Plasma Procalcitonin Levels Research Articles

Persistently high plasma procalcitonin levels despite successful treatment of tuberculous pleuritis and tuberculous lymphadenitis patients

In a prospective cohort study, we evaluated plasma PCT levels in 48 TB lymphadenitis (TBLN) and 41 TB pleuritis (TBPE) patients. Measurements of PCT were done in unstimulated plasma of microbiologically and clinically confirmed TBLN and TBPE patients registered for anti-TB treatment at a tertiary care hospital in Lahore, Pakistan. Plasma levels of PCT were found to be raised in 89% of the patients at baseline with a median of 1.5 ng/ml. Levels were higher (p = 0.001) in TBLN as compared to TBPE (2.69, 0.96 ng/ml). PCT levels were not related to the bacterial burden depicted by culture positivity in these patients. PCT showed a negative correlation with the severity of constitutional symptoms (rho = − 0.238, p = 0.034), and inflammatory biomarkers; ferritin (rho = − 0.43, p < 0.001), INF-γ (rho = − 0.314, p = 0.003), TNF-α (rho = − 0.220, p = 0.039), IL-6 (rho = − 0.224, p = 0.035), and several chemokines of CCL and CCXL group. Raised plasma levels of PCT did not decrease with anti-TB treatment, indicating it is not a good biomarker to monitor treatment response in TBLN and TBPE patients. More studies with a larger number of confirmed EPTB cases are needed to define the role of PCT and its interaction with other biomarkers in EPTB.

Early diagnostic value of Presepsin in sepsis: a prospective study on a population with suspected sepsis in fever clinics

To analyze the early diagnostic value of plasma soluble cluster of differentiation 14 subtype (sCD14-ST, Presepsin) in sepsis in a population with suspected sepsis in fever clinic. A prospective observational study was conducted. The patients admitted to the fever clinic of Beijing Chaoyang Hospital from April to December 2022 were enrolled as the study objects. According to sequential organ failure assessment (SOFA) score, the patients were divided into low SOFA score group (SOFA score ≤3) and high SOFA score group (SOFA score > 3). Venous blood was collected at the time of admission. The level of plasma Presepsin was detected by chemiluminescence enzyme-linked immunoassay. The level of plasma procalcitonin (PCT) was detected by enzyme-linked immunofluorescence method. The level of C-reactive protein (CRP) was detected by scattering turbidimetry. White blood cell count (WBC) and neutrophil count (NEUT) were measured by automatic blood cell analyzer. For patients with fear of cold or chills, venous blood of upper limbs was taken for blood culture at the time of admission. The differences in inflammatory biomarkers were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen the early risk factors of sepsis in fever outpatients with suspected sepsis. Receiver operator characteristic curve (ROC curve) was drawn to investigate the early diagnostic value of Presepsin and other inflammatory markers in sepsis, and to analyze the optimal cut-off value. A total of 149 fever outpatients with suspected sepsis were enrolled, including 92 patients with low SOFA score and 57 patients with high SOFA score. Plasma PCT and Presepsin levels in the high SOFA score group were significantly higher than those in the low SOFA score group [PCT (μg/L): 0.77 (0.18, 2.02) vs. 0.22 (0.09, 0.71), Presepsin (ng/L): 1 129.00 (785.50, 1 766.50) vs. 563.00 (460.50, 772.25), both P < 0.01]. There was no significant difference in WBC, NEUT, CRP or positive rate of blood culture between the high and low SOFA score groups [WBC (×109/L): 11.32±5.47 vs. 11.14±5.29, NEUT (×109/L): 9.88±4.89 vs. 9.60±5.10, CRP (mg/L): 54.05 (15.95, 128.90) vs. 46.11 (19.60, 104.60), blood culture positivity rate: 42.3% (11/26) vs. 29.4% (10/34), all P > 0.05]. Multivariate Logistic regression analysis showed that Presepsin was an early risk factor for sepsis in suspected sepsis patients in fever clinics [odds ratio (OR) = 16.96, 95% confidence interval (95%CI) was 6.35-45.29, P = 0.000]. ROC curve analysis showed that the early diagnostic value of Presepsin in sepsis was significantly better than WBC, NEUT, CRP, PCT, and blood culture [the area under the ROC curve (AUC) and 95%CI: 0.832 (0.771-0.899) vs. 0.522 (0.424-0.619), 0.532 (0.435-0.629), 0.533 (0.435-0.632), 0.664 (0.574-0.753), 0.554 (0.458-0.650)]. When the optimal cut-off value of Presepsin was 646.50 ng/L, its sensitivity and positive predictive value were higher than those of WBC, NEUT, CRP, and PCT (sensitivity: 89.5% vs. 38.6%, 68.4%, 38.6%, 57.9%; positive predictive value: 64.6% vs. 44.9%, 44.3%, 47.8%, 55.9%). Plasma PCT and Presepsin have early diagnostic value for sepsis in suspected sepsis patients in fever clinics, and Presepsin is more sensitive than PCT and can be used as an early marker of sepsis.

A biomarker panel of C-reactive protein, procalcitonin and serum amyloid A is a predictor of sepsis in severe trauma patients

Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Показатели нового полуколичественного экспресс-теста на прокальцитонин у пациентов с внебольничной пневмонией при наличии и отсутствии артериальной гипертензии

The presence of cardiovascular diseases can be an independent risk factor for an unfavorable prognosis of community-acquired pneumonia (CAP) and cause its erased course, which significantly complicates the timely diagnosis. It has been reported that assessment of plasma procalcitonin (PCT) levels may be useful in the differential diagnosis of lung diseases. Aim. To study the levels of a new semi-quantitative rapid PCT test (PCT RT) of plasma in therapeutic patients with CAP depending on the presence or absence of arterial hypertension (AH). Design. The simultaneous comparative study. Materials and methods. The study included 123 patients hospitalized with a diagnosis of CAP: 41 patients (mean age 69.8 ± 11.9 years) with hypertension and 82 patients (mean age 39.3 ± 16.7 years) without hypertension, who made up the comparison group. Using a new semi-quantitative RT and the method of enzyme-linked immunosorbent assay, the plasma PCT level was determined before the start of antibiotic therapy. Results. In patients with CAP and hypertension, positive PCT RT results were registered 1.8 times more often than in the comparison group — 19 (46.3%) people and 21 (25.6 %) people, respectively (p = 0.018), borderline values of PCT RT — 2.2 times more often: in 13 (31.7%) people and 12 (14.6%) people (p = 0.001) patients, respectively. The comparison group was characterized by negative PCT RT values, which were recorded in 61 (74.4%) of cases (p = 0.001). Quantitative PCT scores did not have statistically significant differences in the groups studied. In the group of patients with CAP and hypertension, positive correlations of PCT RT with body temperature (r = 0.329; p = 0.038), quantitative PCT (r = 0.505; p = 0.001), plasma glucose levels (r = 0.325; p = 0.041) and potassium (0.325; p = 0.041) were established. Conclusion. Patients with CAP and hypertension in comparison with those without hypertension are characterized by positive values of the new PCT RT, which have positive correlations with body temperature, quantitative PCT values, and plasma glucose and potassium levels. Keywords: community-acquired pneumonia, arterial hypertension, diagnostics, procalcitonin, procalcitonin rapid test.

Immunological and biochemical biomarker alterations among SARS-COV-2 patients with varying disease phenotypes in Uganda

Every novel infection requires an assessment of the host response coupled with identification of unique biomarkers for predicting disease pathogenesis, treatment targets and diagnostic utility. Studies have exposed dysregulated inflammatory response induced by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as significant predictor or cause of disease severity/prognosis and death. This study evaluated inflammatory biomarkers induced by SARS-CoV-2 in plasma of patients with varying disease phenotypes and healthy controls with prognostic or therapeutic potential. We stratified SARS-CoV-2 plasma samples based on disease status (asymptomatic, mild, severe, and healthy controls), as diagnosed by RT-PCR SARS-CoV-2. We used a solid phase sandwich and competitive Enzyme-Linked Immunosorbent Assay (ELISA) to measure levels of panels of immunological (IFN-γ, TNF-α, IL-6, and IL-10) and biochemical markers (Ferritin, Procalcitonin, C-Reactive Protein, Angiotensin II, Homocysteine, and D-dimer). Biomarker levels were compared across SARS-CoV-2 disease stratification. Plasma IFN-γ, TNF-α, IL-6, and IL-10 levels were significantly (P < 0.05) elevated in the severe SARS-CoV-2 patients as compared to mild, asymptomatic, and healthy controls. Ferritin, Homocysteine, and D-dimer plasma levels were significantly elevated in severe cases over asymptomatic and healthy controls. Plasma C-reactive protein and Angiotensin II levels were significantly (P < 0.05) higher in mild than severe cases and healthy controls. Plasma Procalcitonin levels were significantly higher in asymptomatic than in mild, severe cases and healthy controls. Our study demonstrates the role of host inflammatory biomarkers in modulating the pathogenesis of COVID-19. The study proposes a number of potential biomarkers that could be explored as SARS-CoV-2 treatment targets and possible prognostic predictors for a severe outcome. The comprehensive analysis of prognostic biomarkers may contribute to the evidence-based management of COVID-19 patients.

Case-Control Study: Endogenous Procalcitonin and Protein Carbonylated Content as a Potential Biomarker of Subclinical Mastitis in Dairy Cows.

Procalcitonin (PCT) and protein carbonylated content (PCC) are promising biomarkers for bacterial infection and inflammation in veterinary medicine. This study examined plasma PCT and PCC levels in healthy cows (H) and cows with subclinical mastitis (SCM). A total of 130 cows (65 H and 65 SCM) were included in this study. Blood samples were collected, and plasma was frozen at -80 °C. PCT levels were determined using a bovine procalcitonin ELISA kit, while PCC was measured following the methodology of Levine et al. Statistical analysis revealed a significant difference in PCT levels between H (75.4 pg/mL) and SCM (107.3 pg/mL) cows (p < 0.001) and significantly lower concentrations of PCC in the SCM group (H: 0.102 nmol/mL/mg, SCM: 0.046 nmol/mL/mg; p < 0.001). The PCT cut-off value for distinguishing healthy and subclinical mastitis animals was >89.8 pg/mL (AUC 0.695), with a sensitivity of 66.2% and specificity of 69.2%. PCT showed potential value as a diagnostic tool to help in decision making for subclinical mastitis cases, while PCC requires further studies to investigate the trend of this biomarker during localized pathology.

Linear and non‑linear indices of vagal nerve in relation to sex and inflammation in patients with Covid‑19.

Hyperinflammation is one of the most important pathophysiological risk factors for poor prognosis in patients with coronavirus disease-2019 (Covid-19). Low vagal neuro-immune modulation can lead into this kind of immune dysregulation. The association between vagal activity, sex and inflammatory markers were investigated in patients with Covid-19. A total of 19 patients with Covid-19 were included in the present study. Vagus nerve activity was indexed by heart rate variability (HRV) derived from electrocardiogram at hospital admission. Linear HRV parameters included the root mean square of successive RR interval differences (RMSSD) and high-frequency HRV (HF-HRV), while non-linear parameters included 2 UV%. Immune/inflammatory parameters included C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil/lymphocyte ratio (NLR), systemic inflammatory index (SII), and procalcitonin (PCT). It has been revealed that both linear HRV indices HF-HRV and RMSSD, are significantly negatively correlated with CRP and IL-6, independent of age. The non-linear index of 2 UV% is significantly negatively correlated with NLR and SII, which reflect subtle changes in the response of immunocompetent cells. Patients that received high-flow nasal oxygen therapy had significantly higher IL-6 and CRP levels and lower levels of HF-HRV and RMSSD. These patients also had a significantly longer length of stay in hospital (LOS) than patients receiving low-flow oxygen therapy. Men had higher plasma PCT levels and longer LOS in hospital than women, and PCT statistically explained (mediated) the association between sex and LOS. The present study showed different correlations of linear and non-linear vagal indexes of HRV and inflammatory markers in patients with Covid-19. Significant sex differences in certain inflammatory markers were also observed, which may very well verify previous findings of poor prognosis in men with Covid-19. HRV reflects a continuous interaction between the sympathetic and parasympathetic autonomic nervous systems, which are affected by mental or physical stress, and certain disease states. The increased sympathetic and decreased parasympathetic vagal tone contribute to a higher risk of diseases associated with inflammation, cardiovascular disease, cancer, pulmonary diseases and other pathologies, including infectious diseases such as Covid-19. The present study showed that higher RMSSD (a marker of vagal activity) in Covid-19 patients is associated with lower levels of inflammatory biomarkers, a lower need for treatment and is negatively correlated with intensive care unit admission, leading to a shorter hospital stay. These findings support the idea that activation of vagus nerve may help certain Covid-19 patients by reducing the cytokine storm and excessive inflammation.

A novel HCP (heparin-binding protein-C reactive protein-procalcitonin) inflammatory composite model can predict severe acute pancreatitis

Severe acute pancreatitis (SAP) presents with an aggressive clinical presentation and high lethality rate. Early prediction of the severity of acute pancreatitis will help physicians to further precise treatment and improve intervention. This study aims to construct a composite model that can predict SAP using inflammatory markers. 212 patients with acute pancreatitis enrolled from January 2018 to June 2020 were included in this study, basic parameters at admission and 24 h after hospitalization, and laboratory results such as inflammatory markers were collected. Pearson's test was used to analyze the correlation between heparin-binding protein (HBP), procalcitonin (PCT), and C-reactive protein (CRP). Risk factors affecting SAP were analyzed using multivariate logistic regression, inflammatory marker models were constructed, and subject operating curves were used to verify the discrimination of individual as well as inflammatory marker models and to find the optimal cut-off value based on the maximum Youden index. In the SAP group, the plasma levels of HBP, CRP, and PCT were 139.1 ± 74.8 ng/mL, 190.7 ± 106.3 mg/L and 46.3 ± 22.3 ng/mL, and 25.3 ± 16.0 ng/mL, 145.4 ± 67.9 mg/L and 27.9 ± 22.4 ng/mL in non-SAP patients, with a statistically significant difference between the two groups (P < 0.001), The Pearson correlation analysis showed a positive correlation between the three values of HBP, CRP, and PCT. The results of the multivariate logistic regression analysis showed that HBP (OR = 1.070 [1.044–1.098], P < 0.001), CRP (OR = 1.010 [1.004–1.016], P = 0.001), and PCT (OR = 1.030[1.007–1.053], P < 0.001) were risk factors for SAP, and the area under the curve of the HBP-CRP-PCT model was 0.963 (0.936–0.990). The HCP model, consisting of HBP, CRP, and PCT; is well differentiated and easy to use and can predict the risk of SAP in advance.

Associations between indicators of new semi-quantitative express-test for procalcitonin and indicators of saturation in patients with community-acquired pneumonia

Objective. To evaluate the associations between the indicators of a new semi-quantitative express-test for procalcitonin and saturation levels in hospitalized patients with community-acquired pneumonia.&#x0D; Due to a high rate of growth of the incidence of severe community-acquired pneumonia, which leads to disability of the working population and claims thousands of lives, there is a need for early verification of the severity degree and a timely initiation of treatment. Traditional clinical, radiologic, laboratory and bacteriological criteria for inflammatory reactions (fever, increased pulmonary infiltration and leukocytosis, detection of potential pathogens in sputum or hemocultures) are not specific for pneumonia. Similar clinical and radiologic manifestations can also be noted in other pathological conditions, for example, in atelectasis of the lung, lung infarction, congestive heart failure, as well as acute respiratory distress syndrome. In this regard, the study of new diagnostic markers of community-acquired pneumonia is an actual direction in modern therapeutic diagnostics. Being a fast and highly sensitive method, the express test for procalcitonin can be a valuable predictive marker for the severe course of community-acquired pneumonia. Of interest is the relationship of procalcitonin with an indicator reflecting the presence of respiratory failure the level of saturation.&#x0D; Materials and methods. A single-stage comparative study involved 123 patients admitted to the hospital with a confirmed diagnosis of community-acquired pneumonia. On the first day after admission to the hospital, all patients underwent a general clinical examination, an overview X-ray of the chest organs, and determination of the plasma procalcitonin level using a semi-quantitative express-test as well as the saturation level. According to the results of the examination, the patients were divided into two groups: patients with saturation 94 % (n=43), and patients with saturation 94 % (n=80). The group of patients with saturation values 94 % consisted of 23 (53.5 %) women and 20 (46.5 %) men. The group of patients with saturation values 94 % consisted of 42 (52.5 %) women and 38 (47.5 %) men. The mean age of the patients was 56.719.1 and 45.620.7 (MSD) years, respectively, p=0.005. Statistical processing of the obtained data was carried out using the SPSS 13.0 software package.&#x0D; Results. Patients with low saturation values ( 94 %) had higher heart rate (p=0.001) and respiratory rate (p=0.001), and the levels of erythrocytes (p=0.001), hemoglobin (p=0.003) and albumin (p=0.001) were significantly lower than in patients with higher saturation levels 94 %. For patients with signs of respiratory failure and saturation indices 94 %, a more pronounced increase in the level of express-test for procalcitonin was characteristic (p=0.001). According to regression analysis, the express-test for procalcitonin 2 ng/ml by 13.8 % (CI 1.5131.3), age by 3 %, and heart rate by 11 % increase the risk of low saturation in patients with community-acquired pneumonia.&#x0D; Conclusion. Low values of blood oxygen saturation 94 % in hospitalized patients with community-acquired pneumonia are directly associated with high values of the new semi-quantitative express-test for procalcitonin (more than 2 ng/ml), that can be used for individual risk stratification.

Profile Tumor Necrosis Factor Alpha and Procalcitonin in Preeclampsia and Preeclampsia with Sepsis

BACKGROUND: Preeclampsia is hypertension in pregnancy which are characterized by high blood pressure, proteinuria that occur after 20 weeks of GA. Preeclampsia remains a massive cause of maternal morbidity and mortality that 50.000 death annually. The cause of preeclampsia is still unclear but there is a possibility caused by immunological processes in micro placenta environment during the early age of pregnancy. It is suggested that cytokines such as tumor necrosis factor (TNF-α) has an important role in the pathogenesis of preeclampsia. Preeclampsia is an extreme feature of the systemic inflammatory response during pregnancy. Systemic inflammation in preeclampsia can cause organ damage and induce sepsis. The pathophysiology is initiated by a high level of pro-inflammatory cytokine that released by peripheral blood mononuclear cell (PBMC). Beside pro-inflammatory cytokine, the marker of sepsis can be shown by procalcitonin (PCT) that produced by PBMC which is activated by TNF-α. AIM: The objective of the study is to evaluate profile maternal plasma levels of TNF-α and PCT and analyze their correlation in normotensive pregnant woman, preeclamptic and preeclampsia with sepsis. METHODS: An observational cross-sectional study. The sample were normotensive, preeclamptic, and preeclamptic with sepsis (n = 18) in Bangil Hospital, Pasuruan. The level of TNF-α and PCT was measured by ELISA. The statistical analysis with SPSS 18.0 with p &lt; 0.05. RESULTS: This study showed level of TNF-α and PCT in preeclamptic with sepsis was significantly higher than control (p &lt; 0.05) and not a significant difference in preeclampsia (p &gt; 0.05). The level of TNF-α and PCT in preeclampsia compared with control was not a significant difference (p &gt; 0.05). This study showed there was no correlation between TNF-α and PCT in patients with preeclampsia with sepsis. CONCLUSION: The plasma level of TNF-α and PCT was statistically different between the control group, preeclampsia and preeclampsia with sepsis. There was no significant difference of TNF-α and PCT plasma level in preeclampsia with sepsis than preeclampsia group. There was no significant correlation between preeclampsia in woman and preeclampsia with sepsis in maternal plasma TNF-α and PCT levels.

Severe and fatal COVID-19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes.

Endotoxemia commonly occurs in severe and fatal COVID-19, suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (T2D). We aimed to determine the association of COVID-19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and withoutT2D. Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of disease severity. Increased admission GLP-1 levels (p=0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p=0.01 and p=0.001, respectively) and at 5 to 6days of hospitalisation (p=0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r=0.33, p=0.03, and r=0.54, p=0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as a new biomarker of COVID-19 severity and fatal outcome.

Role of serum procalcitonin in the diagnosis and monitoring of treatment response in treatment-naïve subjects with chronic pulmonary aspergillosis

BackgroundInterferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA. MethodsWe extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study’s primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy. ResultsWe included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5–7.4%) and 100 (91.2–100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39–0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects. ConclusionPlasma procalcitonin has poor performance in diagnosing and following subjects with CPA.

Use of non-selective B-blockers is safe in hospitalised decompensated cirrhosis patients and exerts a potential anti-inflammatory effect: Data from the ATTIRE trial.

Nonselective B-blockers (NSBBs) are believed to have pleiotropic effects beyond reducing portal pressure. However, studies also report potential harm in patients hospitalized with cirrhosis and ascites. We therefore investigated whether NSBB use at ATTIRE trial entry (Albumin to prevent infection in chronic liver failure, 2016-19) was associated with increased renal or cardiovascular dysfunction, compared the incidence of infection and plasma markers of systemic inflammation, and examined mortality at 28-days, 3 and 6-months. In ATTIRE patients grouped by NSBB use at trial entry, we studied infection at baseline, hospital acquired infection and organ dysfunction during trial treatment period and mortality, with propensity score matching to account for differences in disease severity. There were no differences in renal or cardiovascular dysfunction between patients treated with NSBBs or not, during days 3-15 of hospitalization, despite elevated serum creatinine in NSBB patients at hospitalisation. Use of NSBBs was associated with a significant reduction in infection at hospitalization (p=0.006), lower white cell counts throughout hospital stay (p<0.001) and reduced plasma procalcitonin (p=0.009) and interlukin-8 levels (p=0.04) at baseline, but markers of bacterial translocation and systemic inflammation were the same in treatment groups. There was no reduction in hospital acquired infections in patients taking NSBBs and no beneficial impact on mortality at 28-days, 3 and 6-months. Our real-world data from a completed randomised trial show that use of NSBBs in decompensated cirrhosis patients is safe during hospitalisation. We also show a potential anti-inflammatory role for NSBBs which may be mediated by a downregulation of IL-8 induced leucocytosis, that was associated with reduced infection at baseline but not a survival benefit. Wellcome Trust and Department of Health and Social Care.

QKI degradation in macrophage by RNF6 protects mice from MRSA infection via enhancing PI3K p110β dependent autophagy

BackgroundSepsis is a fatal condition commonly caused by Methicillin-resistant Staphylococcus aureus (MRSA) with a high death rate. Macrophages can protect the host from various microbial pathogens by recognizing and eliminating them. Earlier we found that Quaking (QKI), an RNA binding protein (RBP), was involved in differentiation and polarization of macrophages. However, the role of QKI in sepsis caused by pathogenic microbes, specifically MRSA, is unclear. This study aimed to investigate the role of QKI in regulation of host–pathogen interaction in MRSA-induced sepsis and explored the underlying mechanisms.MethodsTransmission electron microscope and immunofluorescence were used to observe the autophagy level in macrophages. Real-time PCR and western blot were used to analyzed the expression of mRNA and protein respectively. The potential protein interaction was analyzed by iTRAQ mass spectrometry and Immunoprecipitation. RNA fluorescence in situ hybridization, dual-luciferase reporter assay and RNA immunoprecipitation were used to explore the mechanism of QKI regulating mRNA of PI3K-p110β.ResultsThe mRNA level of QKI was aberrantly decreased in monocytes and PBMCs of septic patients with the increasing level of plasma procalcitonin (PCT). Then the mice with myeloid specific knockout of QKI was challenged with MRSA or Cecal Ligation and Puncture (CLP). Mice in these two models displayed higher survival rates and lower bacterial loads. Mechanistically, QKI deletion promoted phagocytosis and autophagic degradation of MRSA via activating p110β (a member of Class IA phosphoinositide 3-kinases) mediated autophagic response. QKI expression in macrophages led to the sequestration of p110β in mRNA processing (P) bodies and translational repression. Upon infection, the direct interaction of RNF6, a RING-type E3 ligase, mediated QKI ubiquitination degradation and facilitated PI3K-p110β related autophagic removal of pathogen. The administration of nanoparticles with QKI specific siRNA significantly protected mice from MRSA infection.ConclusionsThis study disclosed the novel function of QKI in the P body mRNA regulation during infection. QKI degradation in macrophage by RNF6 protects mice from MRSA infection via enhancing PI3K-p110β dependent autophagy. It suggested that QKI may serve as a potential theranostic marker in MRSA-induced sepsis.Graphical

Value of peripheral blood monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis

To explore the value of monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis. A prospective case-control study was designed. 30 septic patients and 30 non-septic patients who were admitted to the intensive care unit (ICU) of the PLA Army Characteristic Medical Center from March 2021 to March 2022 were enrolled. After 1, 3, and 5 days of ICU admission, peripheral blood samples were taken from patients. Flow cytometry was used to detect the proportion of monocyte subsets and the expression level of CD64 on the surface, and the difference of expression between patients in two group was analyzed. The risk variables for sepsis were analyzed using single-factor and multi-factor Logistic regression. The diagnostic efficacy of each risk factor for sepsis was determined using the receiver operator characteristic curve (ROC curve). One day after ICU admission, the proportions of monocytes and classic monocytes in white blood cells (WBC) of septic patients were significantly lower than those of non-septic patients [proportion of monocytes to WBC: (4.13±2.03)% vs. (6.53±3.90)%, proportion of classic monocytes to WBC: 1.97 (1.43, 2.83)% vs. 3.37 (1.71, 5.98)%, both P < 0.05]. The proportion of non-classical monocytes in monocytes was significantly higher in septic patients than that in non-septic patients [(11.42±9.19)% vs. (6.57±4.23)%, P < 0.05]. The levels of CD64 expression in monocytes, classic monocytes, intermediate monocytes and non-classic monocytes were significantly higher in sepsis patients than those in non-septic patients [mean fluorescence intensity (MFI): 13.10±6.01 vs. 9.84±2.83 for monocytes, 13.58±5.98 vs. 10.03±2.84 for classic monocytes, 13.48±6.35 vs. 10.22±2.99 for intermediate monocytes, 8.21±5.52 vs. 5.79±2.67 for non-classic monocytes, all P < 0.05]. Multivariate Logistic regression research showed that CD64 in typical monocytes [odds ratio (OR) = 1.299, 95% confidence interval (95%CI) was 1.027-1.471, P = 0.025] and the proportion of non-typical monocytes in monocytes (OR = 1.348, 95%CI was 1.034-1.758, P = 0.027) were the independent risk factors for sepsis. ROC curve showed that the area under the ROC curve (AUC) of CD64 expression of classical monocytes, the fraction of non-classical monocytes in monocytes, and procalcitonin (PCT) in the diagnosis of sepsis was 0.871. A correlation analysis revealed a negative relationship between the acute physiology and chronic health status evaluation II (APACHE II) on the first, third, and fifth days following ICU admission and the expression level of CD64 in patients' classic monocytes (r values were -0.264, -0.428 and -0.368, respectively, all P < 0.05). Combining the proportion of non-classical monocytes in monocytes, the level of plasma PCT, and the CD64 expression of classic monocytes in peripheral blood has good efficacy in identifying sepsis and assessing its severity.

Longitudinal changes in inflammatory biomarkers among patients with COVID-19: A nationwide study in Iceland.

ObjectivesAll SARS‐CoV‐2‐positive persons in Iceland were prospectively monitored and those who required outpatient evaluation or were admitted to hospital underwent protocolized evaluation that included a standardized panel of biomarkers. The aim was to describe longitudinal changes in inflammatory biomarkers throughout the infection period of patients with COVID‐19 requiring different levels of care.DesignRegistry‐based study.SettingNationwide study in Iceland.PatientsAll individuals who tested positive for SARS‐CoV‐2 by real‐time polymerase chain reaction (RT‐PCR) from February 28 to December 31, 2020 in Iceland and had undergone blood tests between 5 days before and 21 days following onset of symptoms.Measurements and Main ResultsData were collected from the electronic medical record system of Landspitali–The National University Hospital of Iceland. Data analyses were descriptive and the evolution of biomarkers was visualized using locally weighted scatterplot smoothing curves stratified by the worst clinical outcome experienced by the patient: outpatient evaluation only, hospitalization, and either intensive care unit (ICU) admission or death. Of 571 included patients, 310 (54.3%) only required outpatient evaluation or treatment, 202 (35.4%) were hospitalized, and 59 (10.3%) were either admitted to the ICU or died. An early and persistent separation of the mean lymphocyte count and plasma C‐reactive protein (CRP) and ferritin levels was observed between the three outcome groups, which occurred prior to hospitalization for those who later were admitted to ICU or died. Lower lymphocyte count, and higher CRP and ferritin levels correlated with worse clinical outcomes. Patients who were either admitted to the ICU or died had sustained higher white blood cell and neutrophil counts, and elevated plasma levels of procalcitonin and D‐dimer compared with the other groups.ConclusionsLymphocyte count and plasma CRP and ferritin levels might be suitable parameters to assess disease severity early during COVID‐19 and may serve as predictors of worse outcome.

Procalcitonin levels in children affected by severe malaria compared to those with uncomplicated malaria in the absence of bacterial infection: a cross-sectional study

BackgroundProcalcitonin is an inflammatory marker strongly associated with the presence of bacterial infection. It has been considered raised in severe malaria infection as opposed to uncomplicated malaria. There are suggestions that it may be raised only when there is concomitant unnoticeable bacterial infection during a malaria crisis. We aimed to assess the difference in plasma procalcitonin levels between children affected by severe and uncomplicated malaria.MethodsWe assessed plasma procalcitonin levels in 83 children diagnosed with malaria with no clinical and biological evidence of concomitant bacterial infection. Severity of malaria was established using WHO guidelines. Procalcitonin was determined using the ELISA method. Non-parametric Mann-Whitney U test was used to compare medians across the 2 groups. Statistical significance was set for all p values < 0.05.ResultsOf the 83 participants, 28 had uncomplicated malaria, and 55 had severe malaria. PCT levels were obtained in 24 and 40 subjects of each group, respectively, and were similar in both groups; [2.76 (2.52–2.93) vs 2.74 (2.52–2.98) ng/ml, p = 0.916]. The parasite density was lower in the uncomplicated malaria group than in the severe malaria group, but not statistically significant; [22,192 (9110–44 654) vs 31 684 (13 960–73 500) parasites/μl, p = 0.178]. There was no correlation between the parasite density in the general study population and PCT levels (r = 0.072, p = 0.572).ConclusionIn the absence of overt bacterial infection, procalcitonin levels are not different between children affected with uncomplicated malaria and those with severe malaria. Therefore, bacterial infection should be thoroughly checked for in children with raised serum procalcitonin diagnosed with severe malaria.

A diagnostic test: combined detection of heparin-binding protein, procalcitonin, and C-reactive protein to improve the diagnostic accuracy of bacterial respiratory tract infections.

BackgroundRespiratory tract infection (RTI) is one of the most common diseases worldwide, and its incidence is rising year by year due to environmental pollution. Sputum culture remains the gold standard for RTI diagnosis, but its performance is limited by difficulties related to the sampling and testing of the sputum specimens. Heparin-binding protein (HBP), procalcitonin (PCT), and C-reaction protein (CRP) are Inflammatory markers. They have the advantage of being fast, accurate and reproducible, but limited by their sensitivity and specificity. We explored the clinical value of the combined detection of them in the diagnosis of bacterial RTIs.MethodsPatients who fulfilled the inclusion criteria were selected as the case group, healthy age- and sex-matched subjects were enrolled as a control group. The subjects’ HBP, PCT, and CRP levels were detected. The case group was further divided into two groups according to the bacterial culture results, and the differences in the markers were statistically analyzed. The receiver operating characteristic (ROC) curves were drawn, and the areas under the ROC curve (AUCs) were calculated to analyze the diagnostic values of each marker and their combination in parallel for bacterial RTIs.ResultsThe plasma HBP, PCT, and CRP levels of patients in the bacterial and non-bacterial infection groups were significantly higher than those of patients in the healthy control group, and were positively correlated to the severity of the disease. for HBP with an AUC of 0.785 [95% confidence interval (CI): 0.686–0.884], a sensitivity of 0.821, a specificity of 0.771; PCT with an AUC of 0.767 (95% CI: 0.664–0.870), a sensitivity of 0.773, a specificity of 0.791, and CRP with an AUC of 0.748 (95% CI: 0.642–0.854), a sensitivity of 0.839, a specificity of 0.696 in the bacterial and non-bacterial infection groups. The combined detection of HBP + CRP had the optimal diagnostic performance, with an AUC of 0.797 (95% CI: 0.698–0.895; P<0.001), a sensitivity of 0.809, a specificity of 0.800.ConclusionsThe combined detection of HBP and CRP is valuable for diagnosing bacterial RTIs and may guide the development of reasonable treatment protocols in clinical settings.

Evaluation of systemic inflammation in response to remote ischemic preconditioning in patients undergoing transcatheter aortic valve replacement (TAVR)

Systemic inflammation can occur after transcatheter aortic valve replacement (TAVR) and correlates with adverse outcome. The impact of remote ischemic preconditioning (RIPC) on TAVR associated systemic inflammation is unknown and was focus of this study. We performed a prospective controlled trial at a single center and included 66 patients treated with remote ischemic preconditioning (RIPC) prior to TAVR, who were matched to a control group by propensity score. RIPC was applied to the upper extremity using a conventional tourniquet. Definition of systemic inflammation was based on leucocyte count, C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), assessed in the first 5 days following the TAVR procedure. Mortality was determined within 6 months after TAVR. RIPC group and matched control group showed comparable baseline characteristics. Systemic inflammation occurred in 66% of all patients after TAVR. Overall, survival after 6 months was significantly reduced in patients with systemic inflammation. RIPC, in comparison to control, did not significantly alter the plasma levels of leucocyte count, CRP, PCT or IL-6 within the first 5 days after TAVR. Furthermore, inflammation associated survival after 6 months was not improved by RIPC. Of all peri-interventional variables assessed, only the amount of the applied contrast agent was connected to the occurrence of systemic inflammation. Systemic inflammation frequently occurs after TAVR and leads to increased mortality after 6 months. RIPC neither reduces the incidence of systemic inflammation nor improves inflammation associated patient survival within 6 months.

Новый полуколичественный экспресс-тест на прокальцитонин у госпитализированных пациентов с внебольничной пневмонией различной степени тяжести

Background: severe community-acquired pneumonia (CAP) makes a significant contribution to the structure of population disability and mortality, therefore, its timely diagnosis and treatment are conductive to the prevention of complications and the preservation of working capacity. A potential biomarker for the early diagnosis of severe CAP is plasma procalcitonin (PCT). Aim: to evaluate the PCT level, determined by a new semi-quantitative rapid test (RT), as a biomarker associated with the CAP severity. Patients and Methods: the study included 123 patients hospitalized with a diagnosis of community-acquired pneumonia. In the first 24 hours of hospitalization, all patients underwent general clinical examination and chest X-ray examination. The level of PCT plasma was determined using a new semi-quantitative RT and quantitative test. According to the results of the examinations, the patients were divided into 2 groups: hospitalized in the specialized pulmonology department with moderate severity of pneumonia (n=117) and hospitalized in the intensive care unit (ICU) with severe disease severity (n=6); the mean age was 49.1±21.1 and 55.7±17.5 years, respectively (p=0.460). Results: for patients with CAP hospitalized in the specialized department, negative and borderline values of PCT RT prevailed: indicators &lt;0.5 ng/mL were recorded in 70.1% of patients, levels ranged ≥0.5, but &lt;2 ng/mL — in 21.4% (p=0.001). Positive values of PCT RT prevailed in patients with in the ICU: ≥2 ng/mL, but &lt;10 ng/mL — in 16.7%, ≥10 ng/mL — in 66.7% (p=0.001). The indicators of quantitative PCT were significantly higher in patients with severe CAP — 10.80 [4.21; 61.63] ng/mL and 0.14 [0.09; 0.67] ng/mL (p=0.003). PCT RT ≥2 ng/mL with respect to severe CAP, the optimal sensitivity was 83.3%, specificity — 91.5%, the area under the ROC curve — 0.87. The diagnostic significance was assessed as very good. Conclusion: the new plasma PCT RT can be used at the first stages of the diagnosis of severe CAP in inpatients, which will optimize intra- hospital routing of patients in medical and preventive treatment facility and, respectively, determine the treatment tactics. KEYWORDS: semi-quantitative plasma procalcitonin rapid test, community-acquired pneumonia, condition severity. FOR CITATION: Bayramova S.S., Tsygankova O.V., Nikolaev K.Yu. New semi-quantitative rapid test for procalcitonin in hospitalized patients with community-acquired pneumonia of varying severity. Russian Medical Inquiry. 2022;6(7):344–351 (in Russ.). DOI: 10.32364/2587- 6821-2022-6-7-344-351.