scholarly journals Plasma vanin-1 as a novel biomarker of sepsis for trauma patients: a prospective multicenter cohort study

2020 ◽  
Author(s):  
Hongxiang Lu ◽  
Anqiang Zhang ◽  
Dalin Wen ◽  
Juan Du ◽  
Jianhui Sun ◽  
...  
Keyword(s):  
Cohort Study ◽  
Healthy Volunteers ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
External Validation ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Enzyme Linked Immunosorbent Assay ◽  
Trauma Patients ◽  
Potential Biomarker

Abstract BackgroudVanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 expression can be used to predict traumatic sepsis in an early time.MethodsIn this three-stage prospective cohort study, severe trauma patients admitted to two hospitals from January 2015 to October 2018 were enrolled. Clinical data during hospitalization and APACHE II score were collected. Plasma vanin-1 levels were measured by enzyme linked immunosorbent assay. The associations among variables and traumatic sepsis were identified by logistic regression model. The receiver-operating characteristic curve was analyzed to evaluate the diagnostic efficiency of the selected factors.ResultsA total of 426 trauma patients (22 patients in the discovery cohort, 283 patients in the internal test cohort, and 121 patients in the external validation cohort) and 16 healthy volunteers were enrolled. The plasma vanin-1 level of trauma patients was significantly higher than that of healthy volunteers (P < 0.05), and sepsis patients had higher plasma vanin-1 than non-sepsis patients in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 levels at day 1 after trauma were significantly associated with the incidence of sepsis (OR = 3.92, 95% CI = 2.68–5.72, P = 1.62⊆10− 12). As a predictive biomarker, vanin-1 obtained a better area under the curve (AUC) (0.82, 95% CI = 0.77–0.87) than C-reaction protein (CRP) (0.62, 95% CI = 0.56–0.68, P < 0.0001), procalciton in (PCT) (0.66, 95% CI = 0.60–0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI = 0.65–0.76, P = 6.70⊆10− 3). In addition, the clinical relevance between plasma vanin-1 and traumatic sepsis was validated in the external validation cohort (OR = 4.26, 95% CI = 2.22–8.17, P = 1.28⊆10− 5). The AUC of vanin-1 was 0.83 (95% CI = 0.75–0.89), which was better than that of CRP, PCT, and APACHE II.ConclusionsOur study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis.Trial registrationClinicaltrials.gov Identifier NCT01713205. Registered 24 October 2012.

scholarly journals Improvement of APACHE II score system for disease severity based on XGBoost algorithm

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Luo ◽  
Zhiyu Wang ◽  
Cong Wang
Keyword(s):  
Intensive Care ◽  
Hospital Mortality ◽  
Patient Outcomes ◽  
External Validation ◽  
Apache Ii ◽  
Validation Dataset ◽  
Apache Ii Score ◽  
Severity Scores ◽  
The Impact ◽  
Improve Patient

Abstract Background Prognostication is an essential tool for risk adjustment and decision making in the intensive care units (ICUs). In order to improve patient outcomes, we have been trying to develop a more effective model than Acute Physiology and Chronic Health Evaluation (APACHE) II to measure the severity of the patients in ICUs. The aim of the present study was to provide a mortality prediction model for ICUs patients, and to assess its performance relative to prediction based on the APACHE II scoring system. Methods We used the Medical Information Mart for Intensive Care version III (MIMIC-III) database to build our model. After comparing the APACHE II with 6 typical machine learning (ML) methods, the best performing model was screened for external validation on anther independent dataset. Performance measures were calculated using cross-validation to avoid making biased assessments. The primary outcome was hospital mortality. Finally, we used TreeSHAP algorithm to explain the variable relationships in the extreme gradient boosting algorithm (XGBoost) model. Results We picked out 14 variables with 24,777 cases to form our basic data set. When the variables were the same as those contained in the APACHE II, the accuracy of XGBoost (accuracy: 0.858) was higher than that of APACHE II (accuracy: 0.742) and other algorithms. In addition, it exhibited better calibration properties than other methods, the result in the area under the ROC curve (AUC: 0.76). we then expand the variable set by adding five new variables to improve the performance of our model. The accuracy, precision, recall, F1, and AUC of the XGBoost model increased, and were still higher than other models (0.866, 0.853, 0.870, 0.845, and 0.81, respectively). On the external validation dataset, the AUC was 0.79 and calibration properties were good. Conclusions As compared to conventional severity scores APACHE II, our XGBoost proposal offers improved performance for predicting hospital mortality in ICUs patients. Furthermore, the TreeSHAP can help to enhance the understanding of our model by providing detailed insights into the impact of different features on the disease risk. In sum, our model could help clinicians determine prognosis and improve patient outcomes.

scholarly journals Influencing Factors and Prevention of Sepsis or Acute Kidney Injury in 85 Patients with Severe Trauma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Hong Zhang ◽  
Dan Chen ◽  
Lihua Wang ◽  
Bing Li
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Influencing Factors ◽  
Severe Trauma ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Trauma Patients ◽  
Risk Of Death ◽  
Disturbance Of Consciousness ◽  
Prevention And Treatment

Severe trauma can cause systemic reactions, leading to massive bleeding, shock, asphyxia, and disturbance of consciousness. At the same time, patients with severe trauma are at high risk of sepsis and acute renal injury. The occurrence of complications will increase the difficulty of clinical treatment, improve the mortality rate, and bring heavy physical and mental burdens and economic pressure to patients and their families. It is of great clinical significance to understand the high risk factors of sepsis and AKI and actively formulate prevention and treatment measures. In this study, the clinical data of 85 patients with severe trauma were analyzed by univariate and multivariate logistic regression to identify the risk factors leading to sepsis or AKI and analyze the prevention and treatment strategies. The results showed that multiple injuries, APACHE II score on admission, SOFA score on admission, and mechanical ventilation were independent influencing factors of sepsis in patients with severe trauma, while hemorrhagic shock, APACHE II score on admission, CRRT, and sepsis were independent influencing factors of AKI in patients with severe trauma. Severe trauma patients complicated with sepsis or AKI will increase the risk of death. In the course of treatment, prevention and intervention should be given as far as possible to reduce the incidence of complications.

scholarly journals Aberrant miR-219-5p is correlated with TLR4 and serves as a novel biomarker in patients with multiple organ dysfunction syndrome caused by acute paraquat poisoning

2020 ◽  
Vol 34 ◽  
pp. 205873842097488
Author(s):  
Yunxiang Dai ◽  
Xia Liu ◽  
Yuming Gao
Keyword(s):  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Multiple Organ ◽  
Apache Ii ◽  
Luciferase Reporter ◽  
Apache Ii Score ◽  
Multiple Organ Dysfunction ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
Tnf Α

This study aimed to investigate the clinical significance of serum microRNA-219-5p (miR-219-5p) in patients with multiple organ dysfunction syndrome (MODS) caused by acute paraquat (PQ) poisoning, and its correlation with Toll-like Receptor 4 (TLR4). Luciferase reporter assay was used to investigate in vitro the correlation of miR-219-5p with TLR4. Serum miR-219-5p levels were evaluated by quantitative real-time polymerase chain reaction. Serum levels of TLR4, IL-1β, and TNF-α were measured by Enzyme-linked immune sorbent assay (ELISA). ROC analysis was performed to assess the diagnostic significance, Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-219-5p in MODS patients. TLR4 was a target gene of miR-219-5p and was increased in MODS patients. Serum miR-219-5p level was decreased and negatively correlated with TLR4 level in MODS patients ( r = −0.660, P < 0.001), which had important diagnostic value and negatively correlated with APACHE II score in MODS patients. The miR-219-5p expression was markedly associated with the WBC, ALT, AST, PaCO2, Lac, and APACHE II score. Non-survivals had more patients with low miR-219-5p expression. Patients with low miR-219-5p expression had shorter survival time. MiR-219-5p and APACHE II score were two independently prognostic factors for 28-day survival. MiR-219-5p was negatively correlated with, while TLR4 was positively correlated with the levels of IL-1β and TNF-α. The serum miR-219-5p level may be a potential biomarker for acute PQ-induced MODS diagnosis and prognosis. Furthermore, miR-219-5p may be associated with the progression of MODS by regulating TLR4-related inflammatory response.

scholarly journals Amylase quantification in the terminal Ileum following formation of an Ileostomy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
D. A. Clark ◽  
T. Cuda ◽  
C. Pretorius ◽  
A. Edmundson ◽  
M. Solomon ◽  
...  
Keyword(s):  
Cohort Study ◽  
Small Intestine ◽  
Healthy Volunteers ◽  
Sample Size ◽  
Terminal Ileum ◽  
Pancreatic Surgery ◽  
Reference Range ◽  
Validation Cohort ◽  
Physiological Activity ◽  
Testing Methodology

Abstract Amylase is elevated in the foregut and has been used to confirm anastomotic integrity after pancreatic surgery. The physiological activity of pancreatic enzymes in the ileum has been studied in healthy volunteers but not quantitated with the simple and readily available amylase measurements employed with serum tests. We aim to quantitate the levels of amylase in the terminal ileum. This was a prospective, non-randomised, non-blinded, consecutive cohort study conducted at the Royal Brisbane and Women’s Hospital. Consecutive patients undergoing routine surgery with an ileostomy were invited to participate in the study. Ileostomy effluent was collected and analysed daily for the first 5 post-operative days. This validation cohort included 8 males and 3 females, with a mean age of 49 years. Median daily amylase levels ranged from 4470 U/L to 23,000 U/L, with no specimens falling within the laboratory serum reference range of 40 to 130 U/L. Two specimens were not available on day one post-operative due to complete ileus. The sample size of 11 patients is small but was considered sufficient given that 55 effluent specimens were anticipated for analysis. Amylase levels remain highly elevated as the enzyme transits through the length of the small intestine and measured in the terminal ileum, and can be readily quantitated by the existing testing methodology routinely available.

scholarly journals A Modified TNM Classification for Primary Operable Colorectal Cancer

2020 ◽  
Author(s):  
Chundong Zhang ◽  
Zubing Mei ◽  
Junpeng Pei ◽  
Masanobu Abe ◽  
Xiantao Zeng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Validation Cohort ◽  
Tnm Classification ◽  
Characteristic Curve ◽  
External Validation ◽  
Model Fitting ◽  
Information Criteria ◽  
Stage I ◽  
Internal Validation ◽  
Clinical Benefits

Abstract Background The American Joint Committee on Cancer (AJCC) 8th tumor/node/metastasis (TNM) classification for colorectal cancer (CRC) has limited ability to predict prognosis. Methods We included 45,379 eligible stage I-III CRC patients from the Surveillance, Epidemiology, and End Results Program. Patients were randomly assigned individually to a training (N =31,772) or an internal validation cohort (N =13,607). External validation was performed in 10,902 additional patients. Patients were divided according to T and N stage permutations. Survival analyses were conducted by a Cox proportional hazard model and Kaplan-Meier analysis, with T1N0 as the reference. Area under receiver operating characteristic curve (AUC) and Akaike information criteria (AIC) were applied for prognostic discrimination and model-fitting, respectively. Clinical benefits were further assessed by decision curve analyses. Results We created a modified TNM (mTNM) classification: stages I (T1-2N0-1a), IIA (T1N1b, T2N1b, T3N0), IIB (T1-2N2a-2b, T3N1a-1b, T4aN0), IIC (T3N2a, T4aN1a-2a, T4bN0), IIIA (T3N2b, T4bN1a), IIIB (T4aN2b, T4bN1b), and IIIC (T4bN2a-2b). In the internal validation cohort, compared to the AJCC 8th TNM classification, the mTNM classification showed superior prognostic discrimination (AUC = 0.675 vs. 0.667, respectively; two-sided P &lt;0.001) and better model-fitting (AIC = 70,937 vs. 71,238, respectively). Similar findings were obtained in the external validation cohort. Decision curve analyses revealed that the mTNM had superior net benefits over the AJCC 8th TNM classification in the internal and external validation cohorts. Conclusions The mTNM classification provides better prognostic discrimination than AJCC 8th TNM classification, with good applicability in various populations and settings, to help better stratify stage I-III CRC patients into prognostic groups.

scholarly journals CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression

2020 ◽  
Vol 21 (6) ◽  
pp. 2040 ◽  
Author(s):  
Sara Pączek ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Piotr Mroczko ◽  
Agnieszka Kulczyńska-Przybik ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Marker ◽  
Cancer Progression ◽  
Characteristic Curve ◽  
Distant Metastases ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Predictive Values ◽  
Potential Biomarker ◽  
Tumor Stages

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.

Tissue Plasminogen Activator Levels and Risk of Breast Cancer in a Case–Cohort Study on Italian Women: Results from the Moli-sani Study

2020 ◽  
Author(s):  
Simona Costanzo ◽  
Roberta Parisi ◽  
Amalia De Curtis ◽  
Sara Gamba ◽  
Laura Russo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Cox Regression ◽  
Enzyme Linked Immunosorbent Assay ◽  
Potential Biomarker ◽  
Increased Risk ◽  
Tissue Plasminogen ◽  
Incident Cases

Abstract Background Elevated levels of key enzymes of the fibrinolytic system, such as tissue plasminogen activator (tPA), are reported as predictors of poor outcome in cancer patients. Limited information is available about their potential predictive value for breast cancer (BC) risk in the general population. Aim We examined the association of tPA levels with BC risk in a case–cohort study including women from the prospective Moli-sani cohort. Methods A sample of 710 women (mean age: 54.6 ± 12.1 years) was selected as a subcohort and compared with 84 BC cases, in a median follow-up of 4.2 years. Incident cases of BC were validated through medical records. tPA plasma levels were measured using an enzyme-linked immunosorbent assay kit. Hazard ratio (HR) and 95% confidence interval (CI), adjusted for relevant covariates, were estimated by a Cox regression model using the Prentice method. Results Compared with the lowest quartile (<4.9 ng/mL), women in the highest quartile of tPA (>11.2 ng/mL) had increased risk of BC (HRIVvsI: 2.20, 95% CI: 1.13–4.28) after adjusted for age, smoking, education, menopause, and residence. Further adjustment for biochemical markers did not modify this association. The risk of BC increased by 34% for each increase in 1 standard deviation of log-transformed tPA levels (p = 0.046). Elevated levels of tPA were associated mainly with estrogen-receptor-positive BC (2.08, 95% CI: 1.18–3.66). Conclusion Higher levels of tPA, reported to predict cardiovascular risk, are a potential biomarker for BC risk, supporting the hypothesis of a “common soil” linking the pathogenic mechanisms of hormone-dependent tumors and cardiovascular disease.

A urine exosomal circRNA classifier for detection of high-grade prostate cancer at initial biopsy: A multicenter, retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5522-5522
Author(s):  
Liaoyuan Li ◽  
Wen Tao ◽  
Yadi He ◽  
Tao He ◽  
Qing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Validation Cohort ◽  
Characteristic Curve ◽  
Specific Antigen ◽  
Digital Rectal Examination ◽  
Circular Rna ◽  
High Grade ◽  
Training Cohort ◽  
Potential Biomarker ◽  
Initial Biopsy

5522 Background: The low specificity of prostate-specific antigen (PSA) has resulted in the overdiagnosis and overtreatment of clinically indolent prostate cancer (PCa). We aimed to identify a urine exosomal circular RNA (circRNA) classifier that could detect high-grade (Gleason score [GS]7 or greater) PCa. Methods: We did a three-stage study that enrolled eligible participants, including PCa-free men, 45 years or older, scheduled for an initial prostate biopsy due to suspicious digital rectal examination findings and/or PSA levels (limit range, 2.0-20.0 ng/mL), from four hospitals in China. We used RNA sequencing and digital droplet polymerase chain reaction to identify 18 candidate urine exosomal circRNAs that were increased in 11 patients with high-grade PCa compared with 11 case-matched patients with benign prostatic hyperplasia. Using a training cohort of eligible participants, we built a urine exosomal circRNA classifier (Ccirc) to detect high-grade PCa. We then evaluated the classifier in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy in two independent cohorts. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared Ccirc with standard of care (SOC) (ie, PSA level, age, race, and family history). Results: Between June 1, 2016, and July 31, 2019, we recruited 356 participants to the training cohort, and 442 and 325 participants to the two independent validation cohorts. We identified a Ccirc containing five differentially expressed circRNAs (circ_0049335, circ_0056536, circ_0004028, circ_0008475, and circ_0126027) that could detect high-grade PCa. Ccirc showed higher accuracy than SOC to distinguish individuals with high-grade PCa from controls in both the training cohort and the validation cohorts. (AUC 0.831 [95% CI 0.765-0.883] vs 0.724 [0.705-0.852], P = 0.032 in the training cohort; 0.823 [0.762-0.871] vs 0.706 [0.649-0.762], P = 0.007 in validation cohort 1; and 0.878 [0.802-0.943] vs 0.785 [0.701-0.890], P = 0.021 for validation cohort 2). In all three cohorts, Ccirc had higher sensitivity (range 71.6-87.2%) and specificity (82.3-90.7%) than did SOC (sensitivity, 42.3-68.2%; specificity, 40.1-62.3%) to detect high-grade PCa. Using a predefined cut point, 202 of 767 (26.3%) biopsies would have been avoided, missing only 6% of patients with dominant pattern 4 high-risk GS 7 disease. Conclusions: Ccirc is a potential biomarker for high-grade PCa among suspicious men.

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