The Plasma Level of Leukemia Stem Cell Specific Antigens - CLL1 and TIM3 Are Predictive of Overall Survival in Acute Myeloid Leukemia

Abstract Background: Despite intensive chemotherapy, acute myeloid leukemia (AML) is still associated with significant relapse rate. This was thought to be due to a sub clone of leukemic blasts that was resistant to chemotherapy. This sub clone of resistant blasts were later identified to be leukemic stem cell (LSC). Many studies have demonstrated that high initial load of LSC at diagnosis was associated with relapse and poor overall outcome. This study aimed to use a clinically practical method - ELISA to identify plasma biomarkers that are closely related to LSC and study their predictive value in term of complete remission (CR), relapse, and overall survival. Method: Peripheral blood of 27 newly diagnosed AML patients were collected at diagnosis. Plasma component of the blood was separate from cellular component using Ficoll separation method. 9 biomarkers were shortlisted based on surface antigens of LSC that were commonly reported in literature as well as genes that were reported to be highly expressed in LSC. These are CD25, CD32, CD96, CD123, TIM3, CLL-1, HCK, FLT3 and WT1. Commercially available ELISA kits with high sensitivity and specificity to these 9 human biomarkers were sourced. All 9 biomarkers were measured on 80 normal blood donors' plasma to use as control and to establish the normal range (Mean+/-2SD). The plasma of the 27 study subjects was measured in duplicate for all 9 biomarkers. ROC curve analysis was done in relation to complete remission, relapse, and survival outcome on all 9 candidates biomarkers. Results: A total 27 newly diagnosed AML patients with curative intent were included in this analysis. Median age for this cohort was 41 years old (range: 22-70). Induction death rate 14.8% (n=4), and complete remission (CR) rate of 77.8%. A total of 8 relapsed refractory cases and 6 deaths were observed over the median follow-up of 10.2 months (range: 0.6-31.2). ROC curve analysis was carried out on all 9 candidates plasma biomarkers, CLL-1 and TIM3 came out to be of significant predictive value of survival outcome. No biomarker was found to be predictive of relapse or CR. ROC curve analysis of plasma CLL-1 level in relation to survival outcome showed an AUC of 0.77 with a plasma cut-off level of 54pg/ml giving the best discriminative result. Chi-square test using this cut off level for survival outcome showed a better survival in patients with plasma CLL-1 level of <54pg/ml (p= 0.001). This cut-off level gave a sensitivity of 83.3% and a specificity of 85.7%, with a high negative predictive value (NPV) of 94.7% but moderate positive predictive value (PPV) of 62.5%. Using this cut-off level to predict CR also showed a significant result (50% CR rate for those with plasma CLL-1 of >54 pg/ml compared to 89.5% in patients with <54pg/ml, p=0.024). Survival function analysis using this cut-off level showed a significantly prolonged survival in patients with plasma CLL-1 level of <54pg/ml with mean survival of 29.63 months (95%CI: 26.70-32.56) as compared to those with plasma CLL-1 level of >54pg/ml (Mean survival: 8.1 months, 95%CI:3.2-13.0). Cox-regression analysis on overall survival showed a significantly high Hazard Ratio of 18.3 for plasma CLL-1 level >54pg/ml (p=0.09, 95%CI:2.09-160.2), see the figure 1 below. ROC curve analysis of plasma TIM3 level in relation to survival outcome revealed an AUC of 0.73 with a plasma cut-off level of 615pg/ml to be the best discriminative cut-off. Chi-square test using this cut-off level for survival outcome showed significant better survival in patients with plasma TIM3 level of <615pg/ml (p=0.016). This cut-off level gave a sensitivity of 83.3% and a specificity of 71.43% with high NPV of 93.75% but a rather low PPV of 45.45%. Survival function analysis again confirmed a much longer mean survival in patients with plasma TIM3 level of <615pg/ml (Mean survival: 29.2 months, 95%CI:25.5-32.9) as compared to TIM3 level of >615pg/ml (Mean survival: 13.8 months, 95%CI:7.2-20.4), p=0.014. Cox-regression analysis again showed a significant Hazard Ratio of 9.2 for plasma TIM3 level of >615pg/ml (p=0.043, 95%CI:1.01-78.7), see figure 2 below. Conclusion: A raised plasma CLL-1 level of more than 54pg/ml and TIM3 level of more than 615pg/ml were predictive of survival outcome in this small cohort of AML patients who underwent curative chemotherapy. A larger cohort of AML patients would be needed to confirm this novel finding. Disclosures No relevant conflicts of interest to declare.

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Baseline hemoglobin <11.0 g/dL has stronger prognostic value than anemia status in nasopharynx cancers treated with chemoradiotherapy

The International Journal of Biological Markers ◽

10.1177/1724600818821688 ◽

2019 ◽

Vol 34 (2) ◽

pp. 139-147 ◽

Cited By ~ 4

Author(s):

Erkan Topkan ◽

Nur Yücel Ekici ◽

Yurday Ozdemir ◽

Ali Ayberk Besen ◽

Berna Akkus Yildirim ◽

...

Keyword(s):

Overall Survival ◽

Nasopharyngeal Carcinoma ◽

Roc Curve ◽

Multivariate Analyses ◽

Progression Free Survival ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Free Survival ◽

Pre Treatment ◽

Baseline Hemoglobin

Background: To retrospectively investigate the influence of pretreatment anemia and hemoglobin levels on the survival of nasopharyngeal carcinoma patients treated with concurrent chemoradiotherapy (C-CRT). Methods: A total of 149 nasopharyngeal carcinoma patients who received C-CRT were included. All patients had received 70 Gy to the primary tumor plus the involved lymph nodes, and 59.4 Gy and 54 Gy to the intermediate- and low-risk neck regions concurrent with 1–3 cycles of cisplatin. Patients were dichotomized into non-anemic and anemic (hemoglobin <12 g/dL (women) or <13 g/dL (men)) groups according to their pre-treatment hemoglobin measures. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of a pre-treatment hemoglobin cut-off that impacts outcomes. Potential interactions between baseline anemia status and hemoglobin measures and overall survival, locoregional progression-free survival (LRPFS), and progression-free survival were assessed. Results: Anemia was evident in 36 patients (24.1%), which was related to significantly shorter overall survival ( P=0.007), LRPFS ( P<0.021), and progression-free survival ( P=0.003) times; all three endpoints retained significance in multivariate analyses ( P<0.05, for each). A baseline hemoglobin value of 11.0 g/dL exhibited significant association with outcomes in ROC curve analysis: hemoglobin <11.0 g/dL (N=26) was linked with shorter median overall survival ( P<0.001), LRPFS ( P=0.004), and progression-free survival ( P<0.001) times, which also retained significance for all three endpoints in multivariate analyses and suggested a stronger prognostic worth for the hemoglobin <11.0 g/dL cut-off value than the anemia status. Conclusion: Pre-C-CRT hemoglobin <11.0 g/dL has a stronger prognostic worth than the anemia status with regard to LRPFS, progression-free survival, and overall survival for nasopharyngeal carcinoma patients.

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Identification and Validation of Two Lung Adenocarcinoma-Development Characteristic Gene Sets for Diagnosing Lung Adenocarcinoma and Predicting Prognosis

Frontiers in Genetics ◽

10.3389/fgene.2020.565206 ◽

2020 ◽

Vol 11 ◽

Author(s):

Cheng Liu ◽

Xiang Li ◽

Hua Shao ◽

Dan Li

Keyword(s):

Lung Adenocarcinoma ◽

Roc Curve ◽

Curve Analysis ◽

Functional Enrichment ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

Gene Set ◽

Gene Sets ◽

Development Characteristic ◽

Score Systems

Background: Lung adenocarcinoma (LUAD) is one of the main types of lung cancer. Because of its low early diagnosis rate, poor late prognosis, and high mortality, it is of great significance to find biomarkers for diagnosis and prognosis.Methods: Five hundred and twelve LUADs from The Cancer Genome Atlas were used for differential expression analysis and short time-series expression miner (STEM) analysis to identify the LUAD-development characteristic genes. Survival analysis was used to identify the LUAD-unfavorable genes and LUAD-favorable genes. Gene set variation analysis (GSVA) was used to score individual samples against the two gene sets. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate Cox regression analysis were used to explore the diagnostic and prognostic ability of the two GSVA score systems. Two independent data sets from Gene Expression Omnibus (GEO) were used for verifying the results. Functional enrichment analysis was used to explore the potential biological functions of LUAD-unfavorable genes.Results: With the development of LUAD, 185 differentially expressed genes (DEGs) were gradually upregulated, of which 84 genes were associated with LUAD survival and named as LUAD-unfavorable gene set. While 237 DEGs were gradually downregulated, of which 39 genes were associated with LUAD survival and named as LUAD-favorable gene set. ROC curve analysis and univariate/multivariate Cox proportional hazards analyses indicated both of LUAD-unfavorable GSVA score and LUAD-favorable GSVA score were a biomarker of LUAD. Moreover, both of these two GSVA score systems were an independent factor for LUAD prognosis. The LUAD-unfavorable genes were significantly involved in p53 signaling pathway, Oocyte meiosis, and Cell cycle.Conclusion: We identified and validated two LUAD-development characteristic gene sets that not only have diagnostic value but also prognostic value. It may provide new insight for further research on LUAD.

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Combine preoperative estimation of serum thyroglobulin and ACR-thyroid imaging reporting and data system scoring could accurately define malignant thyroid nodules

International Surgery Journal ◽

10.18203/2349-2902.isj20205866 ◽

2020 ◽

Vol 8 (1) ◽

pp. 32

Author(s):

Waseem A. Shoda

Keyword(s):

Roc Curve ◽

Predictive Value ◽

Thyroid Nodules ◽

Curve Analysis ◽

Data System ◽

Operating Characteristics ◽

Roc Curve Analysis ◽

Serum Thyroglobulin ◽

Thyroid Imaging ◽

Significant Difference

Background: Evaluation of diagnostic ability of preoperative estimation of serum thyroglobulin (TG) to detect malignant thyroid nodules (TN) in comparison to the American College of Radiology, Thyroid imaging reporting and data system (ACR-TIRADS), fine needle aspiration cytology (FNAC) and intraoperative frozen section (IO-FS).Methods: 34 patients with ACR-TIRADS 2-4 TN were evaluated preoperatively for identification of malignancy and all underwent total thyroidectomy with bilateral neck block dissection if indicated. Results of preoperative investigations were statistically analyzed using the Receiver operating characteristics (ROC) curve analysis as predictors for malignancy in comparison to postoperative paraffin sections.Results: Preoperative serum TG levels had 100% sensitivity and negative predictive value, while ACR-TIRADS scoring had 100% specificity and positive predictive value with accuracy rates of 95.35% and 97.67% for TG and TIRADS, respectively. ROC curve analysis defined preoperative ACR-TIRADS class and serum TG as highly diagnostic than FNAC for defining malignancy with non-significant difference between areas under curve for TIRADS and TG. For cases had intermediate risk of malignancy on TIRADS, IO-FS had missed 3, FNAC missed 4, while serum TG levels were very high in the 13 cases and were defined by ROC curve as the only significant predictor for malignancy.Conclusions: Preoperative estimation of serum TG showed higher diagnostic validity than FNAC, high predictability of cancer and ability to verify the intermediate findings on TIRADS. Combined preoperative TIRADS and TG estimation could accurately discriminate malignant TN with high accuracy and spare the need for preoperative FNAC or IO-FS.

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Construction on of a Ferroptosis-Related lncRNA-Based Model to Improve the Prognostic Evaluation of Gastric Cancer Patients Based on Bioinformatics

Frontiers in Genetics ◽

10.3389/fgene.2021.739470 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiahui Pan ◽

Xinyue Zhang ◽

Xuedong Fang ◽

Zhuoyuan Xin

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Roc Curve ◽

Cox Regression ◽

Risk Group ◽

Survival Curve ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

Gastric Cancer Patients

BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.

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P204 Re-established CRP cut-off in UC; it may be a better predictor of mucosal remission

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.333 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S240-S240

Author(s):

O K Bakkaloglu ◽

T Eskazan ◽

S Bozcan ◽

S Yıldırım ◽

E A Kurt ◽

...

Keyword(s):

Ulcerative Colitis ◽

Positive Predictive Value ◽

Roc Curve ◽

Predictive Value ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Predictive Values ◽

Mucosal Disease ◽

Mayo Score ◽

Montreal Classification

Abstract Background Although faecal calprotectin can predict mucosal remission in ulcerative colitis, the CRP level in this context is insufficient and frequently stay under the current cut off level. While some patients with active mucosal disease have normal CRP levels most patients in mucosal remission have much lower CRP levels. The aim of this study is to define CRP cut off levels in the prediction of mucosal remission, considering both extensiveness and severity, in ulcerative colitis. Methods We retrospectively reviewed colonoscopy reports of ulcerative colitis patients (who are not on any steroid treatment at that time) which were performed between December 2016 and March 2019 and also their CRP levels which were obtained at the same week of the colonoscopy examination. We excluded the data of patients with any other possible cause of inflammation or infection at the time of laboratory assessment. Degree of mucosal disease at colonoscopy was evaluated according to endoscopic Mayo score. Mucosal remission was defined as endoscopic Mayo score 0 or 1. The extent of mucosal inflammation was classified according to Montreal classification. The CRP level with optimal sensitivity and specificity for mucosal remission prediction was assessed by ROC curve analysis and positive and negative predictive values were also calculated. Results A total of 331 colonoscopy reports of 260 patients (122 m, 138 f) were involved in this study. There were no significant differences between ages of patients when compared with ex, and Montreal classification and we did not find any correlation between age and CRP levels. Sensitivity, specificity, positive predictive value and negative predictive values for 5 mg/l, 3 mg /l and 2 mg/l are summarised in Table 1. CRP levels which predict Mayo 0 disease, mucosal remission (Mayo 0–1) and Mayo 3 disease are shown in Table 2. At the ROC curve analysis, we found that CRP level of approximately 2.9 mg/l can predict mucosal remission with a 77% sensitivity and % 80 specificity in all examinations without grouping into a separate segmental disease. For subgroups with Montreal E1, E2 and E3 ROC curve analysis suggested 1,8 mg/l (sn. 84%, sp. 90%), 2,7 mg/l (sn. 75%, sp. 75%) and 3 mg/l (sn. 80%, sp. 80%) CRP levels can be used for prediction of mucosal remission respectively (Table 3). It is important to emphasise that 30% of all patients with Mayo 3 colonoscopy and further 23% of patients with Montreal E3–Mayo 3 activity have CRP levels below the regular cut-off value of 5 mg/l. Conclusion CRP cut-off level of approximately 2.9 mg/l can predict mucosal remission in ulcerative colitis better than standard cut-off of 5 mg/l which has a low positive predictive value and specificity even at extended and active mucosal disease.

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Predictive value of plasma parameters in the risk of postpartum ketosis in dairy cows

Journal of Veterinary Research ◽

10.1515/jvetres-2017-0011 ◽

2017 ◽

Vol 61 (1) ◽

pp. 91-95 ◽

Cited By ~ 7

Author(s):

Yu Cao ◽

Jiang Zhang ◽

Wei Yang ◽

Cheng Xia ◽

Hong-You Zhang ◽

...

Keyword(s):

Dairy Cows ◽

Roc Curve ◽

Predictive Value ◽

Curve Analysis ◽

Paraoxonase 1 ◽

Roc Curve Analysis ◽

Plasma Parameters ◽

Holstein Friesian ◽

Plasma Activity ◽

Friesian Cows

AbstractIntroduction:The predictive value of selected parameters in the risk of ketosis and fatty liver in dairy cows was determined.Material and Methods:In total, 21 control and 17 ketotic Holstein Friesian cows with a β-hydroxybutyrate (BHBA) concentration of 1.20 mmol/L as a cut-off point were selected. The risk prediction thresholds for ketosis were determined by receiver operating characteristic (ROC) curve analysis.Results:In the ketosis group, paraoxonase-1 (PON-1) activity and concentration of PON-1 and glucose (GLU) were decreased, and aminotransferase (AST) activity as well as BHBA and non-esterified fatty acid (NEFA) contents were increased. The plasma activity and concentration of PON-1 were significantly positively correlated with the level of plasma GLU. The plasma activity and concentration of PON-1 were significantly negatively correlated with the levels of AST and BHBA. According to ROC curve analysis, warning indexes of ketosis were: plasma PON-1 concentration of 46.79 nmol/L, GLU concentration of 3.04 mmol/L, AST concentration of 100 U/L, and NEFA concentration of 0.82 mmol/L.Conclusion:This study showed that the levels of PON-1, GLU, AST, and NEFA could be used as indicators to predict the risk of ketosis in dairy cows.

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Global longitudinal strain and chronic kidney disease prognostic impact on acute coronary syndrome

European Heart Journal ◽

10.1093/ehjci/ehaa946.1622 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A.R Morgado Gomes ◽

D Campos ◽

C Saleiro ◽

J Gameiro Lopes ◽

J.P Sousa ◽

...

Keyword(s):

Regression Analysis ◽

Roc Curve ◽

Cox Regression ◽

Left Ventricular ◽

Curve Analysis ◽

Left Ventricular Ejection ◽

Roc Curve Analysis ◽

Ventricular Ejection Fraction ◽

Cox Regression Analysis ◽

Coronary Syndrome

Abstract Background Impaired left ventricular ejection fraction (LVEF) and chronic kidney disease (CKD) have been associated with poorer outcomes in acute coronary syndrome (ACS). Increasing evidence on global left ventricular longitudinal strain (GLS) suggests superiority over left ventricular ejection fraction (LVEF) in risk stratification. Methods This study was based on a retrospective analysis of consecutive patients admitted to a Coronary Care Unit between 2009 and 2016. Baseline characteristics and echocardiographic parameters, including LVEF, were assessed. For each patient, a two-dimensional speckle tracking of the left ventricle was assessed and average GLS was calculated using 2, 3 and 4-chamber views. Blood creatinine was measured during hospital stay and used to estimate glomerular filtration rate (GFR) with Modification of Diet in Renal Disease (MDRD) equation. A cox regression analysis was performed to determine mortality prediction value of average GLS, LVEF and GFR in this population. Receiver operating characteristic (ROC) curve analysis was conducted and area under the curve (AUC) was estimated. Results A total of 85 patients (66.7±12.7 years old; 78.8% males) were enrolled. LVEF mean was 49.4±9.8% and average GLS was −16.0±4.0%. GFR median was 80.0±48.9 ml/min/1.73m2. In cox regression analysis, worse average GLS was associated with greater mortality (HR 0.721; 95% CI 0.599–0.867; P=0.001). GFR was inversely related to death (HR 0.967; 95% CI 0.944–0.991, P=0.008). In cox regression analysis using average GLS and GFR as covariates, both proved to be independent predictors of mortality (for average GLS, HR 0.748; 95% CI 0.610–0.918, P=0.005; for GFR, HR 0.974; 95% CI 0.949–0.999; P=0.044). The AUC of average GLS to predict mortality was 0.78 (P<0.001, sensitivity 50.7% and specificity 100%) and for average GLS and GFR combined was 0.85 (P<0.001, sensitivity 84.0% and specificity 77.8%). Although LVEF proved to be a mortality predictor, the AUC obtained by ROC curve analysis was inferior to average GLS, with statistical significance (P=0.043). Conclusions GLS and CKD proved to be independent predictors of mortality in ACS patients. GLS showed superiority when compared to LVEF in risk stratification and in the future it might replace LVEF. The model combining GLS and GFR emphasized the increased risk of CKD patients and how they should be seen as high-risk patients. ROC curve analysis Funding Acknowledgement Type of funding source: None

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Immature platelet fraction is a strong predictor of adverse cardiovascular events in patients with acute coronary syndrome. Results of the ISAR-REACT 5 reticulated platelet substudy

European Heart Journal ◽

10.1093/ehjci/ehaa946.1668 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

D Bongiovanni ◽

K Mayer ◽

N Schreiner ◽

V Karschin ◽

I Wustrow ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Coronary Syndrome ◽

Primary Endpoint ◽

Roc Curve ◽

Cardiovascular Events ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Immature Platelet Fraction

Abstract Introduction Reticulated or immature Platelets are pro-thrombotic RNA-rich young platelets, which have been reported to correlate with adverse events in several pathological settings including coronary artery disease. However, the predictive value of this subgroup of platelets in patients with acute coronary syndrome treated with the potent novel P2Y12 inhibitors prasugrel or ticagrelor has not been investigated yet. Moreover, their role as predictors of major bleeding is unclear. Purpose The primary aim of this prespecified reticulated platelet ISAR-REACT-5 substudy was to evaluate the immature platelet fraction (IPF%) in peripheral blood as a predictor of the composite primary endpoint consisting of death, myocardial infarction, or stroke at one year after randomization in patients with acute coronary syndrome. Methods IPF was assessed in the first 24h after randomization using a fully automated system and correlated to the incidence of the primary endpoint. All patients with available IPF values were included. The Sysmex system uses two fluorescent dyes to stain platelet RNA and a computer algorithm (Sysmex IPF Master) discriminates immature from mature platelets by the intensity of forward scattered light and fluorescence. The immature platelet fraction is displayed as percentage of the total optical platelet count (IPF%). Results IPF values within the first 24h after randomization were available in a total of 506 randomized patients. Baseline characteristics and IPF (median [IQR]) values did not differ between the 2 study groups (IPF: prasugrel 3.9% [2.7–5.8] ticagrelor 3.4% [2.5–5.6] p=0.56). Significantly higher IPF values were observed in patients reaching the primary endpoint (n=55 of 506) independent from the study group (p for interaction= 0.28). ROC-curve analysis revealed a cut-of value of IPF 3.6% for the prediction of death, myocardial infarction or stroke with a Hazard ratio (HR) according to cox-regression analysis of 1.98 (95% CI, 1.15–3.44), P=0.01 (Figure 1A). Interestingly, we also detected a trend for higher major bleedings (BARC 3–5) in patients with elevated IPF values above IPF>4.8% according to ROC-curve analysis (Figure 1B). Conclusion IPF was significantly associated with the primary endpoint in the ISAR-REACT 5 substudy independent from the treatment group and therefore is a promising novel biomarker for the prediction of adverse cardiovascular events in patients with acute coronary syndrome. Figure 1 Funding Acknowledgement Type of funding source: None

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Multiplex Immunoassay of Cytokines for The Short-Term Prognosis Predictive Value of Patients With Acute-on-Chronic Liver Failure

10.21203/rs.3.rs-154337/v1 ◽

2021 ◽

Author(s):

Yongyuan Zheng ◽

Genglin Zhang ◽

Lina Wu ◽

Jing Xiong ◽

Lu Wang ◽

...

Keyword(s):

Overall Survival ◽

Regression Analysis ◽

Hepatitis B ◽

Cox Regression ◽

Curve Analysis ◽

Chronic Liver Failure ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

Multiplex Immunoassay ◽

Kaplan Meier

Abstract Background: Since the systemic inflammation has been found to be associated with disease progression and mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF), the objective of this study was to detect inflammatory factors in ACLF patients by a Luminex-based multiplex immunoassay system for high throughput screening of the cytokine with the most prognostic value.Methods: Luminex-based multiplex immunoassay technology was used to determine the concentrations of 48 cytokines in total at once in serum samples from 40 patients with HBV-ACLF, 30 patients with chronic hepatitis B (CHB) and 25 healthy volunteers as normal controls (NC). Then, the receiver operating characteristic (ROC) curve analysis was applied to evaluate the prognostic prediction accuracy. Besides, Kaplan–Meier curves was used to analyze survival, while the Cox regression analysis to determine the mortality predictors.Results: The level of IL-6, IL-10, IL-15, IL-18, M-CSF, IP-10 and CXCL9 were significantly higher in patients with HBV-ACLF than in either patients with CHB or NC subjects, while the level of EGF, PDGF-AA, PDGF-AB/BB, MDC and sCD40L were significantly lower. The concentrations of IL-6, CXCL9, and IL-15 was higher in non-surviving patients with HBV-ACLF than in surviving patients while MDC was lower. Increased serum IL-6 was positively correlated with disease severity. The ROC curve analysis showed that IL-6 and CXCL-9 accurately predicted 90-day survival in patients with HBV-ACLF, with an accuracy equivalent to those of the Model for End-Stage Liver Disease (MELD), MELD-Na. Kaplan–Meier analysis showed an association between the increase in serum concentration of IL-6 as well as CXCL9 and poor overall survival in patients with HBV-ACLF. Moreover, the multivariate Cox regression analysis showed that only serum IL-6 was an independent predictor of overall survival in patients with HBV-ACLF.Conclusion: Although HBV-related ACLF patients have significantly increased serum levels of multiple cytokines, only serum IL-6 levels could be an independent prognostic biomarker in patients with HBV-ACLF.

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Predictive value of cerebrospinal fluid lactate for the diagnosis and treatment efficacy of post-neurosurgery bacterial meningitis

10.21203/rs.2.18481/v1 ◽

2019 ◽

Author(s):

Yufang Wang ◽

Jingchao Li ◽

Mingli Yao ◽

Lingyan Wang ◽

Bin Ouyang

Keyword(s):

Cerebrospinal Fluid ◽

Linear Regression ◽

Bacterial Meningitis ◽

Roc Curve ◽

Predictive Value ◽

Treatment Efficacy ◽

Curve Analysis ◽

Diagnosis And Treatment ◽

Roc Curve Analysis ◽

Csf Lactate

Abstract Background: Post-neurosurgical bacterial meningitis (PNBM) is a severe complication with high morbidity and mortality. Rapid and accurate diagnosis of PNBM is difficult. Therefore, it is necessary to find more reliable markers to assist the diagnosis. This study aims to evaluate the predictive value of cerebrospinal fluid (CSF) lactate for PNBM diagnosis and treatment efficacy.Methods: Total 105 cases were enrolled in patients with clinically suspected PNBM who underwent neurosurgeries during October 2015 to December 2016. CSF lactate as well as CSF routine and biochemistry test was measured. Receivers operating characteristic (ROC) curve analysis was used to evaluate the diagnostie power of CSF lactate for PNBM. To assess the predictive value of CSF lactate for treatment efficacy, a linear regression was used and tendency diagrams of CSF lactate and glucose for each patient were drawn.Results: Fifty-four of 105 patients were diagnosed with PNBM. CSF lactate level was significantly higher in PNBM than in non-PNBM patients (p < 0.001). The ROC curve analysis showed a great diagnostic power of CSF lactate for PNBM, and the cut-off value was 4.15 mmol/L (AUC = 0.92, sensitivity, 92.6%; specificity, 74.5%). The combination of CSF lactate and glucose showed better diagnostic efficacy (AUC = 0.97, sensitivity, 94.4%; specificity, 90.2%). The linear regression showed thatΔCSF lactate inversely correlated with ΔCSF glucose and directly correlated with ΔCSF leucocyte (both p < 0.001). The tendency diagrams showed CSF lactate a better predictor for PNBM treatment efficacy than CSF glucose.Conclusion: Our study showed CSF lactate had an excellent discriminatory power in distinguishing between PNBM and non-PNBM. The combination of CSF lactate and glucose had a better diagnostic accuracy than other CSF parameters alone. CSF lactate was a reliable predictor of treatment efficacy in PNBM patients.

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