scholarly journals Sensitivity and specificity of loss of heterozygosity analysis for the classification of rare germline variants in BRCA1/2: results of the observational AGO-TR1 study (NCT02222883)

2020 ◽  
pp. jmedgenet-2020-107353
Author(s):  
Jan Hauke ◽  
Philipp Harter ◽  
Corinna Ernst ◽  
Alexander Burges ◽  
Sandra Schmidt ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Sensitivity And Specificity ◽  
False Negative ◽  
High Sensitivity ◽  
High Specificity ◽  
Germline Variants ◽  
Variants Of Unknown Significance ◽  
Link Type ◽  
Registration Number ◽  
Low Sensitivity

Variant-specific loss of heterozygosity (LOH) analyses may be useful to classify BRCA1/2 germline variants of unknown significance (VUS). The sensitivity and specificity of this approach, however, remains unknown. We performed comparative next-generation sequencing analyses of the BRCA1/2 genes using blood-derived and tumour-derived DNA of 488 patients with ovarian cancer enrolled in the observational AGO-TR1 trial (NCT02222883). Overall, 94 pathogenic, 90 benign and 24 VUS were identified in the germline. A significantly increased variant fraction (VF) of a germline variant in the tumour indicates loss of the wild-type allele; a decreased VF indicates loss of the variant allele. We demonstrate that significantly increased VFs predict pathogenicity with high sensitivity (0.84, 95% CI 0.77 to 0.91), poor specificity (0.63, 95% CI 0.53 to 0.73) and poor positive predictive value (PPV; 0.71, 95% CI 0.62 to 0.79). Significantly decreased VFs predict benignity with low sensitivity (0.26, 95% CI 0.17 to 0.35), high specificity (1.0, 95% CI 0.96 to 1.00) and PPV (1.0, 95% CI 0.85 to 1.00). Variant classification based on significantly increased VFs results in an unacceptable proportion of false-positive results. A significantly decreased VF in the tumour may be exploited as a reliable predictor for benignity, with no false-negative result observed. When applying the latter approach, VUS identified in four patients can now be considered benign. Trial registration numberNCT02222883.

scholarly journals Role of endoscopy in suspicion of atrophic gastritis with and without intestinal metaplasia in comparison to histopathology

2021 ◽  
Vol 84 (1) ◽  
pp. 9-17
Author(s):  
H Ibrahim ◽  
A Shams El-Deen ◽  
ZA Kasemy ◽  
M Saad ◽  
AA Sakr
Keyword(s):  
Atrophic Gastritis ◽  
Intestinal Metaplasia ◽  
Sensitivity And Specificity ◽  
Chronic Gastritis ◽  
Gastrointestinal Symptoms ◽  
High Sensitivity ◽  
High Specificity ◽  
Poor Correlation ◽  
Gastric Lesions ◽  
Low Sensitivity

Background and study aims : Atrophic gastritis (AG) and intestinal metaplasia (IM) are established premalignant gastric lesions. Many studies documented a poor correlation between esophagogastroduodenoscopy (EGD) and histopathological (HP) findings of precancerous gastric lesions. The aim was to bridge the gap between endoscopy and HP in detection of chronic gastritis, AG and IM. Patients and methods : a prospective single-center study involved 150 patients with endoscopic criteria of gastric lesions with upper gastrointestinal symptoms referred for upper GI endoscopy met the endoscopic criteria and classified according to HP of biopsies from targeted gastric lesions into chronic gastritis (GI), AG(GII) or IM(GIII). We correlated the endoscopic criteria of the 3 groups with the HP results. Results : (73males & 75 females) with ages ranged17-75 years and mean± SD was 41.96 ± 15.95. GI, GII &GIII were [42 patients (28%),82 patients (54.7%) and 26 patients (17.3%)], respectively. Diffuse gastric mottling was more common in GI (74.3%, P<0.001), visible submucosal vessels, gastric atrophy predominated in GII (75.6, 82.3 & 73.1% (P 0.005,0.4 & <0.01)), respectively. Whitish raised lesions were more specific in GIII (85.7%) (P<0.001). The sensitivity and specificity of endoscopic suspicion of chronic gastritis were (86&88% in GI), (87&85% in GII) and (54% &100% in GIII) (p-0.001). The logistic regression model for risk factors was χ2= 25.74 and 49.32, p < 0.001. Conclusion : Conventional endoscopy has high sensitivity and specificity for suspicion of chronic gastritis and AG, but low sensitivity and very high specificity for IM. Targeted biopsies may be valuable with image enhanced techniques.

scholarly journals Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests

2021 ◽  
Author(s):  
J. J.J.M. Stohr ◽  
V. F. Zwart ◽  
G. Goderski ◽  
A. Meijer ◽  
C. R.S. Nagel-Imming ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
False Negative ◽  
Positive Culture ◽  
High Sensitivity ◽  
High Specificity ◽  
Antigen Detection ◽  
Qrt Pcr ◽  
Ct Value ◽  
Viral Culture ◽  
Self Testing

AbstractIntroductionSelf-testing for COVID-19 infection with lateral flow assay SARS-CoV-2 rapid antigen detection tests (RDT), provides rapid results and could enable frequent and extensive testing in the community, thereby improving the control of SARS-CoV-2. The objective of this study is to evaluate the performance of self-testing using RDT without assistance.MethodsParticipants visiting a municipal SARS-CoV-2 testing centre, received self-testing kits containing either the BD Veritor System (BD RDT) or Roche SARS-CoV-2 antigen detection test (Roche RDT). Oro-nasopharyngeal swabs were collected from the participants for qRT-PCR testing. As a proxy for contagiousness, viral culture was performed on a selection of qRT-PCR positive samples to determine the Ct-value at which the chance of a positive culture was dropping below 0.5 (Ct-value cut-off). Sensitivity and specificity of self-testing were compared to qRT-PCR with a Ct-value below the Ct value cut-off. Determinants independently associated with a false-negative self-test result were determined.ResultsA total of 3,215 participants were included (BD RDT n=1604; Roche RDT n=1611). Sensitivity and specificity of self-testing compared to the qRT-PCR results with Ct-value below the Ct-value cut-off was 78.0% (95% CI:72.5-82.8) and 99.4% (95%CI: 99.0-99.6) respectively. Determinants independently associated with a false-negative self-testing results were: higher age, low viral load and finding self-testing difficult.DiscussionSelf-testing using currently available RDT’s has a high specificity and relatively high sensitivity to identify individuals with a high probability of contagiousness. The performance of two tests were comparable. This application has the potential for frequent and extensive testing which may be an aid to lift restrictions to society while controlling the spread of SARS-CoV-2.

scholarly journals Evaluation of Recombinant Proteins of Burkholderia mallei for Serodiagnosis of Glanders

2012 ◽  
Vol 19 (8) ◽  
pp. 1193-1198 ◽  
Author(s):  
Vijai Pal ◽  
Subodh Kumar ◽  
Praveen Malik ◽  
Ganga Prasad Rai
Keyword(s):  
Sensitivity And Specificity ◽  
Recombinant Proteins ◽  
False Negative ◽  
Enzyme Linked Immunosorbent Assay ◽  
Burkholderia Mallei ◽  
Content Type ◽  
Whole Cells ◽  
Negative Results ◽  
Elisa Format ◽  
Low Sensitivity

ABSTRACTGlanders is a contagious disease caused by the Gram-negative bacillusBurkholderia mallei. The number of equine glanders outbreaks has increased steadily during the last decade. The disease must be reported to the Office International des Epizooties, Paris, France. Glanders serodiagnosis is hampered by the considerable number of false positives and negatives of the internationally prescribed tests. The major problem leading to the low sensitivity and specificity of the complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) has been linked to the test antigens currently used, i.e., crude preparations of whole cells. False-positive results obtained from other diagnostic tests utilizing crude antigens lead to financial losses to animal owners, and false-negative results can turn a risk into a possible threat. In this study, we report on the identification of diagnostic targets using bioinformatics tools for serodiagnosis of glanders. The identified gene sequences were cloned and expressed as recombinant proteins. The purified recombinant proteins ofB. malleiwere used in an indirect ELISA format for serodiagnosis of glanders. Two recombinant proteins, 0375H and 0375TH, exhibited 100% sensitivity and specificity for glanders diagnosis. The proteins also did not cross-react with sera from patients with the closely related disease melioidosis. The results of this investigation highlight the potential of recombinant 0375H and 0375TH proteins in specific and sensitive diagnosis of glanders.

Is Endoscopic Assessment of the Esophagus and Stomach Enough to Determine the Need for Biopsy at These Sites in Pediatric Patients Undergoing Endoscopy for Elevated TTG?

2021 ◽  
pp. 109352662199148
Author(s):  
M. Cristina Pacheco ◽  
Nicole Green ◽  
Jane Dickerson ◽  
Dale Lee
Keyword(s):  
Sensitivity And Specificity ◽  
Pediatric Patients ◽  
Tissue Transglutaminase ◽  
Immunoglobulin A ◽  
High Specificity ◽  
Visual Assessment ◽  
Pathology Report ◽  
Low Sensitivity ◽  
Endoscopic Assessment

Objectives The goal of our study was to determine whether visual assessment of the esophagus and stomach could predict abnormal histology and determine the frequency of interventions based on biopsies in patients undergoing endoscopy for elevated tissue transglutaminase immunoglobulin A antibody (TTG). Methods Pathology records were searched for patients with biopsy performed for elevated TTG. Pathology report, endoscopy report, and follow-up were obtained and slides from the duodenum reviewed. Pathology was considered gold standard for sensitivity and specificity calculations. Results 240 patients were included. 215 patients had esophageal biopsies performed. Esophageal endoscopic visual assessment had sensitivity of 47% and specificity of 93% for abnormal histology. 16(7%) patients had therapy or referral related to results and, of these, 6(38%) had visually normal endoscopy. 237 biopsies were performed of stomach. Gastric endoscopic visual assessment had a sensitivity and specificity of 20% and 87%. 24(10%) patients had therapy based on findings and, of these, 12 (50%) had visually normal endoscopy. Conclusions Endoscopic assessment of esophagus and stomach has low sensitivity and high specificity for pathologic abnormalities when indication for endoscopy is elevated TTG. When endoscopy is visually normal clinical interventions based on biopsy are rare, and foregoing biopsy may be considered.

scholarly journals Correlation of Immunohistochemistry and Fluorescence in Situ Hybridization for HER-2 Assessment in Breast Cancer Patients: Single Centre Experience

2018 ◽  
Vol 6 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Magdalena Bogdanovska-Todorovska ◽  
Slavica Kostadinova-Kunovska ◽  
Rubens Jovanovik ◽  
Blagica Krsteska ◽  
Goran Kondov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
In Situ Hybridisation ◽  
False Negative ◽  
High Sensitivity ◽  
High Specificity ◽  
Fluorescence In Situ Hybridisation ◽  
Breast Cancer Patients ◽  
Her 2

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.

Pearls and Pitfalls of Interpretation in CT Colonography

2020 ◽  
Vol 71 (2) ◽  
pp. 140-148
Author(s):  
Michael Schonberger ◽  
Philippe Lefere ◽  
Abraham H. Dachman
Keyword(s):  
Computed Tomography ◽  
Sensitivity And Specificity ◽  
False Positive ◽  
Ct Colonography ◽  
False Negative ◽  
High Sensitivity ◽  
Negative Results ◽  
False Negative Results ◽  
The Common

The accuracy of computed tomography (CT) colonography (CTC) requires that the radiologist be well trained in the recognition of pitfalls of interpretation. In order to achieve a high sensitivity and specificity, the interpreting radiologist must be well versed in the causes of both false-positive and false-negative results. In this article, we review the common and uncommon pitfalls of interpretation in CTC.

scholarly journals Is high-sensitivity troponin, alone or in combination with copeptin, sensitive enough for ruling out NSTEMI in very early presenters at admission? A post hoc analysis performed in emergency departments

BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e023994 ◽  
Author(s):  
Camille Chenevier-Gobeaux ◽  
Mustapha Sebbane ◽  
Christophe Meune ◽  
Sophie Lefebvre ◽  
Anne-Marie Dupuy ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
False Negative ◽  
High Sensitivity ◽  
Threshold Value ◽  
St Segment Elevation ◽  
Post Hoc Analysis ◽  
Registration Number ◽  
Post Hoc

ObjectivesCopeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters.SettingWe performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours.Participants449 patients were included, in whom 12% had NSTEMI. CPO occurred <2 hours from ED presentation in 160, between 2 and 4 hours in 143 and >4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281).MeasuresDiagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured.ResultsDiagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO <2 hours, the choice of a threshold value of 14 ng/L for HS-cTnT resulted in three false negative (Sensitivity 80%(95% CI 51% to 95%); specificity 85% (95% CI 78% to 90%); 79% of correctly ruled out patients) and that of 5 ng/L in two false negative (sensitivity 87% (95% CI 59% to 98%); specificity 58% (95% CI 50% to 66%); 52% of correctly ruled out patients). The addition of copeptin to HS-cTnT induced a decrease of misclassified patients to 1 in patients with CPO <2 hours (sensitivity 93% (95% CI 66% to 100%); specificity 41% (95% CI 33% to 50%)).ConclusionA single measurement of HS-cTn, alone or in combination with copeptin at admission, seems not safe enough for ruling out NSTEMI in very early presenters (with CPO <2 hours).Trial registration numberDC-2009–1052

Epstein-Barr Virus (EBV)-Encoded RNA: Automated In-Situ Hybridization (ISH) Compared with Manual ISH and Immunohistochemistry for Detection of EBV in Pediatric Lymphoproliferative Disorders

2009 ◽  
Vol 12 (3) ◽  
pp. 195-199 ◽  
Author(s):  
Naim K. Fanaian ◽  
Cynthia Cohen ◽  
Sandra Waldrop ◽  
Jennifer Wang ◽  
Bahig M. Shehata
Keyword(s):  
In Situ Hybridization ◽  
Predictive Value ◽  
Epstein Barr Virus ◽  
High Sensitivity ◽  
High Specificity ◽  
Lymphoproliferative Disorders ◽  
Barr Virus ◽  
Epstein Barr ◽  
Low Sensitivity

Detection of Epstein-Barr virus (EBV) may be achieved by various methods, including EBV-encoded RNA (EBER) in-situ hybridization (ISH) and immunohistochemistry (IHC) for latent membrane protein (LMP-1). We compared novel automated ISH and IHC techniques in pediatric lymphoproliferative disorders with results obtained by manual ISH. Thirty-seven pediatric cases previously studied by manual EBER ISH (including 18 EBER-positive, 15 EBER-negative, and 4 EBER-equivocal cases) were used for the study. Automated EBER ISH and automated LMP-1 IHC were performed using the BondMax autostainer and prediluted EBER probe and EBV cell surface 1 to 4 at 1:50 dilution, respectively. Results of each of the automated techniques for EBV detection were compared with results by manual EBER ISH. Compared with manual EBER ISH as the gold standard, automated ISH had a sensitivity and specificity of 94% and 69%, respectively, accuracy of 83%, positive predictive value (PPV) of 79%, and negative predictive value (NPV) of 90%. Automated IHC had a sensitivity of 44%, specificity of 93%, accuracy of 67%, PPV of 88%, and NPV of 59%. Automated ISH and IHC correlated significantly ( P < 0.045). Automated ISH is useful for diagnosis of EBV-related pediatric neoplasms, being easy to perform and interpret and requiring only the technologist's time to set up and having a high sensitivity and NPV. The automated IHC protocol is of too low sensitivity for routine use, although results show high specificity and PPV.

scholarly journals Diagnosis of prion diseases by RT-QuIC results in improved surveillance

Neurology ◽  
2020 ◽  
Vol 95 (8) ◽  
pp. e1017-e1026 ◽  
Author(s):  
Daniel D. Rhoads ◽  
Aleksandra Wrona ◽  
Aaron Foutz ◽  
Janis Blevins ◽  
Kathleen Glisic ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
Prion Disease ◽  
Disease Surveillance ◽  
Prion Diseases ◽  
False Negative ◽  
High Sensitivity ◽  
Disease Type ◽  
Diagnostic Sensitivity ◽  
Class Iii ◽  
The Impact

ObjectiveTo present the National Prion Disease Pathology Surveillance Center's (NPDPSC’s) experience using CSF real-time quaking-induced conversion (RT-QuIC) as a diagnostic test, to examine factors associated with false-negative RT-QuIC results, and to investigate the impact of RT-QuICs on prion disease surveillance.MethodsBetween May 2015 and April 2018, the NPDPSC received 10,498 CSF specimens that were included in the study. Sensitivity and specificity analyses were performed on 567 autopsy-verified cases. Prion disease type, demographic characteristics, specimen color, and time variables were examined for association with RT-QuIC results. The effect of including positive RT-QuIC cases in prion disease surveillance was examined.ResultsThe diagnostic sensitivity and specificity of RT-QuIC across all prion diseases were 90.3% and 98.5%, respectively. Diagnostic sensitivity was lower for fatal familial insomnia, Gerstmann-Sträussler-Scheinker disease, sporadic fatal insomnia, variably protease sensitive prionopathy, and the VV1 and MM2 subtypes of sporadic Creutzfeldt-Jakob disease. Individuals with prion disease and negative RT-QuIC results were younger and had lower tau levels and nonelevated 14-3-3 levels compared to RT-QuIC–positive cases. Sensitivity was high throughout the disease course. Some cases that initially tested RT-QuIC negative had a subsequent specimen test positive. Including positive RT-QuIC cases in surveillance statistics increased laboratory-based case ascertainment of prion disease by 90% over autopsy alone.ConclusionsRT-QuIC has high sensitivity and specificity for diagnosing prion diseases. Sensitivity limitations are associated with prion disease type, age, and related CSF diagnostic results. RT-QuIC greatly improves laboratory-based prion disease ascertainment for surveillance purposes.Classification of evidenceThis study provides Class III evidence that second-generation RT-QuIC identifies prion disease with a sensitivity of 90.3% and specificity of 98.5% among patients being screened for these diseases due to concerning symptoms.

scholarly journals Validation of the French version of the McLean Screening Instrument for Adolescent Borderline Personality Disorder (MSI-BPD)

2020 ◽  
Author(s):  
Bojan Mirkovic ◽  
Mario Speranza ◽  
Lionel Cailhol ◽  
Julien-Daniel Guelfi ◽  
Fernando Perez-Diaz ◽  
...  
Keyword(s):  
Borderline Personality Disorder ◽  
Personality Disorder ◽  
Psychometric Properties ◽  
High Sensitivity ◽  
High Specificity ◽  
Structured Interview ◽  
Screening Instrument ◽  
Borderline Personality ◽  
French Version ◽  
Low Sensitivity

Abstract Background: The study examines the psychometric properties of the French version of the McLean Screening Instrument for Borderline Personality Disorder (MSI-BPD) created by M. Zanarini to screen borderline personality disorder in clinical and non-clinical populations.Method: In this multicentric longitudinal study from the European Network on Borderline Personality Disorder, a sample of 84 adolescent patients from five psychiatric centres and 85 matched controls without psychiatric comorbidity completed the MSI-BPD, French version, and were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV), in order to assess the presence or absence of borderline personality disorder.Results: The MSI-BPD showed excellent internal consistency (α = 0.87 [0.84;0.90]). Compared to the semi-structured reference interview (SIDP-IV), the MSI-BPD showed substantial congruent validity (AUC = 0.93, CI 95%: 0.90 - 0.97). The optimal cut-off point in the present study was 5 or more, as it had relatively high sensitivity (0.87) and specificity (0.85). In our sample, the cut-off point (7 or more) proposed by the original developers of the MSI-BPD showed high specificity (0.95) but low sensitivity (0.63).Conclusions: The French version of the MSI-BPD is now available, and its psychometric properties are satisfactory. The French version of the MSI-PBD can be used as a screening tool for borderline personality disorder, for clinical purposes or in research studies.

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