The TIRADS has allowed us to improve patient management and cost-effectiveness, avoiding unnecessary FNAB. In addition, we have established standard codes to be used both for radiologists and endocrinologists.
• TIRADS classification allows accurate selection of thyroid nodules requiring biopsy (TIRADS 4-5). • The recognition of benign/possibly benign patterns can avoid unnecessary procedures. • This classification and its sonographic patterns are validated using surgical specimens.
Background: In most of the world, diagnostic surgery remains the most frequent approach for indeterminate thyroid cytology. Although several molecular tests are available for testing in centralized commercial laboratories in the United States, there are no available kits for local laboratory testing. The aim of this study was to develop a prototype in vitro diagnostic (IVD) gene classifier for the further characterization of nodules with an indeterminate thyroid cytology.Methods: In a first stage, the expression of 18 genes was determined by quantitative polymerase chain reaction (qPCR) in a broad histopathological spectrum of 114 fresh-tissue biopsies. Expression data were used to train several classifiers by supervised machine learning approaches. Classifiers were tested in an independent set of 139 samples. In a second stage, the best classifier was chosen as a model to develop a multiplexed-qPCR IVD prototype assay, which was tested in a prospective multicenter cohort of fine-needle aspiration biopsies.Results: In tissue biopsies, the best classifier, using only 10 genes, reached an optimal and consistent performance in the ninefold cross-validated testing set (sensitivity 93% and specificity 81%). In the multicenter cohort of fine-needle aspiration biopsy samples, the 10-gene signature, built into a multiplexed-qPCR IVD prototype, showed an area under the curve of 0.97, a positive predictive value of 78%, and a negative predictive value of 98%. By Bayes' theorem, the IVD prototype is expected to achieve a positive predictive value of 64–82% and a negative predictive value of 97–99% in patients with a cancer prevalence range of 20–40%.Conclusions: A new multiplexed-qPCR IVD prototype is reported that accurately classifies thyroid nodules and may provide a future solution suitable for local reference laboratory testing.
Summary
Enzootic diarrhea of calves has formed a serious problem and caused losses for years in the dairy herd kept at Vienna Veterinary University's Field Station. In previous investigations bovine coronavirus had been determined as the most pathogenic enteric agent, bovine rotavirus as secondary causal virus, whereas enteropathogenic E. coli and Cryptosporidia were present but insignificant causally. Two earlier systematic immunoprophylactic trials to reduce the incidence and severity of diarrheas of newborn calves failed. Vaccinating pregnant dams twice with a trivalent commercial vaccine containing live attenuated rotavirus and coronavirus plus K 99 + antigen of E. coli (Scourguard 3 [R]) mediated most remarkable results. These were recorded clinically and were assessed by performing daily ELISAs on calf fecal samples up to day 14 after birth for both rotavirus and coronavirus antigens.
Shedding of enteropathogenic E. coli and of cryptosporidia were also controlled. Furthermore, antibody titres against rotavirus and coronavirus were determined in cows' blood serum, colostrum and whole milk as well as in calf sera, including control data from unvaccinated cows and their offspring. In addition, a number of calves originating from vaccinated or unvaccinated dams were perorally challenged with rotavirus and coronavirus, again daily screening their fecal samples for virus‐shedding by ELISA. Very remarkable protective effects of dam vaccination were found clinically as well as regarding the number and shortened duration of calf shedding of rotavirus. None of 242 fecal samples contained coronavirus and none of 80 contained enteropathogenic E. coli. It is emphasized that calves must be fed milk of their vaccinated dams for a full 14 days after birth, so as to extend the continuous lactogenic immunity over the period of maximal susceptibility to the 3 enteropathogenic agents incorporated in the vaccine.
Zusammenfassung
Reduktion der mit Rotavirus, Coronavirus und E. coli assoziierten Durchfälle neugeborener Kälber in einem großen Milchviehbestand durch Mutterkuh‐Impfungen mittels eines trivalenten Impfstoffes
Enzootische Kälberdurchfälle bildeten seit Jahren ein ernsthaftes Problem und verursachten Verluste in der Rinderherde des Lehr‐ und Forschungsgutes der Veterinärmedizinischen Universität Wien. In früheren Erhebungen hatten wir ermittelt, daß bovines Coronavirus das Agens von höchster Pathogenität darstellte, daß bovines Rotavirus causal als zweitwichtigster Erreger fungierte, wogegen enteropathogene E. coli und Cryptosporidien wohl vorhanden aber ohne ursächliche Bedeutung für das Durchfallgeschehen waren. Zwei frühere systematische immunoprophylaktische Versuche, Häufigkeit wie Schweregrad der Durchfälle neugeborener Kälber zu reduzieren, hatten ihr Ziel nicht erreicht. Demgegenüber erbrachte nunmehr die zweimalige Schutzimpfung trächtiger Kühe mittels eines trivalenten Marktimpfstoffs, welcher lebende attenuierte Rotaviren und Coronaviren plus K 99 + Antigen von E. coli enthält (Scourguard 3 [R]), sehr bemerke...
Our study suggests that the presence of thyroid microcalcifications without a nodule is suspicious for PTC. We found that both patterns were suspicious for PTC, particularly in young patients. Special concern arises for those clustered microcalcifications on a background of Hashimoto thyroiditis.
Background: Although most thyroid nodules with indeterminate cytology are benign, in most of the world, surgery remains as the most frequent diagnostic approach. We have previously reported a 10-gene thyroid genetic classifier, which accurately predicts benign thyroid nodules. The assay is a prototype diagnostic kit suitable for reference laboratory testing and could potentially avoid unnecessary diagnostic surgery in patients with indeterminate thyroid cytology. Methods: Classifier performance was tested in two independent, ethnically diverse, prospective multicenter trials (TGCT-1/Chile and TGCT-2/USA). A total of 4061 fine-needle aspirations were collected from 15 institutions, of which 897 (22%) were called indeterminate. The clinical site was blind to the classifier score and the clinical laboratory blind to the pathology report. A matched surgical pathology and valid classifier score was available for 270 samples. Results: Cohorts showed significant differences, including (i) clinical site patient source (academic, 43% and 97% for TGCT-1 and-2, respectively); (ii) ethnic diversity, with a greater proportion of the Hispanic population (40% vs. 3%) for TGCT-1 and a greater proportion of African American (11% vs. 0%) and Asian (10% vs. 1%) populations for TGCT-2; and (iii) tumor size (mean of 1.7 and 2.5 cm for TGCT-1 and-2, respectively).
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