD19 CAR-T cell therapy were identified. These data may be helpful for improving the efficacy of CAR-T cell therapy, facilitating the recognition and early intervention of severe CRS. Disclosures No relevant conflicts of interest to declare.

Influence of myocardial damage on serum procalcitonin in ST-elevation myocardial infarction

Abstract Background Myocardial tissue injury due to acute ST-elevation myocardial infarction (STEMI) initiates an inflammatory response with a release of systemic inflammatory biomarkers including C-reactive protein (CRP) and white blood cell count (WBCc), which, however, hampers the usefulness of these routine biomarkers to identify concomitant infections. The clinical role of Procalcitonin (PCT), a promising marker of bacterial infections, to detect concomitant infections in acute STEMI is unknown, mainly because it is unclear whether myocardial injury per se induces a systemic PCT release. Purpose To investigate release kinetics of serum PCT in the acute setting of STEMI and possible associations with myocardial injury markers as comprehensively assessed by cardiac magnetic resonance (CMR) imaging. Methods In this prospective observational study, we included 141 STEMI patients treated with primary percutaneous coronary intervention (PCI). Concentrations of PCT, high-sensitivity CRP (hs-CRP), WBCc and high-sensitivity cardiac troponin T (hs-cTnT) were measured serially at day 1 and day 2 after infarction. CMR imaging to assess infarct size (IS), extent of microvascular injury (MVI) and occurrence of intramyocardial haemorrhage (IMH) was performed within the first week following STEMI. Results Median concentrations of PCT were 0.07μg/l at both time points. In 140 patients (99%), both PCT values were within the normal range (≤0.5μg/l). Whereas hs-CRP, WBCc, and hs-TnT were significantly correlated with CMR markers of myocardial damage, PCT did not show significant correlations (all p&amp;gt;0.10) with IS (PCT24h: r=0.07; PCT48h: r=0.13) or MVI (PCT24h: r=−0.03; PCT48h: r=0.09). Furthermore, PCT failed to discriminate between large and small IS or MVI or between presence and absence of IMH (AUC values:0.46–0.55). Conclusions In the acute phase after PCI for STEMI, circulating PCT remained unaffected by the extent of myocardial and microvascular tissue damage as visualized by CMR imaging. These data highlight the clinical potential of PCT to identify concomitant infections and to guide antibiotic treatments in STEMI patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund, Tiroler Wissenschaftsförderung

Copeptin, albumin and routine inflammatory markers are predictors of one-year mortality in patients with advanced heart failure underwent cardiac transplantation evaluation

Abstract Introduction Despite significant advances in the prevention and treatment of heart failure (HF), the prognosis for patients with advanced stage of the disease is still poor. Therefore, a better understanding of the underlying HF pathophysiological mechanisms is crucial to improve prognosis in patients with advanced HF. One important research area is the role of inflammation in the pathophysiology of HF. Purpose This study aimed to investigate factors associated with mortality in HF patients with particular emphasis placed on inflammatory markers. Methods This is a prospective analysis of 282 optimally treated HF patients hospitalised in Cardiology Department between 2016 and 2018 for heart transplantation (HT) evaluation. Patients with contraindications to HT were excluded from the study. At the baseline echocardiography, routine laboratory tests, an ergospirometric exercise test, and right heart catheterisation were performed in all patients. In addition, 10 ml of peripheral blood was collected to determine inflammatory biomarkers. Human procalcitonin and copeptin concentrations were measured by the sandwich enzyme-linked immunosorbent assay (ELISA) with the commercially available kit. A highly sensitive latex-based immunoassay was used to detect plasma C-reactive protein (CRP) using the COBAS Integra 70 analyzer. The end-point of the study was all-cause mortality during one-year follow-up. The study protocol was approved by the Local Ethics Committee of our medical university. All patients provided informed, voluntary consent to participate in the study. Results The median age of patients was 57 (51–60) and 87.6% of them were male. A total of 79 (28%) patients died during a one-year follow-up. Multivariate analysis of the Cox proportional hazard model confirmed that procalcitonin [hazard ratio (HR) 1.003 (1.002–1.003), p&amp;lt;0.001], high sensitivity C-reactive protein (CRP) [HR 1.109 (1.039–1.183), p&amp;lt;0.002], copeptin [HR 1.109 (1.019–1.207), p&amp;lt;0.02] and albumin [HR 0.925 (0.873–0.979), p&amp;lt;0.01] serum concentrations, as well as Erythrocyte Sedimentation Rate (ESR) [HR 1.031 (1.001–1.063) p&amp;lt;0.05] were associated with mortality during a one-year follow-up. Conclusions Our study demonstrated that higher procalcitonin, CRP and copeptin serum concentrations as well as higher ESR and lower albumin serum concentrations are independently associated with reduced survival in patients with advanced HF. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of Silesia