The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.

PURPOSE: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock. MATERIALS AND METHODS: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated. RESULTS: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17). CONCLUSION: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality.

Serum calprotectin as a marker of neonatal sepsis: a hospital-based cross-sectional diagnostic study.

Background: Despite significant advances in neonatal care, neonatal sepsis remains a major contributor to mortality, morbidity, and protracted hospitalization. The development of early possible diagnostic indicators for newborn sepsis is critical. Since calprotectin participates in major biological processes, it could be a diagnostic marker for infection/inflammation. This study aimed to estimate serum calprotectin in neonates with clinical sepsis. In addition, we compared serum calprotectin with standard sepsis markers and serum procalcitonin to evaluate its diagnostic accuracy. Methods: A hospital-based cross-sectional diagnostic study of neonates identified with clinical sepsis using standard criteria was carried out. We compared estimated serum calprotectin levels to serum procalcitonin levels and conventional sepsis markers (leucocyte count, blood culture, immature to total neutrophil ratio, and C- reactive protein). We used SPSS version 25 to analyze the data. To examine diagnostic accuracy and determine a cut-off value for serum calprotectin, we used the receiver operating characteristics (ROC) curve. Results: Of the 83 subjects included, 36.5% (30/83) had blood culture positive status, the median value of serum calprotectin being 0.93 ng/ml (0.67 to 1.3). Respiratory, cardiovascular, and gastrointestinal instabilities were present in 67.5% (56/83), 59% (49/83), and 50.1% (42/83) cases, respectively. The median values of serum calprotectin, procalcitonin, TLC, and I/T ratio between neonates withpositive blood culturesand negative culturesdid not differ significantly.. On ROC, calprotectin was not predictive for blood culture positivity (sensitivity: 50%; specificity: 44% at 0.83 ng/ml of serum calprotectin) and C-reactive protein (CRP) levels (sensitivity: 57%; specificity: 67% at serum calprotectin levels of 0.89 ng/ml). However, compared with serum procalcitonin, serum calprotectin at 1.2 ng/ml had sensitivity and specificity of 60% and 73%, respectively. Conclusions: Serum calprotectin did not show a distinct advantage over the existing sepsis markers. Serum calprotectin level at 1.2 ng/ml had a sensitivity and specificity of 60% and 73%, respectively, compared to serum procalcitonin in detecting neonatal sepsis.

Relation Between Interleukin-6, Interleukin-10 And Interleukin-2 Receptor And Mortality In Severely Ill COVID-19 Patients.

Objectives: To investigate the relation involving soluble interleukin-2 receptor, interleukin-6 and interleukin-10 in hospitalised patients with severe coronavirus disease-2019 infection. Method: This single-centre cohort study was conducted at the Kafrelshiekh University Hospital, Egypt, from January to June 2022, and included all patients of either gender who were hospitalised with severe infection with the coronavirus disease-2019 isolation ward. Chemiluminescence immunoassay method was used to measure levels of procalcitonin, ferritin, soluble interleukin-2 receptor, interleukin-6 and interleukin-10. Data was analysed using SPSS version. 25. RESULTS: Of the 250 patients with median age 57.5 years (interquartile range: 45.8-66.0 years), 147(59%) were males and 103(41%) were females. Of them, 102(40.8%) patients died; 68(66.7%) males, 34(33.3%) females, median age 60.0 years (interquartile range: 48.8-70.0). Among the 148(59.2%) survivors, 79(53.4%) were males and 69(46.6%) were females, while the overall median age was 55.0 years (interquartile range: 41.5-65.8 years). The survivors had significantly lower levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 (p<0.001). Correlation analysisidentified significant positive correlation between IL-2R, IL-6 and IL-10 levels and almost all the inflammatory and coagulation parameters, including C-reactive protein, lactate dehydrogenase, procalcitonin, ferritin, D-dimer and fibrinogen (p<0.05). CONCLUSIONS: Elevated levels of soluble interleukin-2 receptor, interleukin-6 and interleukin-10 were found to be associated with greater risk of mortality in coronavirus disease-2019 patients.

Th1/Th2 cytokine levels: A potential diagnostic tool for patients with necrotizing fasciitis.

INTRODUCTION: Necrotizing fasciitis (NF) has emerged as rare but rapidly progressive, life-threatening severe skin and soft tissue infection. We conducted a study to investigate whether Th1/Th2 cytokines could serve as biomarkers to distinguish NF from class III skin and soft tissue infections (SSTIs). METHODS: A retrospective review was performed for 155 patients suffering from serious skin and soft tissue infections from October 2020 to February 2022. Th1/Th2 cytokines were obtained from peripheral blood and wound drainage fluid samples. Data on demographic characteristics, causative microbiological organisms, Th1/Th2 cytokines, c-reactive protein, procalcitonin and white blood cell (WBC) were extracted for analysis. Factors with statistical difference(p < 0.1) were included in the multivariate logistic regression model. The clinical differential diagnostic values of interleukin-2(IL-2), IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-r (IFN-r) were analyzed by receiver operating characteristic (ROC) curve. RESULTS: Among the 155 patients, 66(43%) patients were diagnosed as NF. We found no significant difference for sex, age, location of infection, coexisting condition, predisposition, duration of symptoms before admission and micro-organisms, WBC, procalcitonin and c-reactive protein in NF and class III SSTIs group. NF had higher levels of IL-6 in serum (50.46 [24.89, 108.89] vs. 11.87 [5.20, 25.32] pg/ml; p＜0.01), IL-10 in serum (3.45 [2.03, 5.12] vs. 2.51 [1.79, 3.29] pg/ml; p＜0.01), IL-2 in wound drainage fluid (0.89 [0.49, 1.33] vs. 0.63 [0.14, 1.14] pg/ml; p = 0.02), IL-6 in wound drainage fluid (5000.84 [1392.30, 13287.19] vs. 1927.82 (336.65, 6759.27) pg/ml; p＜0.01), TNF-a in wound drainage fluid (5.20 [1.49, 22.97] vs. 0.96 [0.12, 3.21] pg/ml; p＜0.01) and IFN-r in wound drainage fluid (1.32 [0.47, 4.62] vs. 0.68 [0.10, 1.88] pg/ml; p = 0.02) as compared to the class III SSTIs. Multivariate logistic regression analyses showed that IL-6 in serum, IL-10 in serum and TNF-a in wound drainage fluid exhibited independently significant associations with diagnosis of NF(p＜0.05). In ROC curve analysis of IL-2, IL-6, IL-10, TNF-a and IFN-r for diagnosis of NF, the area under the curve (AUC) of IL-6 in serum could reach to 0.80 (p＜0.001). Using 27.62 pg/ml as the cut off value, the sensitivity was 74% and the specificity was 79% in IL-6 in serum. CONCLUSIONS: Th1/Th2 cytokines, IL-6 in serum in particular, are potential biomarkers for the diagnosis of NF in the early stage. However, larger patient populations with multiple centers and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines.

Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

Toll-like receptor 4 deficiency alleviates lipopolysaccharide-induced intestinal barrier dysfunction.

BACKGROUND: The intestinal tract is considered the body's "engine" and the most impacted organ during sepsis. In this study, we explored toll-like receptor 4 (TLR4) functions in sepsis-induced intestinal barrier dysfunction. METHODS: Wild-type and TLR4-knockout (KO) mice were used to establish a sepsis-induced dysfunctional intestinal barrier model via the intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Hematoxylin and eosin staining, Transmission electron microscope, enzyme linked immunosorbent assay, western blot, quantitative real-time polymerase chain reaction, TdT-mediated dUTP nick end labeling staining, 16 S rRNA gene sequencing were used to explore differences in inflammatory cytokines, apoptosis, tight junction (TJ) protein expression, and intestinal flora diversity between groups. RESULTS: TLR4-deficiency reduced procalcitonin and C-reactive protein to prevent sepsis, and also inhibited inflammatory response by decreasing interleukin (IL)- 1ß, IL-6 and tumor necrosis factor-α levels. Also, BAX/Bcl2 and cleaved-caspase 3 expressions were decreased in TLR4-KO mice to suppress the intestinal mucosal cell apoptosis. TJ proteins, including zonula occludens protein, Occludin and Claudin-5 were significantly increased and intestinal fatty acid binding protein, myosin light chain and myosin light chain kinase were reduced in TLR4-KO mice. Additionally, 16 S rRNA gene sequencing indicated that TLR4-deficiency improved flora diversity and altered normal and abnormal bacterial proportions. CONCLUSIONS: TLR4 deficiency alleviated LPS-induced intestinal barrier dysfunction by reducing inflammatory responses and apoptosis, impairing intestinal damage, and regulating intestinal flora disturbance.

Erythrocyte and plasma selenium in children with acute inflammatory response.

OBJECTIVES: Plasma selenium may not reflect selenium status in critically ill patients because it transiently decreases inversely with the magnitude of the systemic inflammatory response. The decision to supplement selenium should ideally be based on laboratory measurements that reliably reflect selenium status. We hypothesized that erythrocyte selenium, unlike plasma selenium, is not affected by the systemic inflammatory response in critically ill children. METHODS: In a prospective study of 109 critically ill children, plasma and erythrocyte selenium concentrations were evaluated on admission, and plasma selenoprotein P was evaluated on days 1, 2, and 3 of the ICU stay. The main outcome was the effect of systemic inflammation on the erythrocyte and plasma selenium concentrations. The magnitude of the systemic inflammatory response was measured using serum C-reactive protein (CRP) and procalcitonin levels. The covariates were age, sex, anthropometric nutritional status, diagnosis of severe sepsis/septic shock, and clinical severity on admission. Multiple linear regression and generalized estimating equations were used for statistical analysis. RESULTS: Erythrocyte selenium levels were not influenced by the magnitude of the inflammatory response or by the patient's clinical severity. Procalcitonin (ß coefficient=-0.99; 95%CI: -1.64; -0.34, p = 0.003) and clinical severity (ß coefficient= -11.13; 95%CI: -21.6; -0.63), p = 0.038) on admission were associated with decreased plasma selenium concentrations. Erythrocyte selenium was associated with selenoprotein P in the first three days of ICU stay (ß coefficient=0.32; 95%CI: 0.20; 0.44, p < 0.001). CONCLUSION: Unlike plasma selenium, erythrocyte selenium does not change in children with an acute systemic inflammatory response and is associated with selenoprotein P concentrations. Erythrocyte selenium is probably a more reliable marker than plasma selenium for evaluating the selenium status in critically ill children.

[Analysis of risk factors for prolonged mechanical ventilation in patients with sepsis after abdominal surgery].

OBJECTIVE: To analyze the risk factors of prolonged mechanical ventilation (PMV) in patients with sepsis complicated by abdominal surgery, and to evaluate the predictive value of risk factors for PMV. METHODS: A retrospective case-control study was conducted. The clinical data of patients with postoperative abdominal sepsis complicated with invasive mechanical ventilation who were admitted to the intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from January 1, 2018 to December 31, 2020 were collected. The patients were divided into PMV group (duration of mechanical ventilation longer than 48 hours) and non-PMV group (duration of mechanical ventilation shorter than 48 hours) according to the duration of mechanical ventilation in ICU. The patient's gender, age, body mass index (BMI), underlying diseases, mean arterial pressure (MAP), complete blood count, blood biochemistry, arterial blood gas, cardiac function indicators, procalcitonin (PCT) at admission to the ICU, the acute physiology and chronic health evaluation II (APACHE II) and the sequential organ failure assessment (SOFA) scores in the first 24 hours of admission to the ICU, and other clinical information were recorded. Univariate and multivariate Logistic regression models were used to analyze the risk factors for PMV. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of related indicators for PMV. RESULTS: A total of 195 patients with sepsis after abdominal surgery who received invasive mechanical ventilation were enrolled, including 127 males (65.1%) and 68 females (34.9%), with the median age of 65 (21, 93) years old. There were 91 patients (46.7%) in the non-PMV group and 104 patients (53.3%) in the PMV group. Univariate analysis showed that the APACHE II score, SOFA score, cardiac troponin T (cTnT), N-terminal pro-B type natriuretic peptide (NT-proBNP) in the PMV group were significantly higher than those in the non-PMV group. Oxygenation index (PaO2/FiO2), total protein (TP) and prealbumin (PA) in the PMV group were all lower than those in the non-PMV group when admitted to ICU. In the PMV group, serum creatinine (SCr), blood urea nitrogen (BUN), cystatin C (Cys C) were significantly increased, prothrombin time (PT) was significantly prolonged, the proportion of patients with septic shock and hypertension were significantly increased as compared with those in the non-PMV group. Multivariate analysis showed that low PaO2/FiO2 at ICU admission [odds ratio (OR) = 0.995, 95% confidence interval (95%CI) was 0.992-0.999, P = 0.010], high ln PCT (OR = 1.301, 95%CI was 1.088-1.555, P = 0.004), high ln cTnT (OR = 1.562, 95%CI was 1.079-2.261, P = 0.018) and septic shock (OR = 4.967, 95%CI was 2.461-10.026, P = 0.000) were the independent risk factors for PMV in patients with sepsis after abdominal surgery. ROC curve analysis showed that the PaO2/FiO2, ln cTnT, ln PCT and septic shock had certain predictive value for PMV, the area under the ROC curve (AUC) of the four variables were 0.607, 0.638, 0.690 and 0.711, the sensitivity was 50.0%, 62.5%, 86.5% and 74.0%, and the specificity was 71.4%, 62.6%, 48.3% and 68.1%, respectively. The AUC for the joint prediction of the four variables was 0.803, with a sensitivity of 76.0% and a specificity of 78.0%. It suggested that the multivariate joint prediction of PMV was more accurate. CONCLUSIONS: Decreased PaO2/FiO2, increased PCT, increased cTnT and the occurrence of septic shock are independent risk factors for PMV in patients with sepsis complicated by abdominal surgery. The combination of above four indices was more accurate than one single variable in predicting PMV and had higher diagnostic value.

[Effect of Tetrastigma hemsleyanum on sepsis and mechanism based on network pharmacology and experimental verification].

Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1ß, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1ß, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lß, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.

Body computed tomography in sepsis: predictors of CT findings and patient outcomes in a retrospective medical ICU cohort study.

BACKGROUND: Sepsis is a life-threatening condition that requires immediate focus identification and control. However, international sepsis guidelines do not provide information on imaging choice. PURPOSE: To identify predictors of CT findings and patient outcomes in a population of septic patients from a medical ICU. MATERIAL AND METHODS: A full-text search in the radiological information system (RIS) retrieved 227 body CT examinations conducted to identify infectious sources in 2018. CT reports were categorized according to identified foci and their diagnostic certainty. Diagnostic accuracy of CT was compared to microbiological results. Clinical and laboratory information was gathered. Statistical analysis was performed using nonparametric tests and logistic regression analysis. RESULTS: CT revealed more positive infectious foci 52.4% (n = 191/227) than microbiological tests 39.3% (n = 79/201). There were no significant differences between focus-positive CT scans with regard to positive microbiological testing (p = 0.32). Sequential organ failure assessment (SOFA) scores were slightly but nonsignificantly higher in patients with a focus-positive CT, odds ratio (OR) = 0.999 (95% CI 0.997-1.001) with p = 0.52. Among C-reactive protein (CRP), procalcitonin (PCT), and leukocytes, in focus-positive versus focus-negative CT scans, CRP showed a minor but statistically significant elevation in the group with focus-positive CT scans (OR = 1.004, 95% CI = 1.000-1.007, p = 0.04). No significant association was found for PCT (OR = 1.007, 95% CI = 0.991-1.023; p = 0.40) or leukocytes (OR = 1.003, 95% CI = 0.970-1.038; p = 0.85). In 33.5% (n = 76/227) of cases, the CT findings had at least one therapeutic consequence. In 81.6% (n = 62/76), the CT findings resulted in one consequence, in 14.5% (n = 11/76) in two consequences, and in 3.9% (n = 3/76) in three consequences. There was no significant association between focus-positive CT scans and mortality (p = 0.81). CONCLUSION: In this population of septic patients in medical intensive care, microbiological analysis complemented CT findings. Both clinical and laboratory parameters were not predictive of CT findings. While therapeutic consequences of CT findings in this study population underline the role of CT for decision making in septic patients, CT findings do not predict patient outcomes in this retrospective analysis.

Early Diagnosis and Prediction of Death Risk in Patients with Sepsis by Combined Detection of Serum PCT, BNP, Lactic Acid, and Apache II Score.

In order to investigate the expression levels of procalcitonin (PCT), B-type brain natriuretic peptide (BNP), and lactic acid (Lac) in serum of patients with sepsis, a retrospective analysis is conducted. 80 sepsis patients admitted to the ICU of our hospital from January 2019 to June 2020 are selected, and the application value of these factors combined with Apache II score in early diagnosis and prediction of death risk is analyzed. All patients are classified into survival group (n = 57) and death group (n = 23), and examined by blood routine. Lac, PCT, and BNP, and the serum PCT, BNP, and Lac levels were compared between the nonsepsis group and the control group. Furthermore, Acute Physiology and Chronic Health Status scoring System II (Apache II) is applied to evaluate the score difference between the sepsis group and the control group. The ROC curve demonstrates that PCT, BNP, and Lac combined with Apache II score can obtain high value for early diagnosis of sepsis. Compared with nonsepsis patients, the scores of serum Lac, PCT, and BNP and Apache II are significantly higher in sepsis patients. It is clearly evident that the combined detection of those indicators is valuable for early diagnosis and prediction of death, and will be suitable for widespread clinical application.

The ability of inflammatory markers to recognize infection in cancer patients with fever at admission.

Infection is one of the main causes of death in cancer patients. Accurate identification of fever caused by infection could avoid unnecessary antibiotic treatment and hospitalization. This study evaluated the diagnostic value of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and other commonly used inflammatory markers in suspected infected adult cancer patients with fever, for better use of antibiotics. This research retrospective analyzed the clinical data of 102 adult cancer patients with fever and compared the serum levels of commonly used inflammatory markers for different fever reasons. Receiver-operating characteristic (ROC) curve and logistic regression analyses were performed. In adult cancer patients with fever, the serum PCT, CRP, IL-6, and IL-10 levels of infected patients were significantly higher than uninfected patients (median 1.19 ng/ml vs 0.14 ng/ml, 93.11 mg/l vs 56.55 mg/l, 123.74 pg/ml vs 47.35 pg/ml, 8.74 pg/ml vs 3.22 pg/ml; Mann-Whitney p = 0.000, p = 0.009, p = 0.004, p = 0.000, respectively). The ROC area under the curve(AUC) was 0.769 (95% confidence interval (CI) 0.681-0.857; p = 0.000) for PCT, 0.664 (95% CI 0.554-0.775; p = 0.009) for CRP, 0.681(95% CI 0.576-0.785; p = 0.004) for IL-6, and 0.731(95% CI 0.627-0.834; p = 0.000) for IL-10. PCT had specificity of 96.67% and positive predictive value (PPV) of 97.6%, when the cut-off value is set as 0.69 ng/ml. The serum IL-6 and IL-10 levels also had significant differences between the infected and uninfected cancer patients with advanced disease (median 128.92 pg/ml vs 36.40 pg/ml, 8.05 pg/ml vs 2.92 pg/ml; Mann-Whitney p = 0.003, p = 0.001, respectively). For the patients with neutropenia, IL-6 and IL-10 had higher AUC of 0.811 and 0.928, respectively. With a cut-off of 9.10 pg/ml, IL-10 had the highest sensitivity 83.33% and specificity 100%. In adult cancer patients, PCT had the best performance compared to CRP, IL-6, and IL-10 in differentiating infected from uninfected causes of fever, with high specificity and PPV. IL-6 and IL-10 might be useful in cancer patients with severe bloodstream infections and advanced disease. However, for patients with neutropenia, IL-10 might be more valuable than PCT in diagnosing infection.

Calprotectin: The Link Between Acute Lung Injury and Gastrointestinal Injury in Covid-19: Ban or Boon.

The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and associated hyper-inflammation due to exaggerated immune response. Different experimental and clinical studies revealed that many biomarkers could be used to determine the Covid-19 severity, such as Ddimer, procalcitonin, C-reaction protein (CRP), IL-6, and ferritin. Calprotectin (CP) is associated with intestinal inflammation, intestinal injury, and different respiratory diseases such as cystic fibrosis. Thus, CP might be a possible biomarker linking intestinal injury and acute lung injury (ALI) in Covid-19. Therefore, this study aimed to find a potential role of CP regarding GITI and ALI in Covid-19. CP is a complex protein consisting of S100A8 and S100A9, belonging to the Ca+2-binding proteins S100 family abundant in the cytosol of neutrophils and expressed on the monocyte membranes, macrophages, and intestinal epithelial cells. CP is a proinflammatory protein that acts through activation of the receptor for the advanced glycation end product (RAGE) and toll-like receptor 4 (TLR4). CP is a biomarker of neutrophil activation and is released following the turnover of neutrophils. CP could be controversial; it increases airway inflammation or protects lung and airway epithelium from an exaggerated immune response. Therefore, a high level of CP in different respiratory disorders might be protective and compensate against abnormal immune responses. CP level is high in Covid-19 and correlated with Covid-19 severity and oxygen demand due to activation of proinflammatory cytokines and inflammatory signaling pathways. Therefore, CP level is elevated in both ALI and intestinal inflammation so that it could be a potential biomarker that links the respiratory and intestinal injury in Covid-19.

The predictive value of procalcitonin combined with C-reactive protein and D dimer in moderately severe and severe acute pancreatitis.

OBJECTIVE: The objective of this study is to investigate the predictive value of a parametric model constructed by using procalcitonin, C-reactive protein (CRP) and D dimer within 48 h after admission in moderately severe and severe acute pancreatitis. METHODS: A total of 238 patients were enrolled, of which 170 patients were moderately severe and severe acute pancreatitis (MSAP+SAP). The concentrations of procalcitonin, CRP and D dimer within 48 h after admission were obtained. The predictive value of the parametric model, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), Ranson score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, modified Marshall score and systemic inflammatory response syndrome (SIRS) score of all patients was calculated and compared. RESULTS: The area under receiver operator characteristic curve, sensitivity, specificity, Youden index and critical value of the parametric model for predicting MSAP+SAP were 0.853 (95% CI, 0.804-0.903), 84.71%, 70.59%, 55.30% and 0.2833, respectively. The sensitivity of the parametric model was higher than that of MCTSI (84.00%), Ranson score (73.53%), BISAP (56.47%), APACHE II score (27.65%), modified Marshall score (17.06%) and SIRS score (78.24%); the specificity of it were higher than that of MCTSI (52.94%) and Ranson score (67.65%), but lower than BISAP (73.53%), APACHE II score (76.47%), modified Marshall score (100%)and SIRS score (100.00%). CONCLUSION: The parametric model constructed by using procalcitonin 48 h, CRP 48 h and D dimer 48 h can be regarded as an evaluation model for predicting moderately severe and severe acute pancreatitis.

MALAT1 regulates PCT expression in sepsis patients through the miR-125b/STAT3 axis.

BACKGROUND: Procalcitonin (PCT) is an important marker in diagnosing sepsis. However, some other diseases can also cause an increase in PCT. PCT still has some limitations in the clinical application of diagnosing sepsis. Therefore, it is of great significance to clarify the regulatory mechanism of PCT expression in sepsis and provide new therapeutic targets for sepsis. METHODS: Blood samples from clinical patients were collected, and peripheral blood monocytes were isolated. Bioinformatics was performed to find the ceRNA regulatory network of STAT3/PCT. MALAT1 and miR-125b were detected by qRT-PCR. MALAT1 was located by fluorescence in situ hybridization (FISH) in U937 cells, and the regulatory relationship between MALAT1, miR-125b, and STAT3 was verified by double luciferase activity report and RNA pull-down assay. U937 cells were transfected with miR-125b, and the effects of the MALAT1/miR-125b/STAT3 pathway on gene and protein secretion levels of PCT were verified by qRT-PCR, western blot, and ELISA. RESULTS: In the serum of sepsis patients and lipopolysaccharide(LPS)-induced U937 cells, MALAT1, STAT3, and PCT gene expression levels were significantly increased, while miR-125b expression level was decreased. FISH results showed that the MALAT1 transcript was mainly located in the nucleus. The double luciferase activity report and RNA pull-down assay results suggested a targeted regulatory relationship between MALAT1, miR-125b, and STAT3. LPS-induced U937 cells transfection with MALAT1 siRNA decreased STAT3 protein expression and phosphorylation level and the expression of PCT. Co-transfection with miR-125b inhibitor effectively reversed this phenomenon. CONCLUSIONS: MALAT1 could upregulate the expressions of STAT3 and PCT by targeted adsorption of miR-125b.

[The role of transferrin receptor CD71 as a diagnostic and prognostic biomarker in sepsis].

OBJECTIVE: To find new biomarkers for the diagnosis and prognosis of sepsis through analyzing the differential expression protein in sepsis by proteomics and bioinformatics analysis and enzyme linked immunosorbent assay (ELISA). METHODS: Patients with sepsis admitted to the emergency department of the Affiliated Hospital of Southwest Medical University from January to December 2019 were enrolled. And meanwhile, healthy volunteers who had normal physical examinations were included as the control group. Blood samples from two groups were collected. The samples were randomly selected for the protein concentration by data independent acquisition (DIA). Bioinformatics method was used in differentially expressed proteins by gene ontology (GO) pathway, enrichment analyses, groups meta-analysis and survival curves construction. ELISA method was used to verified marker screened. Then the data of transferrin receptor CD71 and the clinical data of procalcitonin (PCT), C-reactive protein (CRP) and blood lactic acid (Lac) were collected to construct receiver operator characteristic curve (ROC curve), and biomarker was screened for diagnostic and prognostic of sepsis. RESULTS: The result of DIA showed that 71 differentially expressed proteins were screened out from sepsis group, 6 proteins were down-regulated and 65 proteins were up-regulated. Those differentially expressed proteins were enriched in the inflammatory response, response to stress, leukocyte migration in the GO pathway and enrichment analyses. The meta-analysis showed that the expression level of CD71 was higher in sepsis group than normal control group [standardized mean difference (SMD) = -0.47, 95% confidence interval (95%CI) was -0.93 to 0.00, P < 0.01], the expression level of CD71 was higher in non-survivor group than survivor group (SMD = -0.44, 95%CI was -0.70 to -0.18, P = 0.63). Survival curve showed that the expression of CD71 was inversely correlated to survival rates, the patients with a lower expression had higher survival rates (P = 0.000 34); the ELISA showed that the level of CD71 was higher in sepsis group than normal control group (nmol/L: 156.83±84.71 vs. 87.99±47.89, P < 0.05), the level of CD71 was higher in non-survivor group than survivor group (nmol/L: 219.63±125.59 vs. 130.97±40.45, P < 0.05). The area under the ROC curve (AUC) of CD71 in diagnostic performance of sepsis was 0.790 (sensitivity was 65.1%, specificity was 90.0%), the AUC of CD71 in prognostic performance of sepsis was 0.744 (sensitivity was 57.1%, specificity was 94.1%); CD71 had a better prognostic performance than PCT (AUC = 0.547, sensitivity was 64.3%, specificity was 55.9%), CRP (AUC = 0.594, sensitivity was 64.3%, specificity was 61.8%), Lac (AUC = 0.540, sensitivity was 42.9%, specificity was 82.4%). CONCLUSIONS: CD71 had a great value of diagnostic and prognostic performance in sepsis, and it was expected to be a potential biomarker for sepsis.

Early kinetics of calprotectin in plasma following inguinal hernia surgery.

Calprotectin is one of the most abundant proteins of neutrophil granulocytes. It is released upon neutrophil activation and is considered a sensitive and clinically useful marker for neutrophil-mediated inflammation, including bacterial infections. However, early kinetics of calprotectin activation following inflammatory activation has hitherto been unknown. The aim of the present study was to determine the early phase of the kinetics of calprotectin, in comparison with the inflammatory markers CRP, IL-6, TNF-α, and procalcitonin, in plasma following a standardized temporary mild inflammatory response, using uncomplicated inguinal hernia surgery as a model. The study cohort consisted of 17 adult patients (15 male and 2 female) undergoing elective surgery for hernia. Values of calprotectin increased significantly at 2 h following surgery, and continued to increase to reach the highest level at 24-36 h after surgery, values still not exceeding upper normal reference level. This contrasts to IL-6 and CRP, for which an elevation was found first later, 4 h and 24-36 h post-surgery, respectively, for IL-6, and CRP. No significant increase was seen for TNF-α, or procalcitonin. The data demonstrate a very rapid and significant but modest increase in calprotectin following induction of mild inflammation, supporting that calprotectin can be useful for early detection of inflammatory response.

Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study.

PURPOSE: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. RESULTS: 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. CONCLUSIONS: Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.

Predictive Value of Heart-Type Fatty Acid-Binding Protein for Mortality Risk in Critically Ill Patients.

Objective: Our study assessed the predictive value of heart-type fatty acid-binding protein (H-FABP) for critically ill patients. Methods: 150 critically ill patients admitted to the emergency department of Beijing Chaoyang Hospital, Capital Medical University, were included in our study from August 2021 to April 2022. Serum H-FABP, procalcitonin (PCT), lactate (LAC), and other markers were determined within 1 h after admission. The Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were calculated. The independent predictors of 28-day mortality in critically ill patients were analyzed by logistic regression, and the receiver operating characteristic curve (ROC) was used to analyze the predictive value for 28-day mortality in critically ill patients. Results: Age, APACHE II, SOFA, GCS, LAC, H-FABP, IL-6, Scr, and D-dimer were significantly different in the nonsurvivor vs. survivor groups (P < 0.05), with H-FABP correlating with cTNI, Scr, PCT, and SOFA scores (P < 0.05). Logistic regression analysis showed that H-FABP, APACHE II, LAC, and age were independent predictors for 28-day mortality in critically ill patients (P < 0.05). The AUC of ROC curve in H-FABP was 0.709 (sensitivity 72.9%, specificity 66.1%, and cut-off 4.35), which was slightly lower than AUC of ROC curve in LAC (AUC 0.750, sensitivity 58.3%, specificity 76.1%, and cut-off 1.95) and APACHE II (AUC 0.731, sensitivity 77.1%, specificity 58.7%, and cut-off 12.5). However, statistically, there was no difference in the diagnostic value of H-FABP compared with the other two indicators (Z 1 = 0.669, P = 0.504; Z 2 = 0.383, P = 0.702). But H-FABP (72.9%) has higher sensitivity than LAC (58.3%). The combined evaluation of H-FABP+APACHE II score (AUC 0.801, sensitivity 71.7%, and specificity 78.2%; Z = 2.612, P = 0.009) had better diagnostic value than H-FABP alone and had high sensitivity (71.7%) and specificity (78.2%). Conclusion: H-FABP, LAC, APACHE II, and age can be used as independent risk factors affecting the prognosis of critically ill patients. Compared with using the above indicators alone, the H-FABP+APACHE II has a high diagnostic value, and the early and rapid evaluation is particularly important for the adjustment of treatment plans and prognosis.

The correlation between the expression of ATF4 and procalcitonin combined with the detection of RET mutation and the pathological stage and clinical prognosis of medullary thyroid carcinoma.

To explore the correlation between the activating transcription factor 4 (ATF4) and procalcitonin (PCT) expressions combined with RET mutation and the pathological staging and clinical prognosis of sporadic medullary thyroid carcinoma (SMTC). Fifty cases (tumor tissue) of SMTC diagnosed by clinicopathology were collected and the patients with nodular goiter were selected as normal control. The RET mutation site was analyzed by detection kit and expressions of PCT and ATF4 in SMTC were analyzed by Western blot and immunohistochemistry. Multiple linear regression was used to analyze the correlation of risk factors (PCT or ATF4 expression, RET mutation, tumor differentiation, SMTC stage, lymphatic metastasis) for 5-year recurrence and survival of SMTC. The ATF4 and PCT expressions were significantly decreased and increased, respectively, with the increase of the SMTC stage. The most frequent mutation of RET gene in cancer tissue was M 22458A in exon 16. The ATF4 and PCT expressions, as well as RET mutation, were significantly associated with a 5-year recurrence, while the ATF4 expression was significantly related to better 5-year survival. ATF4 and PCT expressions combined with RET mutation are related to the clinical prognosis of SMTC and can predict SMTC staging.