Complement component C9 as a new biomarker for esophageal adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 19-19 ◽  
Author(s):  
Virendra Joshi ◽  
Alok Shah ◽  
Ian Brown ◽  
Clay Winterford ◽  
Michelle Hill
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Early Stage ◽  
Multiple Reaction Monitoring ◽  
Diagnostic Value ◽  
Complement Component ◽  
Endoscopic Surveillance ◽  
Disease Stage ◽  
Receiver Operating Curve ◽  
Diagnostic Tools ◽  
Serum Glycoprotein

19 Background: Esophageal adenocarcinoma (EAC) continues an upward trend. Mortality rate and treatment costs for EAC are very high overall and significantly increase with disease stage. Diagnosis at early stage (T1) compared to advanced stage (T3) improves 5 year survival from 20% to 80-90%. Endoscopic surveillance has been ineffective in reducing EAC. Therefore the need for better diagnostic tools for early detection.Previously we reported validation of a list of serum glycoprotein biomarker candidates for EAC in an Australian cohort (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Here we further evaluate the serum and tissue expression of top candidate C9 in an independent cohort from the USA. Methods: Serum samples (n=38) and FFPE tissue sections (n=34) were collected from participants with IRB approved protocol, from the Ochsner Clinic undergoing endoscopic surveillance for Barrett’s and esophageal cancer. Serum glycoprotein candidates were measured using lectin magnetic bead array-coupled multiple reaction monitoring assay (Shah et al. 2015 Mol Cell Proteomics. 14:3023-39.). Immunohistochemistry was optimised for complement component C9 antibody. Initial evaluation of 2 different antibodies gave similar results, thereafter, a polyclonal antibody from Sigma Aldrich was used. Staining was assessed by a gastrointestinal pathologist. Results: Specific glycosylated forms of 3 candidate serum biomarkers were confirmed to be significantly different between EAC and benign groups (p<0.05, Kruskal-Wallis). The diagnostic value for the 3 individual markers, complement component C9, gelsolin and alpha-1-antichymotrypsin (Serpin A3) was 0.71 to 0.82 area under the receiver operating curve (AUROC). A multivariate panel consisting of 8 glycoprotein biomarkers achieved AUROC of 0.96, indicative of high diagnostic value. Immunohistochemistry of tissues detected high levels of C9 in BE and EAC compared to normal squamous epithelium. Infiltrated lymphocytes showed variable staining. Conclusions: We propose a novel candidate biomarker complement component C9 which could add to current endoscopic surveillance strategy for early detection of adenocarcinoma.

scholarly journals Diagnostic value of research methods in diagnostics of chronic pancreatitis

2021 ◽  
Vol 102 (4) ◽  
pp. 528-536
Author(s):  
G R Aliyeva
Keyword(s):  
Chronic Pancreatitis ◽  
Early Stage ◽  
Imaging Modality ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Clinical History ◽  
Diagnostic Value ◽  
Diagnostic Tools ◽  
Invasive Approach ◽  
Pancreas Function ◽  
Function Testing

Chronic pancreatitis remains an unsolved problem for clinicians. One of the biggest dilemmas is to establish a clear diagnosis. Diagnosis can be particularly elusive in patients with early chronic pancreatitis. Many studies have been undertaken to improve diagnostics in chronic pancreatitis, but this has been significantly limited by the lack of a gold standard. The evaluation of patients with suspected chronic pancreatitis should follow a progressively non-invasive to more invasive approach. Computed tomography is the best primary imaging modality to obtain as it has good sensitivity for severe chronic pancreatitis and may exclude the need for other diagnostic tests. When ambiguous results are obtained, a magnetic resonance cholangiopancreatography may require for a more detailed evaluation of both the pancreatic parenchyma and ducts. If the diagnosis remains in doubt, endoscopic ultrasound with or without pancreas function testing becomes the preferred method. Endoscopic retrograde cholangiopancreatography remains a last line diagnostic test and generally should be used only for diagnostic purposes. Future researches in the field of diagnosis of early-stage chronic pancreatitis should purpose optimizing current diagnostic tools. A definitive diagnosis of chronic pancreatitis may not be made simply by clinical history, imaging or function testing alone, but rather by the data gathered by a combination of these diagnostic tools.

scholarly journals The Use of Eosinophil Count in Predicting the Need of Coronavirus Disease 2019 Patient for Treatment in Intensive Care Unit

2021 ◽  
Vol 9 (B) ◽  
pp. 631-635
Author(s):  
Ngakan Ketut Wira Suastika ◽  
Ketut Suega
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Eosinophil Count ◽  
Early Stage ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Receiver Operating Curve ◽  
Significant Difference ◽  
The Difference ◽  
Eosinophil Counts

BACKGROUND: Identification of coronavirus disease 2019 (COVID-19) patients who have the potential to become critical cases at an early stage and providing aggressive therapy can reduce the mortality rate. AIM: This study aims to determine the diagnostic value and differences of eosinophil counts in patients with COVID-19 who require treatment in intensive care unit (ICU) and non-ICU. METHOD: The prospective study was conducted on 382 patients with confirmed COVID-19 who were hospitalized from May to September 2020. Samples were obtained through consecutive sampling techniques. Mann–Whitney analysis was used to determine the difference of eosinophil counts in COVID-19 patients who require treatment in ICU and non-ICU. Receiver operating curve analysis was used to determine the diagnostic value of eosinophil count to predict the need of COVID-19 patients for treatment in ICU. RESULTS: There is a significant difference in the absolute and percentage eosinophil count in COVID-19 patients who need treatment in ICU and non-ICU. The area under the curve of absolute and percentage eosinophil count to predict the need of COVID-19 patients for treatment in ICU is 0.659 and 0.738, respectively. The best cutoff value, sensitivity and specificity of absolute and percentage eosinophil count is <0.025 × 103 μL and <0.25%; 77.7% and 78.3%; and 50.0% and 57.1%, respectively. CONCLUSIONS: The eosinophil count can be used as a biomarker to predict the need of COVID-19 patients for treatment in ICU.

scholarly journals Serum glycoprotein biomarker validation for esophageal adenocarcinoma and application to Barrett’s surveillance

2018 ◽  
Author(s):  
Alok K. Shah ◽  
Gunter Hartel ◽  
Ian Brown ◽  
Clay Winterford ◽  
Renhua Na ◽  
...  
Keyword(s):  
Barrett’S Esophagus ◽  
Esophageal Adenocarcinoma ◽  
Barrett's Esophagus ◽  
Binding Protein ◽  
Multiple Reaction Monitoring ◽  
Magnetic Bead ◽  
Low Grade ◽  
Complement Factor ◽  
Serum Glycoprotein ◽  
Serum Paraoxonase

SUMMARYBACKGROUND & AIMSEsophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett’s esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker panel for BE surveillance.METHODSSerum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS). The area under receiver operating characteristic curve was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multi-marker panel for BE surveillance.RESULTSDifferent glycoforms of complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarker candidates for EAC across both cohorts. A panel of 10 serum glycoproteins accurately discriminated BE patients not requiring intervention [BE+/-low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC]. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 glycoforms were increased with disease progression.CONCLUSIONSFurther prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted. A first-line BE surveillance blood test may be developed based on these findings.AbbreviationsAALAleuria aurantia lectin%CV% Co-efficient of variationAUROCArea under receiver operating characteristics curveBEBarrett’s esophagusBE-HGDBarrett’s esophagus with high-grade dysplasiaBE-IDBarrett’s esophagus which is indefinite for dysplasiaBE-LGDBarrett’s esophagus with low-grade dysplasiaBMIBody mass indexC1QBComplement C1q subcomponent subunit BC2Complement C2C3Complement C3C4BComplement C4-BC4BPAC4b-binding protein alpha chainC4BPBC4b-binding protein beta chainC9Complement component C9CFBComplement factor BCFIComplement factor ICIConfidence intervalCPCeruloplasminEACEsophageal adenocarcinomaEPHAErythroagglutinin from Phaseolus vulgarisFFPEFormalin-fixed, paraffin-embeddedGERDGastroesophageal reflux diseaseGSNGelsolinJACJacalin from Artocarpus integrifoliaLeMBALectin magnetic bead arrayMRM-MSMultiple reaction monitoring-mass spectrometryNPLNarcissus pseudonarcissus lectinNSENon-specialized epitheliumOROdds ratioPGLYRP2N-acetylmuramoyl-L-alanine amidasePON1Serum paraoxonase/arylesterase 1PON3Serum paraoxonase/lactonase 3RBP4Retinol-binding protein 4SERPINA4KallistatinSISStable isotope-labeled internal standard

scholarly journals Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ji Lyu ◽  
Lin Zhao ◽  
Fubo Wang ◽  
Jin Ji ◽  
Zhi Cao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Chinese Population ◽  
Prostate Volume ◽  
Early Stage ◽  
Diagnostic Value ◽  
Serum Markers ◽  
Diagnostic Tools ◽  
Serum Samples ◽  
Positive Rate ◽  
Serum Micrornas

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.

scholarly journals Impulse oscillometry for detection of small airway dysfunction in subjects with chronic respiratory symptoms and preserved pulmonary function

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Liang-Yuan Li ◽  
Tian-Sheng Yan ◽  
Jing Yang ◽  
Yu-Qi Li ◽  
Lin-Xi Fu ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Respiratory Symptoms ◽  
Early Stage ◽  
Roc Curves ◽  
Diagnostic Value ◽  
Small Airway ◽  
Impulse Oscillometry ◽  
Additional Method ◽  
Cutoff Values ◽  
Higher Sensitivity

Abstract Background Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF. Methods The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed. Results 209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5–R20 and Fres than those who didn’t. Subjects with dyspnea had higher R5, R5–R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5–R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5–R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002). Conclusion IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.

scholarly journals Diagnostic Value of Fluorescence Methods, Visual Inspection and Photographic Visual Examination in Initial Caries Lesion: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 9 (3) ◽  
pp. 30
Author(s):  
Mai Thi Giang Thanh ◽  
Ngo Van Toan ◽  
Do Thi Thanh Toan ◽  
Nguyen Phu Thang ◽  
Ngoc Quang Dong ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Assessment ◽  
Visual Inspection ◽  
Early Stage ◽  
Meta Analysis ◽  
Diagnostic Value ◽  
Caries Detection ◽  
Permanent Teeth ◽  
Visual Examination ◽  
Initial Caries

This systematic review and meta-analysis aimed to investigate the efficacy of fluorescence-based methods, visual inspections, and photographic visual examinations in initial caries detection. A literature search was undertaken in the PubMed and Cochrane databases. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed, and eligible articles published from 1 January 2009 to 30 October 2019 were included if they met the following criteria: they (1) assessed the accuracy of methods of detecting initial tooth caries lesions on occlusal, proximal, or smooth surfaces in both primary and permanent teeth (in clinical); (2) used a reference standard; (3) reported data regarding the sample size, prevalence of initial tooth caries, and accuracy of the methods. Data collection and extraction, quality assessment, and data analysis were conducted according to Cochrane standards Quality Assessment of Diagnostic Accuracy Studies-2. Statistical analyses were performed using Review Manager 5.3 and STATA 14.0. A total of 12 eligible articles were included in the meta-analysis. The results showed that the sensitivity and specificity of fluorescence-based methods were 80% and 80%, respectively; visual inspection was measured at 80% and 75%, respectively; photographic visual examination was measured at 67% and 79%, respectively. We found that the visual method and the fluorescence method were reliable for laboratory use to detect early-stage caries with equivalent accuracy.

scholarly journals Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1155
Author(s):  
Meihui Tian ◽  
Zhipeng Cao ◽  
Hao Pang
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Early Stage ◽  
Diagnostic Value ◽  
Circular Rnas ◽  
Cardiac Damage ◽  
Postmortem Diagnosis ◽  
Specific Expression ◽  
Forensic Practice ◽  
Artery Disease

The prevention and diagnosis of sudden cardiac death (SCD) are among the most important keystones and challenges in clinical and forensic practice. However, the diagnostic value of the current biomarkers remains unresolved issues. Therefore, novel diagnostic biomarkers are urgently required to identify patients with early-stage cardiovascular diseases (CVD), and to assist in the postmortem diagnosis of SCD cases without typical cardiac damage. An increasing number of studies show that circular RNAs (circRNAs) have stable expressions in myocardial tissue, and their time- and tissue-specific expression levels might reflect the pathophysiological status of the heart, which makes them potential CVD biomarkers. In this article, we briefly introduced the biogenesis and functional characteristics of circRNAs. Moreover, we described the roles of circRNAs in multiple SCD-related diseases, including coronary artery disease (CAD), myocardial ischemia or infarction, arrhythmia, cardiomyopathy, and myocarditis, and discussed the application prospects and challenges of circRNAs as a novel biomarker in the clinical and forensic diagnosis of SCD.

scholarly journals Morphologic Features of Cutaneous T-Cell Lymphomas Using Dermoscopy and High Frequency Ultrasound

2020 ◽  
Vol 10 (1) ◽  
pp. 17
Author(s):  
Iris Wohlmuth-Wieser ◽  
Joel M. Ramjist ◽  
Neil Shear ◽  
Raed Alhusayen
Keyword(s):  
T Cell ◽  
High Frequency ◽  
Early Stage ◽  
Skin Lesions ◽  
Diagnostic Tools ◽  
Skin Thickness ◽  
High Frequency Ultrasound ◽  
T Cell Lymphomas ◽  
Standardized Parameters ◽  
Frequency Ultrasound

The diagnosis of cutaneous T-cell lymphomas (CTCL) is frequently delayed by a median of three years and requires the clinical evaluation of an experienced dermatologist and a confirmatory skin biopsy. Dermoscopy and high-frequency ultrasound (HFUS) represent two non-invasive diagnostic tools. While dermoscopy is inexpensive and widely used for the diagnosis of melanoma and non-melanoma skin cancers, HFUS of skin lymphomas represents a novel diagnostic approach that is not yet implemented in the routine dermatologic practice. The aim of our study was to prospectively assess skin lesions of patients with either CTCL patches or plaques with dermoscopy and HFUS and to compare the findings with atopic dermatitis (AD) and psoriasis. Thirteen patients with an established diagnosis of CTCL, psoriasis, or AD were studied: Dermoscopy features including spermatozoa-like structures and the presence of white scales could assist in differentiating between early-stage CTCL and AD. HFUS measurements of the skin thickness indicated increased epidermal-, thickness in CTCL, and psoriasis compared with AD. Our results support the use of dermoscopy as a useful tool to diagnose CTCL. HFUS could augment the dermatologic assessment, but further studies will be needed to define standardized parameters.

scholarly journals Diagnostic work up of anemic patients: role of iron deficiency

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Daniela Meiser ◽  
Lale Kayikci ◽  
Matthias Orth
Keyword(s):  
Iron Deficiency ◽  
Complete Blood Count ◽  
Iron Status ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Diagnostic Tools ◽  
Operating Characteristics ◽  
Inflammatory Conditions ◽  
Reliable Parameter ◽  
Work Up

AbstractObjectivesDiagnosing disturbances in iron metabolism can be challenging when accompanied by inflammation. New diagnostic tools such as the “Thomas-plot” (TP) (relation of soluble transferrin receptor [sTfR]/log ferritin to reticulocyte hemoglobin content [RET-He]) were established to improve classification of anemias. Aim of this retrospective study was to assess the added diagnostic value of the TP in anemia work up.MethodsPatients from December 2016 to September 2018 with a complete blood count, iron status, RET-He and sTfR were manually classified into the four quadrants of the TP on basis of conventional iron markers. Manual and algorithm-based classifications were compared using cross tabulations, Box–Whisker-Plots as well as Receiver-Operating-Characteristics (ROC) to calculate the diagnostic accuracy using Area under the Curve (AUC) analysis.ResultsA total of 3,745 patients with a conventional iron status, including 1,721 TPs, could be evaluated. In 70% of the cases the manual classification was identical to the TP, in 10% it was deviant. 20% could not clearly be classified, mostly due to inflammatory conditions. In the absence of an inflammatory condition, ferritin was a reliable parameter to define iron deficiency (ID) (AUC 0.958). In the presence of inflammation, the significance of the ferritin index (AUC 0.917) and of the RET-He (AUC 0.957) increased.ConclusionsThe TP can be useful for narrowing down the causes of anemia in complex cases. Further studies with focus on special patient groups, e.g., oncological or rheumatic patients, are desirable.

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