Detection of antineutrophil cytoplasmic antibodies (ANCAs): a multicentre European Vasculitis Study Group (EUVAS) evaluation of the value of indirect immunofluorescence (IIF) versus antigen-specific immunoassays

ObjectiveThis multicentre study was performed to evaluate the diagnostic accuracy of a wide spectrum of novel technologies nowadays available for detection of myeloperoxidase (MPO) and proteinase 3 (PR3)-antineutrophil cytoplasmic antibodies (ANCAs).MethodsSera (obtained at the time of diagnosis) from 251 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 924 disease controls were tested for the presence of cytoplasmic pattern/perinuclear pattern and atypical ANCA (A-ANCA) by indirect immunofluorescence (IIF) (at two sites) and for the presence of PR3-ANCA and MPO-ANCA by eight different immunoassays.ResultsThe area under the curve (AUC) of the receiver operating characteristic curve to discriminate AAV from controls was 0.923 (95% CI 0.902 to 0.944) and 0.843 (95% CI 0.814 to 0.871) for the two IIF methods. For the antigen-specific immunoassays, the AUC varied between 0.936 (95% CI 0.912 to 0.960) and 0.959 (95% CI 0.941 to 0.976), except for one immunoassay for which the AUC was 0.919 (95% CI 0.892 to 0.945).ConclusionsOur comparison of various ANCA detection methods showed (i) large variability between the two IIF methods tested and (ii) a high diagnostic performance of PR3-ANCA and MPO-ANCA by immunoassay to discriminate AAV from disease controls. Consequently, dual IIF/antigen-specific immunoassay testing of each sample is not necessary for maximal diagnostic accuracy. These results indicate that the current international consensus on ANCA testing for AAV needs revision.

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Value of Fibrinogen to Discriminate Appendicitis from Nonspecific Abdominal Pain in Preschool Children

European Journal of Pediatric Surgery ◽

10.1055/s-0039-1692166 ◽

2019 ◽

Vol 30 (04) ◽

pp. 357-363

Author(s):

Javier Gómez-Veiras ◽

Ángel Salgado-Barreira ◽

José Luis Vázquez ◽

Margarita Montero-Sánchez ◽

José Ramón Fernández-Lorenzo ◽

...

Keyword(s):

Abdominal Pain ◽

Preschool Children ◽

Diagnostic Accuracy ◽

Prothrombin Time ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Value ◽

Suspected Appendicitis ◽

Uncomplicated Appendicitis ◽

Good Diagnostic Accuracy

Introduction The aim of this study was to assess the diagnostic value of the biomarker fibrinogen (FB), along with the markers white blood cell (WBC) count, absolute neutrophil count (ANC), and C-reactive protein (CRP), to discriminate appendicitis from nonspecific abdominal pain (NSAP) in preschool children. Materials and Methods We prospectively evaluated all children aged <5 years admitted for suspected appendicitis at an academic pediatric emergency department during 5 years. Diagnostic accuracy of FB (prothrombin time–derived method), WBC, ANC, and CRP were assessed by the area under the curve (AUC) of the receiver-operating characteristic curve. Results A total of 82 patients were enrolled in the study (27 NSAP, 17 uncomplicated, and 38 complicated appendicitides). WBC and ANC had moderate diagnostic accuracy for appendicitis versus NSAP (WBC: AUC 0.66, ANC: AUC 0.67). CRP and FB had good diagnostic accuracy for appendicitis versus NSAP (CRP: AUC 0.78, FB: AUC 0.77). WBC and ANC are not useful to discriminate complicated versus uncomplicated appendicitis (WBC: AUC 0.43, ANC: AUC 0.45). CPR and FB had good diagnostic accuracy for complicated versus uncomplicated appendicitis (CRP: AUC 0.80, FB: AUC 0.73). Conclusion CRP and FB are more useful than WBC and ANC to discriminate appendicitis from NSAP in preschool children. CRP and FB are especially useful to discriminate complicated from uncomplicated appendicitis and NSAP. In a child with suspected appendicitis, a plasma FB level (prothrombin time–derived method) >540 mg/dL is associated with an increased likelihood of complicated appendicitis.

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Diagnostic accuracy of IGF-1 for screening growth hormone deficiency: a prospective, single-center, diagnostic accuracy study

10.21203/rs.3.rs-430014/v1 ◽

2021 ◽

Author(s):

Hideyuki Iwayama ◽

Sachiko Kitagawa ◽

Jyun Sada ◽

Ryosuke Miyamoto ◽

Tomohito Hayakawa ◽

...

Keyword(s):

Growth Hormone ◽

Diagnostic Accuracy ◽

Growth Hormone Deficiency ◽

Predictive Value ◽

Screening Test ◽

Characteristic Curve ◽

Area Under The Curve ◽

Rank Correlation ◽

Hormone Deficiency ◽

Height Velocity

Abstract Purpose We evaluated the diagnostic accuracy of insulin-like growth factor-1 (IGF-1) for screening growth hormone deficiency (GHD) to determine the usefulness of IGF-1 as a screening test. Methods On 298 consecutive children who had short stature or decreased height velocity, we measured IGF-1 levels and performed growth hormone (GH) secretion test using clonidine, arginine, and, in cases with different results of the two tests, L-dopa. Patients with congenital abnormalities were excluded. GHD was defined as peak GH ≤ 6.0 ng/mL in the two tests. Results We identified 60 and 238 patients with and without GHD, respectively. The mean IGF-1 (SD) was not significantly different between the GHD and non-GHD groups (p = 0.23). Receiver operating characteristic curve analysis demonstrated the best diagnostic accuracy at an IGF-1 cutoff of −1.493 SD, with sensitivity of 0.685, specificity of 0.417, positive predictive value of 0.25, negative predictive value of 0.823, and area under the curve of 0.517. Spearman’s rank correlation coefficient showed that IGF-1 (SD) was weakly correlated with age, bone age, height velocity before examination, weight (SD), and BMI (SD) and very weakly correlated with height (SD), target height (SD), and maximum GH peak. Conclusion IGF-1 level had poor diagnostic accuracy as a screening test for GHD. Correlation analysis revealed that none of the items increased the diagnostic power of IGF-1. Therefore, IGF-1 should not be used alone in the screening of GHD. A predictive biomarker for GHD should be developed in the future.

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Combined 18F-FET PET and diffusion kurtosis MRI in post-treatment glioblastoma: differentiation of true progression from treatment related changes

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab044 ◽

2021 ◽

Author(s):

Francesco D’Amore ◽

Farida Grinberg ◽

Jörg Mauler ◽

Norbert Galldiks ◽

Ganna Blazhenets ◽

...

Keyword(s):

Logistic Regression ◽

Diagnostic Accuracy ◽

Diffusion Mri ◽

Tumour Progression ◽

Characteristic Curve ◽

Area Under The Curve ◽

Regions Of Interest ◽

Fet Pet ◽

Diffusion Kurtosis ◽

And Diffusion

Abstract Background Radiological differentiation of tumour progression (TPR) from treatment-related changes (TRC) in pre-treated glioblastoma is crucial. This study aimed to explore the diagnostic value of diffusion kurtosis MRI combined with information derived from O-(2-[ 18F]-fluoroethyl)-L-tyrosine ( 18F-FET) PET for the differentiation of TPR from TRC in patients with pre-treated glioblastoma. Methods Thirty-two patients with histomolecularly defined and pre-treated glioblastoma suspected of having TPR were included in this retrospective study. Twenty-one patients were included in the TPR group, and 11 patients in the TRC group, as assessed by neuropathology or clinicoradiological follow-up. 3D regions-of-interest were generated based on increased 18F-FET uptake using a brain-to-tumour ratio of 1.6. Furthermore, diffusion MRI kurtosis maps were obtained from the same regions-of-interests using co-registered 18F-FET PET images, and an advanced histogram analysis of diffusion kurtosis map parameters was applied to generated 3D regions-of-interest. Diagnostic accuracy was analysed by receiver-operating characteristic curve analysis and combinations of PET and MRI parameters using multivariate logistic regression. Results Parameters derived from diffusion MRI kurtosis maps show high diagnostic accuracy, up to 88%, for differentiating between TPR and TRC. Logistic regression revealed that the highest diagnostic accuracy of 94% (area under the curve, 0.97; sensitivity, 94%; specificity, 91%) was achieved by combining the maximum tumour-to-brain ratio of 18F-FET uptake and diffusion MRI kurtosis metrics. Conclusions The combined use of 18F-FET PET and MRI diffusion kurtosis maps appears to be a promising approach to improve the differentiation of TPR from TRC in pre-treated glioblastoma and warrants further investigation.

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Reliability of Using the Proposed International Consensus Video Signs of Potential Concussion for National Rugby League Head Impact Events

Neurosurgery ◽

10.1093/neuros/nyaa437 ◽

2020 ◽

Author(s):

Andrew J Gardner

Keyword(s):

Characteristic Curve ◽

Area Under The Curve ◽

Rugby League ◽

Head Impact ◽

International Consensus ◽

Global Consistency ◽

Definition Of ◽

Sensitivity Specificity ◽

Individual Sports ◽

Impact Events

Abstract BACKGROUND Consensus on the definition of extant video signs of concussion have recently been proposed by representatives of international sporting codes for global consistency across professional leagues. OBJECTIVE To review the reliability of the proposed international consensus video signs of concussion in National Rugby League (NRL) head impact events (HIEs). METHODS The video signs of concussion were coded for every HIE during the 2019 NRL season. Coding was conducted blinded to the concussion status. Frequency, sensitivity, specificity, and a receiver operating characteristic curve were calculated. RESULTS There were 943 HIEs identified over the 2019 NRL season, of which 106 resulted in a diagnosed concussion. The most frequently observed video sign in concussed athletes was blank/vacant look (54%), which was also the most sensitive video sign (0.54, CI: 0.44-0.63), while the most specific was tonic posturing (0.99, CI: 0.99-1.00). In 43.4% of diagnosed concussions none of the 6 video signs were present. The 6 video signs demonstrated a “fair” ability to discriminate between concussion and nonconcussion HIEs (area under the curve = 0.76). CONCLUSION International consensus agreement between collision sports for extant video signs of concussion and the definition of those extant video signs are clinically important. The selection of signs requires rigorous assessment to examine their predictive value across all sports and within individual sports, and to determine further video signs to compliment and improve the identification of possible concussion events within various sports. The current study demonstrated that, for NRL-related HIEs, the diagnostic accuracy of video signs varies.

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Evaluation of PR3- and MPO-ANCA line and dot immunoassays in ANCA-associated vasculitis

Rheumatology ◽

10.1093/rheumatology/keaa776 ◽

2020 ◽

Author(s):

Nina Kempiners ◽

Juliane Mahrhold ◽

Bernhard Hellmich ◽

Elena Csernok

Keyword(s):

Operating Characteristic ◽

Characteristic Curve ◽

Area Under The Curve ◽

Test Method ◽

Detection Methods ◽

First Line ◽

Anca Associated Vasculitis ◽

Line Test ◽

High Degree ◽

Better Than

Abstract Objective This study was performed to evaluate the diagnostic accuracy of novel line and dot immunoassays for detection of MPO and PR3 ANCA. Methods Sera from 50 patients with ANCA-associated vasculitis (AAV), including granulomatosis with polyangiitis and microscopic polyangiitis, and from 45 disease controls were tested by IIF and for the presence of PR3-ANCA and MPO-ANCA by four different line or dot immunoassays, as well as by a chemiluminescence immunoassay. Results The area under the curve of the receiver operating characteristic curve to discriminate AAV from controls was 0.858 (95% CI 0.785–0.931) for the IIF method. For the antigen-specific immunoassays, the area under the curve varied between 0.869 (95% CI 0.797–0.941) and 0.936 (95% 0.886–0.985). Conclusions Our comparison of various ANCA detection methods showed a high degree of diagnostic precision for all of the PR3- and MPO-ANCA line and dot immunoassays investigated. The performance was equal to or better than the performance of IIF. These results indicate that novel line and dot immunoassays can serve as a first-line test method in patients with the suspected diagnosis of AAV.

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Methylation of IGF2 regulatory regions to diagnose adrenocortical carcinomas

Endocrine Related Cancer ◽

10.1530/erc-16-0266 ◽

2016 ◽

Vol 23 (9) ◽

pp. 727-737 ◽

Cited By ~ 13

Author(s):

S G Creemers ◽

P M van Koetsveld ◽

F J van Kemenade ◽

T G Papathomas ◽

G J H Franssen ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Area Under The Curve ◽

Regulatory Regions ◽

Large Variability ◽

Real Time Quantitative Pcr ◽

Adrenocortical Adenomas ◽

Rare Malignancy ◽

Adrenocortical Carcinomas ◽

Methylation Patterns ◽

Independent Cohort

Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Discrimination of ACCs from adrenocortical adenomas (ACAs) is challenging on both imaging and histopathological grounds. High IGF2 expression is associated with malignancy, but shows large variability. In this study, we investigate whether specific methylation patterns of IGF2 regulatory regions could serve as a valuable biomarker in distinguishing ACCs from ACAs. Pyrosequencing was used to analyse methylation percentages in DMR0, DMR2, imprinting control region (ICR) (consisting of CTCF3 and CTCF6) and the H19 promoter. Expression of IGF2 and H19 mRNA was assessed by real-time quantitative PCR. Analyses were performed in 24 ACCs, 14 ACAs and 11 normal adrenals. Using receiver operating characteristic (ROC) analysis, we evaluated which regions showed the best predictive value for diagnosis of ACC and determined the diagnostic accuracy of these regions. In ACCs, the DMR0, CTCF3, CTCF6 and the H19 promoter were positively correlated with IGF2 mRNA expression (P<0.05). Methylation in the most discriminating regions distinguished ACCs from ACAs with a sensitivity of 96%, specificity of 100% and an area under the curve (AUC) of 0.997±0.005. Our findings were validated in an independent cohort of 9 ACCs and 13 ACAs, resulting in a sensitivity of 89% and a specificity of 92%. Thus, methylation patterns of IGF2 regulatory regions can discriminate ACCs from ACAs with high diagnostic accuracy. This proposed test may become the first objective diagnostic tool to assess malignancy in adrenal tumours and facilitate the choice of therapeutic strategies in this group of patients.

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Antineutrophil Cytoplasmic Antibodies Testing in a Large Cohort of Unselected Greek Patients

Autoimmune Diseases ◽

10.4061/2011/626495 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Konstantinos Tsiveriotis ◽

Alexandra Tsirogianni ◽

Elena Pipi ◽

Konstantinos Soufleros ◽

Chryssa Papasteriades

Keyword(s):

Connective Tissue ◽

Diagnostic Accuracy ◽

Indirect Immunofluorescence ◽

Large Cohort ◽

Antineutrophil Cytoplasmic Antibodies ◽

Gastrointestinal Disorders ◽

Connective Tissue Disorders ◽

Serum Samples ◽

Low Prevalence ◽

Positive Results

Objective. To retrospectively evaluate ANCA testing in a cohort of unselected Greek in- and outpatients.Methods. In 10803 consecutive serum samples, ANCA were tested by indirect immunofluorescence (IIF) and ELISA. ELISA in inpatients was performed only on IIF positive sera.Results. Low prevalence (6.0%) of IIF positive samples was observed. Among these samples, 63.5% presented perinuclear (p-ANCA), 9.3% cytoplasmic (c-ANCA) and 27.2% atypical (x-ANCA) pattern. 16.1% of p-ANCA were antimyeloperoxidase (anti-MPO) positive, whereas 68.3% of c-ANCA were antiproteinase-3 (anti-PR3) positive. Only 17 IIF negative outpatients' samples were ELISA positive. ANCA-associated vasculitides (AAV), connective tissue disorders and gastrointestinal disorders represented 20.5%, 23.9%, and 21.2% of positive results, respectively. AAV patients exhibited higher rates of MPO/PR3 specificity compared to non-AAV (93.8% versus 8%).Conclusions. This first paper on Greek patients supports that screening for ANCA by IIF and confirming positive results by ELISA minimize laboratory charges without sacrificing diagnostic accuracy.

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Urinary Cell-Free miR-99a-5p as a Potential Biomarker for Estrus Detection in Buffalo

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.643910 ◽

2021 ◽

Vol 8 ◽

Author(s):

Aparna Hebbar ◽

Rajeev Chandel ◽

Payal Rani ◽

Suneel Kumar Onteru ◽

Dheer Singh

Keyword(s):

Characteristic Curve ◽

Area Under The Curve ◽

High Sensitivity ◽

Detection Methods ◽

Non Invasive ◽

Discovery Sample ◽

Potential Biomarker ◽

Estrus Detection ◽

Buffalo Urine

Accurate estrus detection method is the need of the hour to improve reproductive efficiency of buffaloes in dairy industry, as the currently available estrus detection methods/tools lack high sensitivity and specificity. Recently, circulating miRNAs have been shown as non-invasive biomarkers by various studies. Hence, in order to evaluate their potential as estrus biomarkers, the objective of this study was to identify and compare the levels of 10 hormone-responsive miRNAs in the urine collected at proestrus (PE), estrus (E), and diestrus (DE) phases of buffaloes (n = 3) pertaining to a discovery sample. Among 10 urinary miRNAs, the levels of bta-mir-99a-5p (E/PE 0.5-fold, P < 0.05; DE/PE 1.9-fold), bta-miR-125b (E/PE 0.5-fold; DE/PE 0.7-fold), bta-mir-145 (E/PE 1.5-fold; DE/PE 0.7-fold), bta-mir-210 (E/PE 1.2-fold, DE/PE 0.7-fold), mir-21 (E/PE 1.5-fold, DE/PE 2-fold), and bta-mir-191 (E/PE 1.3-fold; DE/PE 0.8-fold) were found to be altered during different phases of buffalo estrous cycle. In contrast, bta-mir-126-3p, bta-let-7f, bta-mir-16b, and bta-mir-378 were undetected in buffalo urine. Furthermore, a validation study in an independent group of 25 buffalo heifers showed the increased levels of urinary bta-mir-99a-5p during the DE (3.92-fold; P < 0.0001) phase as compared to the E phase. Receiver operating characteristic curve analyses also revealed the ability of urinary miR-99a-5p in distinguishing the E from the DE phase (area under the curve of 0.6464; P < 0.08). In silico analysis further showed an enrichment of miR-99a-5p putative targets in various ovarian signaling pathways, including androgen/estrogen/progesterone biosynthesis and apoptosis signaling, implicating the role of miR-99a-5p in ovarian physiology. In conclusion, significantly lower levels of bta-mir-99a-5p at the E phase than the DE phase in buffalo urine indicate its biomarker potential, which needs to be further explored in a large cohort in the future studies.

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Diagnostic Accuracy of Noncontrast CT in Detecting Acute Appendicitis: A Meta-analysis of Prospective Studies

The American Surgeon ◽

10.1177/000313481508100629 ◽

2015 ◽

Vol 81 (6) ◽

pp. 626-629 ◽

Cited By ~ 11

Author(s):

Bing Xiong ◽

Baishu Zhong ◽

Zhenwei Li ◽

Feng Zhou ◽

Ruying Hu ◽

...

Keyword(s):

Acute Appendicitis ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Meta Analysis ◽

Characteristic Curve ◽

Area Under The Curve ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Summary Receiver Operating Characteristic ◽

Noncontrast Ct

The aim of the study is to evaluate the diagnostic accuracy of noncontrast CT in detecting acute appendicitis. Prospective studies in which noncontrast CT was performed to evaluate acute appendicitis were found on PubMed, EMBASE, and Cochrane Library. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were assessed. The summary receiver-operating characteristic curve was conducted and the area under the curve was calculated. Seven original studies investigating a total of 845 patients were included in this meta-analysis. The pooled sensitivity and specificity were 0.90 (95% CI: 0.86–0.92) and 0.94 (95% CI: 0.92–0.97), respectively. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio was 12.90 (95% CI: 4.80–34.67), 0.09 (95% CI: 0.04–0.20), and 162.76 (95% CI: 31.05–853.26), respectively. The summary receiver-operating characteristic curve was symmetrical and the area under the curve was 0.97 (95% CI: 0.95–0.99). In conclusion, noncontrast CT has high diagnostic accuracy in detecting acute appendicitis, which is adequate for clinical decision making.

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Blood Procalcitonin Level as A Diagnostic Marker of Pediatric Bacterial Meningitis: A Systematic Review and Meta-Analysis

Diagnostics ◽

10.3390/diagnostics11050846 ◽

2021 ◽

Vol 11 (5) ◽

pp. 846

Author(s):

Heeyeon Kim ◽

Yun-Ho Roh ◽

Seo-Hee Yoon

Keyword(s):

Bacterial Meningitis ◽

Diagnostic Accuracy ◽

Meta Analysis ◽

Characteristic Curve ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Summary Receiver Operating Characteristic ◽

Mortality And Morbidity ◽

Meningitis In Children ◽

Sensitivity Specificity

Early diagnosis and treatment of bacterial meningitis in children are essential, due to the high mortality and morbidity rates. However, lumbar puncture is often difficult, and cerebrospinal fluid (CSF) culture takes time. This meta-analysis aims to determine the diagnostic accuracy of blood procalcitonin for detecting bacterial meningitis in children. We conducted a systematic search on electronic databases to identify relevant studies. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated, and a hierarchical summary receiver operating characteristic curve and area under the curve (AUC) were determined. Eighteen studies with 1462 children were included in the analysis. The pooled sensitivity, specificity, and the DOR of blood procalcitonin for detecting bacterial meningitis were 0.87 (95% confidence interval (CI): 0.78–0.93); 0.85 (95% CI: 0.75–0.91), and 35.85 (95% CI: 10.68–120.28), respectively. The AUC for blood procalcitonin was 0.921. Blood procalcitonin also showed higher diagnostic accuracy for detecting bacterial meningitis than other conventional biomarkers, including serum C-reactive protein and leukocyte count, CSF leukocyte and neutrophil count, and CSF protein and glucose levels. Blood procalcitonin can be a good supplemental biomarker with high diagnostic accuracy in detecting bacterial meningitis in children.

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