scholarly journals Serum Thyroglobulin (Tg) Monitoring of Patients with Differentiated Thyroid Cancer Using Sensitive (Second-Generation) Immunometric Assays Can Be Disrupted by False-Negative and False-Positive Serum Thyroglobulin Autoantibody Misclassifications

2014 ◽  
Vol 99 (12) ◽  
pp. 4589-4599 ◽  
Author(s):  
Carole Spencer ◽  
Ivana Petrovic ◽  
Shireen Fatemi ◽  
Jonathan LoPresti

Context: Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay (2GIMA) measurements as free from TgAb interference and when reflexing “TgAb-positive” sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). Objective: The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for “positivity” influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. Methods: Serum Tg2GIMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥1.0 μg/L had false-negative and false-positive TgAb frequencies determined using low Tg2GIMA/TgRIA ratios (<75%) to indicate TgAb interference. Results: TgAb-negative patients with disease displayed Tg2GIMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%–100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg2GIMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg2GIMA + TgLC-MS/MS associated with TgRIA of ≥1.0 μg/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%–32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg2GIMA, <0.10 μg/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%. Conclusions: Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yiqiu Shen ◽  
Farah E. Shamout ◽  
Jamie R. Oliver ◽  
Jan Witowski ◽  
Kawshik Kannan ◽  
...  

AbstractThough consistently shown to detect mammographically occult cancers, breast ultrasound has been noted to have high false-positive rates. In this work, we present an AI system that achieves radiologist-level accuracy in identifying breast cancer in ultrasound images. Developed on 288,767 exams, consisting of 5,442,907 B-mode and Color Doppler images, the AI achieves an area under the receiver operating characteristic curve (AUROC) of 0.976 on a test set consisting of 44,755 exams. In a retrospective reader study, the AI achieves a higher AUROC than the average of ten board-certified breast radiologists (AUROC: 0.962 AI, 0.924 ± 0.02 radiologists). With the help of the AI, radiologists decrease their false positive rates by 37.3% and reduce requested biopsies by 27.8%, while maintaining the same level of sensitivity. This highlights the potential of AI in improving the accuracy, consistency, and efficiency of breast ultrasound diagnosis.


2017 ◽  
Vol 107 (6) ◽  
pp. 721-731 ◽  
Author(s):  
Daniel D. M. Bassimba ◽  
Jose L. Mira ◽  
Antonio Vicent

Alternaria brown spot (ABS) is a serious fungal disease of mandarin in the Mediterranean Basin. Due to the rigorous fruit quality standards, models for ABS should avoid false negatives. Experiments were conducted with susceptible ‘Fortune’ and ‘Nova’ inoculated at different temperatures and leaf wetness durations, including interrupted periods. Effects of temperature and time elapsed after inoculation were also studied. Disease incidence data were fitted to generalized additive models and a generic infection model. Exposure of trap plants in affected orchards was used for model evaluation, including the Alter-Rater and a simple rule system (SRS). The predictive ability of the models was analyzed using the partial area under the receiver operating characteristic curve in the high-sensitivity range between 0.9 and 1. Postinoculation temperature had a significant effect on disease incidence, with maximum symptom expression after 30 h on Fortune and 60 h on Nova. ABS incidence did not increase after a leaf wetness interruption of 1 h on Nova and 2 h on Fortune. All the models evaluated had high false-positive rates on Fortune. Only the SRS showed a substantial strength of agreement in Nova, with a true-positive rate of 0.93 and false-positive rate of 0.16.


2005 ◽  
Vol 63 (2) ◽  
Author(s):  
L. Montella ◽  
M. Caraglia ◽  
A. Abbruzzese ◽  
A. Soricelli ◽  
M. Caputi ◽  
...  

The follow-up of Differentiated Thyroid Cancer conventionally includes serum thyroglobulin and periodic Whole Body Scans. The uptake of 131-I in normal and pathological tissues different from metastatic thyroid cancer sites is a cause of false-positive scans. Among them, mediastinal uptake caused by thymic hyperplasia can be observed. The aim of the present study was to review a series of 573 patients with differentiated thyroid cancer treated with 131-I after surgery between 1992 and 2003 looking above all for those with mediastinal images resembling thymus. This evaluation is presented together with some hypotheses on the relationships between thymus and thyroid. Moreover, some considerations are made on the differential diagnosis between thymus and mediastinal tumour thyroid residues.


Author(s):  
Blertina Dyrmishi ◽  
Taulant Olldashi ◽  
Ema Lumi ◽  
Entela Puca ◽  
Dorina Ylli ◽  
...  

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Shili Jiang ◽  
Wei Jiang ◽  
Ying Xu ◽  
Xiaoning Wang ◽  
Yongping Mu ◽  
...  

Background and Objective: Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B. </P><P> Methods: Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis. Results: Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001). Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.


2019 ◽  
Vol 30 (7-8) ◽  
pp. 221-228
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh ◽  
Nicholas Hobbs ◽  
Jigar Shah ◽  
Matthew Harris ◽  
...  

Aims To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. Methods Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. Results Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. Conclusions As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.


Author(s):  
Amaia Sandúa ◽  
Monica Macias ◽  
Carolina Perdomo ◽  
Juan Carlos Galofre ◽  
Roser Ferrer ◽  
...  

AbstractBackgroundThyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay.MethodsWe retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays.ResultsrhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL.ConclusionsPatients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.


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