Dynamic Changes of G-CSF etc. Nine Cytokines in Mouse Bloodstream Infection Models of Staphylococcus aureus and Klebsiella pneumoniae and their Clinical Performances

AbstractBlood culture has been considered as the gold standard to diagnose the bacterial bloodstream infection, but its long turnaround time gravely obstructed the clinical medication by physicians. Cytokines play an important role in bacterial infection. The purpose of this study was to monitor the kinetic changes of nine cytokines in mouse infection models and to infer their diagnostic value in early infection.MethodsThe mouse bloodstream infection model of Staphylococcus aureus and the other model of Staphylococcus aureus and Klebsiella pneumoniae were constructed respectively, and the dynamic changes of nine cytokines were monitored within 48 hours after infected with 1/2 LD50 bacterial concentration. Cytokines with significant differences between the two groups and PBS control group from 0 to 6 hours after infection were selected for theoretical proof in patient sera that were clearly diagnosed as bloodstream infection. Receiver operating characteristic (ROC) curve analysis was conducted to determine the clinical differentiation of different cytokines.ResultsTwo models of S.aureus and K. pneumoniae bloodstream infection in mice were constructed successfully. In the two mouse models, six of the nine cytokines monitored were different (P<0.05) in each experimental group. In the 121 patient sera samples, three cytokines, IL-6, IL-12p70 and G-CSF in the infection groups and control group had showed differences. In particular, AUC of G-CSF was 0.9051, the accuracy is better than IL-6 for diagnosing the infection. In addition, only G-CSF was significantly different between the two infection groups and in the analysis of ROC curve, AUC is equal to 0.735.ConclusionsG-CSF can not only judge the bacterial infection and non-infection, but also distinguish the infection of S.aureus from K. pneumoniae.

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The Diagnostic Value of Eosinophil Count And Platelet-To-Lymphocyte Ratio In Eosinophilic Gastroenteritis

10.21203/rs.3.rs-1042591/v1 ◽

2021 ◽

Author(s):

Qiong Lin ◽

Renmin Zhou ◽

Hao Wujuan ◽

Zhumeng Ni ◽

Xiaozhong Li

Keyword(s):

Blood Cell ◽

Roc Curve ◽

Diagnostic Value ◽

Eosinophilic Gastroenteritis ◽

Control Group ◽

Platelet To Lymphocyte Ratio ◽

Roc Curve Analysis ◽

Record System ◽

Lymphocyte Ratio ◽

The Difference

Abstract Objective: To evaluate the diagnostic value of eosinophil (EO) count and platelet-to-lymphocyte ratio (PLR) in eosinophilic gastroenteritis (EGE). Methods: In total, 91 patients with EGE and 83 age–sex matched patients without EGE were selected as study subjects during January 2018 to December 2020. Data on blood cell count, and serum, C-reactive protein (CRP), and albumin levels were obtained from the Wuxi children's hospital electronic medical record system; the neutrophil-to-lymphocyte ratio (NLR), PLR, and CRP-to-albumin ratio (CAR) in the peripheral blood were recorded. Independent sample t-test, non-parametric test, or χ2 test was used according the data type to compare the difference between two groups, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value for EGE. Results: The EO counts and PLR were significantly higher in the EGE group than those in the control group, whereas differences in the white blood cell, lymphocyte, neutrophil, and platelet counts, and the CRP level, NLR, and CAR were not significant. After treatment(Corticosteroids, 1mg/kg.d, lasting for 2 weeks）, the EO counts and PLR in the EGE group decreased gradually and the difference was significant. The diagnostic value of EO counts and PLR was determined with an area under the ROC curve as 0.756 and 0.616, sensitivity was 75.00% and 34.29%, and specificity was 74.29% and 92.31%, respectively. Conclusions EO and PLR represent potential predictive markers for diagnosing EGE.

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Derivation of a Model to Guide Empiric Therapy for Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infection in an Endemic Area

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa070 ◽

2020 ◽

Vol 7 (7) ◽

Author(s):

Gregory Weston ◽

Fathima Jahufar ◽

Nikhil Sharma ◽

Christopher Su ◽

Eran Bellin ◽

...

Keyword(s):

Blood Culture ◽

Klebsiella Pneumoniae ◽

Bloodstream Infection ◽

Tertiary Care ◽

Classification Rule ◽

Control Group ◽

Care Hospital ◽

Clinical Classification ◽

Carbapenem Resistant ◽

Good Ability

Abstract Background Appropriate therapy for carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection (BSI) is often given late in the course of infection, and strategies for identifying CRKP BSI earlier are needed. Methods A retrospective case–control study was performed at a tertiary care hospital, university hospital, and community hospital in Bronx, New York. All participants had a blood culture sent and received an antibiotic within 48 hours of the culture. The case group (n = 163) had a blood culture with CRKP. The control group (n = 178) had a blood culture with carbapenem-susceptible Klebsiella. Data were obtained by electronic or conventional medical record abstraction. A multiple logistic regression model was built to identify associated factors and develop a clinical model for CRKP BSI. Model performance characteristics were estimated using a 10-fold cross-validation analysis. Results A prior nonblood culture with carbapenem-resistant Enterobacteriaceae, skilled nursing facility (SNF) residence, mechanical ventilation, and admission >3 days were strongly associated risk factors. A significant interaction led to development of separate clinical models for subjects admitted <3 days at the time of positive blood culture from those admitted at least 3 days. The derived models had a good ability to discriminate between subjects with and without CRKP BSI. A clinical classification rule to guide therapy can prioritize sensitivity or specificity. Conclusions Prior nonblood cultures showing resistance and exposure to SNF and health care settings are factors associated with carbapenem resistance. The clinical classification rules derived in this work should be validated for ability to guide therapy.

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Imaging of bioluminescent Klebsiella pneumoniae induced pulmonary infection in an immunosuppressed mouse model

Journal of International Medical Research ◽

10.1177/0300060520956473 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052095647

Author(s):

Xing Hu ◽

Yun Cai ◽

Yuhang Wang ◽

Rui Wang ◽

Jin Wang ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Mouse Model ◽

Real Time ◽

Imaging System ◽

Lung Infection ◽

Infection Model ◽

Immunodeficient Mice ◽

Infection Models ◽

Infection Disease ◽

Immunocompetent Mice

Objective To establish a mouse model of bioluminescent Klebsiella pneumoniae-induced lung infection, under different infection states after pretreatment with various dosages of cyclophosphamide (CTX). Methods A K. pneumoniae strain carrying the luxCDABE operon was used to infect immunocompetent mice (intraperitoneal injection of saline at 4 days and 1 day prior to experimental lung infection) and immunodeficient mice (50 mg/kg CTX at 4 days and 50 mg/kg CTX at 1 day prior to lung infection; or 150 mg/kg CTX at 4 days and 100 mg/kg CTX at 1 day prior to lung infection). Disease progression was monitored in living mice using a bioluminescence imaging system. The bioluminescent images, bacterial loads in lungs, blood cytological changes and histopathology of lungs were analysed. Results K. pneumoniae-induced lung infection models were established in mice pretreated with CTX. Different doses of CTX led to different severities of lung infection. Mice pretreated with 150/100 mg/kg CTX were more suitable for real-time monitoring as they had more typical bioluminescent images of lung infection, more obvious changes in the bioluminescent intensity values, more bacterial colonies in the lungs and more distinct pulmonary pathological changes. Conclusions A stable bioluminescent K. pneumonia-induced lung infection model was successfully established in mice pretreated with CTX, which can be semi-quantitatively monitored in real-time.

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Generic Vancomycin Enriches Resistant Subpopulations of Staphylococcus aureus after Exposure in a Neutropenic Mouse Thigh Infection Model

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.05129-11 ◽

2011 ◽

Vol 56 (1) ◽

pp. 243-247 ◽

Cited By ~ 23

Author(s):

Carlos A. Rodriguez ◽

Maria Agudelo ◽

Andres F. Zuluaga ◽

Omar Vesga

Keyword(s):

Staphylococcus Aureus ◽

Population Analysis ◽

Recovery Process ◽

Control Group ◽

Infection Model ◽

Content Type ◽

Sterile Saline ◽

Generic Products ◽

The Impact

ABSTRACTPrevious studies have shown that “bioequivalent” generic products of vancomycin are less effectivein vivoagainstStaphylococcus aureusthan the innovator compound. Considering that suboptimal bactericidal effect has been associated with emergence of resistance, we aimed to assessin vivothe impact of exposure to innovator and generic products of vancomycin onS. aureussusceptibility. A clinical methicillin-resistantS. aureus(MRSA) strain from a liver transplant patient with persistent bacteremia was used for which MIC, minimum bactericidal concentration (MBC), and autolytic properties were determined. Susceptibility was also assessed by determining a population analysis profile (PAP) with vancomycin concentrations from 0 to 5 mg/liter. ICR neutropenic mice were inoculated in each thigh with ∼7.0 log10CFU. Treatment with the different vancomycin products (innovator and three generics; 1,200 mg/kg of body weight/day every 3 h) started 2 h later while the control group received sterile saline. After 24 h, mice were euthanized, and the thigh homogenates were plated. Recovered colonies were reinoculated to new groups of animals, and the exposure-recovery process was repeated until 12 cycles were completed. The evolution of resistance was assessed by PAP after cycles 5, 10, 11, and 12. The initial isolate displayed reduced autolysis and higher resistance frequencies thanS. aureusATCC 29213 but without vancomycin-intermediateS. aureus(VISA) subpopulations. After 12 cycles, innovator vancomycin had significantly reduced resistant subpopulations at 1, 2, and 3 mg/liter, while the generic products had enriched them progressively by orders of magnitude. The great capacity of generic vancomycin to select for less susceptible organisms raises concerns about the role of therapeutic inequivalence of any antimicrobial on the epidemiology of resistance worldwide.

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Diagnostic accuracy of a dynamically increased red blood cell distribution width in very low birth weight infants with serious bacterial infection

Italian Journal of Pediatrics ◽

10.1186/s13052-021-00994-w ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Bin-Fang Guo ◽

Su-Zhen Sun

Keyword(s):

Birth Weight ◽

Bacterial Infection ◽

Preterm Infants ◽

Roc Curve ◽

Very Low Birth Weight ◽

Reference Group ◽

Curve Analysis ◽

Cell Distribution ◽

Roc Curve Analysis ◽

Distribution Width

Abstract Objective Serious bacterial infection (SBI) remains an important cause of morbidity and mortality in preterm infants. The objective of this study was to evaluate the dynamically increased value of the red cell distribution width (RDW) in the diagnosis of SBI. Methods This retrospective study enrolled 334 preterm infants with birth weight less than 1500 g. The initial RDW and the maximum value of RDW during hospitalization were extracted from the MIMIC-III database (version 1.4). Infants were categorized into four groups according to baseline RDW value and ΔRDW (ΔRDW = RDW at maximum- RDW at baseline). Logistic regression analysis was used to assess the risk of developing SBI in each group. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic value of RDW at baseline alone, ΔRDW alone, and in combination. Results Infants with increased RDW at baseline (> 17%) and ΔRDW > 2% exhibited the highest risk of developing SBI, whereas the patients with normal RDW level at baseline (≤ 17%) and ΔRDW≤2% (the reference group) had the lowest risk. This association remained unaltered even after adjustment in multivariable models. Basing on ROC curve analysis, the area under the curve predicted by the combination of RDW at baseline and ΔRDW for SBI was 0.81 (95% CI, 0.76–0.87). Sensitivity and specificity were 78.16 and 72.47% respectively. Conclusions We observed that combination of elevated RDW at baseline and dynamic increases during hospitalization is significantly associated with SBI. Therefore, that combination could be a promising independent diagnostic indicator of SBI in newborns.

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The effect of BKV reactivation on cytokines behavior in kidney transplanted patients

BMC Nephrology ◽

10.1186/s12882-021-02645-y ◽

2022 ◽

Vol 23 (1) ◽

Author(s):

Zahra Rahimi ◽

Ramin Yaghobi ◽

Afsoon Afshari ◽

Jamshid Roozbeh ◽

Mohammad Javad Mokhtari ◽

...

Keyword(s):

Real Time ◽

Roc Curve ◽

Real Time Pcr ◽

Curve Analysis ◽

Expression Level ◽

Control Group ◽

Roc Curve Analysis ◽

Tnf Α ◽

Ifn Γ ◽

Inactive Group

Abstract Background BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. Methods EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. Results The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. Conclusions Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients’ groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.

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Tissue Polypeptide-Specific Antigen (Tps) Immunoassay in the Diagnosis and Clinical Staging of Prostatic Carcinoma. Comparison with Prostate-Specific Antigen (Psa)

The International Journal of Biological Markers ◽

10.1177/172460089701200106 ◽

1997 ◽

Vol 12 (1) ◽

pp. 27-34 ◽

Cited By ~ 5

Author(s):

L. Ceriani ◽

L. Giovanella ◽

M. Salvadore ◽

A.V. Bono ◽

G. Roncari

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Roc Curve ◽

Specific Antigen ◽

Benign Prostatic Hypertrophy ◽

Clinical Staging ◽

Control Group ◽

Roc Curve Analysis ◽

Skeletal Involvement

This experimental study investigated the potential role of Tissue Polypeptide-Specific Antigen (TPS) in comparison with Prostate-Specific Antigen (PSA) in the diagnosis and the clinical and pathological staging of prostate cancer. Serum TPS and PSA levels were determined in 128 patients (pts) with benign prostatic hypertrophy (BPH; Group 1) and in 92 pts with prostate cancer (Group 2). TPS was also measured in a control group of 100 healthy subjects. Normal cutoff values of 85 U/l for TPS and 4 ng/ml for PSA were determined on the basis of ROC curve analysis. The sensitivity, specificity and accuracy in the diagnosis of prostate cancer were 49%, 95% and 76% for TPS, and 84%, 90% and 87% for PSA. The combination of the two markers provided a higher accuracy (88%), improving the sensitivity of PSA, since 47% of patients with normal PSA had pathological levels of TPS. TPS showed an increase in sensitivity from low to higher stages of disease and, in patients with skeletal involvement, from small to larger numbers of bone metastases (Kruskal Wallis p < 0.0001). Nevertheless, TPS serum levels are not useful in the clinical staging of prostate cancer as they have a poorer performance than PSA. TPS was ineffective (ROC curve area=0.68) in predicting extraprostatic disease and demonstrated a reduced ability (area = 0.78) to identify skeletal involvement. Moreover, the combination of the two markers did not significantly improve the performance of PSA alone. The serum concentration of TPS in patients with localized tumors was not related to the degree of tumor cell differentiation evaluated by the Gleason score. Conclusion Our preliminary experience suggests that TPS in association with PSA may be useful at the time of diagnosis of prostate cancer. However, these preliminary data have to be confirmed by larger clinical trials and the role of this association in the clinical setting needs to be analyzed with an adequate evaluation of the cost-effectiveness ratio.

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Prognostic significance of hematopoietic-cell serglycin for survival of hepatocellular carcinoma: a single-center retrospective study

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201020112459 ◽

2020 ◽

Vol 23 ◽

Author(s):

Yue Li ◽

Hongjie Chen ◽

Huiqiong Lu ◽

Zengcheng Zou ◽

Yongwei Li

Keyword(s):

Hepatocellular Carcinoma ◽

Bacterial Infection ◽

Peripheral Blood ◽

Blood Cells ◽

Cox Regression ◽

Prognostic Significance ◽

Control Group ◽

Peripheral Blood Cells ◽

Blood Proteins ◽

Roc Curve Analysis

Aim and Objective: Inflammation-related changes in peripheral blood cells and blood proteins are prognostic factors for survival in hepatocellular carcinoma (HCC), but their usefulness is limited by active bacterial infection. This study investigated whether infection interfered with the predictive value of serglycin, a proteoglycan found in hematopoietic cells, on survival in HCC. Materials and Methods: Patients with hepatitis B virus (HBV)-induced HCC, 100 without and 30 with bacterial infection, and 30 healthy adult controls were enrolled retrospectively. Baseline clinical data collected before treatment with transarterial chemoembolization (TACE) was evaluated and serglycin expression was assayed by flow cytometry. Receiver operating characteristic (ROC) curve analysis identified serglycin cutoff values for patient stratification. Cox regression and Kaplan– Meier analyses were performed to identify predictors of overall survival (OS). Results: Serglycin levels in peripheral blood cells were higher in both groups of HCC patients than in the control group. Cholinesterase, lung metastasis, average neutrophil serglycin fluorescence intensity, and aspartate aminotransferase levels were associated with survival risk. Barcelona Clinic Liver Cancer stage A was associated a good prognosis of OS. Conclusion: The intensity of serglycin fluorescence in peripheral neutrophils was independently predictive of survival in HCC and its value was not limited by bacterial infection. The method presented here is a simple and feasible way to predict prognosis in HCC patients with TACE.

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Early detection of pancreatic ductal adenocarcinoma using abnormal urinary fragmentation ratio of a liver-originated protein.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.4_suppl.214 ◽

2019 ◽

Vol 37 (4_suppl) ◽

pp. 214-214

Author(s):

Motoyasu Kan ◽

Shuichi Mitsunaga ◽

Masafumi Ikeda ◽

Izumi Ohno ◽

Hironobu Tsubouchi ◽

...

Keyword(s):

Roc Curve ◽

Curve Analysis ◽

Control Group ◽

Healthy Controls ◽

Roc Curve Analysis ◽

Protein Fragments ◽

Abnormal Protein ◽

Pdac Tissue ◽

Healthy Control ◽

Fragmentation Ratio

214 Background: Non PDAC tissue-originated proteins are cleaved by proteases derived from PDAC, which can result in abnormal cleavage patterns in the urine of PDAC patients. Urinary proteomic analysis for quantifying the ratios of the abnormal protein fragments to the non-fragmented protein levels in the urine may be useful to distinguish early PDAC from healthy controls. This proof-of-concept study was planned to determine the usefulness of measuring the protein fragments from non PDAC tissue-originated proteins in the urine using the multiple-reaction-monitoring technique (MRM) for discriminating resectable PDAC from healthy controls. Methods: Urinary proteins were digested with trypsin, and resultant peptides were measured by MRM analysis and the ratio of the level of each fragment to the non-fragmented protein level (fragmentation ratio) was calculated. Fragments for which the fragmentation ratios were higher in the PDAC group than those in the healthy group were defined as abnormal protein fragments. The diagnostic capability of each abnormal protein fragment for discriminating cases of PDAC from healthy controls was evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 21 patients with resectable PDAC and 30 healthy control subjects were enrolled in this study. All the PDAC patients were treated by pancreatic resection. Urine samples for this study were collected prior to the surgery from the PDAC patients. The non PDAC tissue-originated protein was determined as a liver-originated protein. The fragmentation ratios for six fragments were found to be higher in the PDAC group as compared to those in the healthy control group, and these fragments were determined as abnormal protein fragments. ROC curve analysis was performed for each of the abnormal fragments to determine the areas under the curve (AUCs) for discriminating cases of PDAC from healthy controls. The best AUC was 0.81 (95% CI, 0.68-0.91). Conclusions: The urinary fragmentation ratios showed the ability to discriminate cases of resectable PDAC from a healthy control group; abnormal fragmentation ratios may be promising, noninvasively measurable biomarkers of early PDAC.

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Exploring digital filters for internal root resorption: how can we improve the diagnosis of small lesions?

Dentomaxillofacial Radiology ◽

10.1259/dmfr.20210314 ◽

2021 ◽

Author(s):

Priscila Fernanda Silveira Tiecher ◽

Nádia Assein Arús ◽

Eduarda Adams Hilgert ◽

Heloisa Emilia Dias da Silveira ◽

Mathias Pante Fontana ◽

...

Keyword(s):

Roc Curve ◽

Root Resorption ◽

Test Group ◽

Control Group ◽

Roc Curve Analysis ◽

Human Teeth ◽

Diagnostic Efficacy ◽

Root Canals ◽

Phosphor Plates ◽

The Impact

Objectives: This study aimed to evaluate the impact of enhancement filters in detecting small simulated internal root resorptions (IRR). Methods: : forty-two extracted human teeth were sectioned, connected, and stored in a dry human jaw and x-rayed with Photostimulable Phosphor Plates (PSPs), composing the control group (CG). In the middle third of the root canals, IRR lesions were simulated using Da Silveira protocol. After, the specimens were x-rayed to create the test group (TG). All images acquired were exported with seven enhancement filters plus the original image. Three examiners used a five-point Likert scale to evaluate the images regarding the presence/absence of IRR. Diagnostic efficacy was assessed from sensitivity and specificity results. Comparison among filters was performed by using receiver operating characteristic (ROC) curve analysis. Results: : moderate values of Kappainterexaminer (0.403–0.620) and high values of Kappa-intraexaminer (0.757–0.915) were observed. The best performance occurred in the CG (p < 0.05). Original images presented the greatest sensitivity and area under the ROC curve (0.595–0.750), while the Endo filter presented the greatest specificity (0.952). Inversion and Pseudo3D images produced the greatest doubt in the diagnosis, significant for CG with the Pseudo-3D filter (p < 0.05). Conclusions: : the Original and ‘Endo’ filters should be chosen as it offers greater diagnostic ability and allows more confidence during the evaluation.

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