Outcomes of cytologically indeterminate thyroid nodules managed with Genomic Sequencing Classifier.

CONTEXT: Molecular testing can refine the risk of malignancy in thyroid nodules with indeterminate cytology to decrease unnecessary diagnostic surgery. OBJECTIVE: This study was performed to evaluate the outcomes of cytologically indeterminate thyroid nodules managed with Afirma genomic sequencing classifier (GSC) testing. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Adult patients who underwent a biopsy at three major academic centers between July 2017 and June 2021 with Bethesda III or IV cytology were included. All patients had surgery or minimum follow-up of 1 year ultrasound surveillance. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity, specificity, PPV, and NPV of GSC in Bethesda III and IV nodules. RESULTS: The median nodule size of the 834 indeterminate nodules was 2.1 cm and the median follow-up was 23 months. GSC's sensitivity, specificity, PPV, and NPV across all institutions were 95%, 81%, 50%, and 99% for Bethesda III nodules and 94%, 82%, 65%, and 98% for Bethesda IV nodules, respectively. The overall false negative rate was 2%. The NPV of GSC in thyroid nodules with oncocytic predominance was 100% in Bethesda III nodules and 98% in Bethesda IV nodules. However, the PPV of oncocytic nodules was low (17% in Bethesda III nodules and 45% in Bethesda IV nodules). Only 22% of thyroid nodules with benign GSC results grew during surveillance. CONCLUSIONS: GSC is a key tool for managing patients with indeterminate cytology, including the higher-risk Bethesda IV category. GSC benign thyroid nodules can be observed similarly to thyroid nodules with benign cytology.

Diagnostic performance of molecular testing in indeterminate (Bethesda III and IV) thyroid nodules with Hürthle cell cytology.

BACKGROUND: Indeterminate thyroid nodules with Hürthle cell cytology remain a diagnostic challenge. The low benign call rate and positive predictive value of first-generation molecular tests precluded their use to rule out malignancy. We examined the diagnostic performance of current tests. METHOD: This subset analysis of our prospective randomized trial compared the benign call rate and positive predictive value of Afirma Gene Sequencing Classifier and Thyroseq v3 in Bethesda III and IV nodules with Hürthle cell cytology. Molecular test samples were obtained at initial fine-needle aspiration (8/2017-7/2022) and reflexively sent for processing. RESULTS: Molecular testing was performed on 140 Hürthle cell nodules. Of 79 nodules tested with the Afirma Gene Sequencing Classifier, the benign call rate was 84% (66/79). Nine of 66 nodules with benign results were resected, with no malignancies. Twelve of 13 nodules with suspicious results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and one Hürthle cell carcinoma (positive predictive value 25%). Of 61 nodules tested with Thyroseq v3, the benign call rate was 56% (34/61; (P < .01 versus Afirma Gene Sequencing Classifier). Five of 34 nodules with negative results were resected, with no malignancies. Nineteen of 27 nodules with positive results were resected, revealing 3 malignancies-2 papillary thyroid carcinomas and 1 Hürthle cell carcinoma (positive predictive value 16%). CONCLUSION: The high benign call rate of current molecular tests in Hürthle cell nodules strengthens their value in enabling patients to avoid surgery.

Bethesda III and IV Thyroid Nodules Managed Nonoperatively After Molecular Testing With Afirma GSC or Thyroseq v3.

CONTEXT: Molecular testing has improved risk stratification and increased nonoperative management for patients with indeterminate thyroid nodules, but data on the long-term outcomes of current molecular tests Afirma Gene Sequencing Classifier (GSC) and Thyroseq v3 are limited. OBJECTIVE: To determine the rate of delayed operation and the false negative rate of the Afirma GSC and Thyroseq v3 in Bethesda III and IV thyroid nodules. METHODS: Prospective follow-up of a single center, randomized, clinical trial comparing the performance of Afirma GSC and Thyroseq v3 in the diagnosis of indeterminate thyroid nodules at the University of California, Los Angeles (UCLA). Consecutive participants who underwent thyroid biopsy in the UCLA health system with Bethesda III and IV cytology from August 2017 to November 2019. The main outcome measure was false negative rate of molecular testing. RESULTS: Of 176 indeterminate nodules with negative or benign molecular test results, 14 (8%) nodules underwent immediate resection, with no malignancies found on surgical pathology. Nonoperative management with active surveillance was pursued for 162 (92%) nodules with benign or negative test results. The median surveillance was 34 months (range 12-60 months), and 44 patients were lost to follow-up. Of 15 nodules resected during surveillance, 1 malignancy was found (overall false negative rate of 0.6%). This was a 2.7 cm minimally invasive Hurthle cell carcinoma that initially tested negative with Thyroseq v3 and underwent delayed resection due to sonographic growth during surveillance. CONCLUSIONS: The majority of Bethesda III/IV thyroid nodules with negative or benign molecular test results are stable over 3 years of follow-up. These findings support the high sensitivity of current molecular tests and their role in ruling out malignancy in indeterminate thyroid nodules.

Nanomedicine Approaches Against Parasitic Worm Infections.

Nanomedicine approaches have the potential to transform the battle against parasitic worm (helminth) infections, a major global health scourge from which billions are currently suffering. It is anticipated that the intersection of two currently disparate fields, nanomedicine and helminth biology, will constitute a new frontier in science and technology. This progress report surveys current innovations in these research fields and discusses research opportunities. In particular, the focus is on: (1) major challenges that helminth infections impose on mankind; (2) key aspects of helminth biology that inform future research directions; (3) efforts to construct nanodelivery platforms to target drugs and genes to helminths hidden in their hosts; (4) attempts in applying nanotechnology to enable vaccination against helminth infections; (5) outlooks in utilizing nanoparticles to enhance immunomodulatory activities of worm-derived factors to cure allergy and autoimmune diseases. In each section, achievements are summarized, limitations are explored, and future directions are assessed.