Both Ultrasound Features and Nuclear Atypia are Associated with Malignancy in Thyroid Nodules with Atypia of Undetermined Significance.

BACKGROUND: The optimal management of thyroid nodules that undergo fine-needle aspiration (FNA) with findings of atypia of undetermined significance (AUS) is unclear. Categorizing nodules by AUS subtype and ultrasound characteristics may improve risk stratification. Therefore, the purpose of this study is to evaluate the association between AUS subtype and ultrasound features on risk of malignancy (ROM). METHODS: We performed a review of all patients with a thyroid nodule who underwent an FNA at our institution between January 2010 and November 2015. Patients with AUS were divided into groups with (1) nuclear atypia, (2) architectural atypia, or (3) Hurthle cell atypia. Their ultrasound features were assessed using the American Thyroid Association (ATA) thyroid nodule sonographic patterns. We conducted a univariate and multivariable analysis to determine the association between AUS subtype and other variables of interest with ROM. RESULTS: Of the 3428 thyroid nodules that underwent FNA, 237 (6.9%) had AUS. Of the 97 surgically resected nodules, 67 (69%) were benign and 30 (31%) were malignant. On univariate analysis nuclear atypia (p < 0.01) was associated with a thyroid malignancy. On multivariable analysis, both ATA high-risk ultrasound features (p = 0.04, odds ratio [OR] 3.68) and nuclear atypia (p < 0.01, OR 11.8) were independently associated with a final diagnosis of thyroid carcinoma. CONCLUSIONS: Nuclear atypia and ATA high-risk ultrasound features are useful in identifying patients with AUS that are at a higher risk of thyroid malignancy. Surgeons should take these factors into consideration when evaluating patients with AUS.

Targeting quinolone- and aminocoumarin-resistant bacteria with new gyramide analogs that inhibit DNA gyrase.

Bacterial DNA gyrase is an essential type II topoisomerase that enables cells to overcome topological barriers encountered during replication, transcription, recombination, and repair. This enzyme is ubiquitous in bacteria and represents an important clinical target for antibacterial therapy. In this paper we report the characterization of three exciting new gyramide analogs-from a library of 183 derivatives-that are potent inhibitors of DNA gyrase and are active against clinical strains of gram-negative bacteria (Escherichia coli, Shigella flexneri, and Salmonella enterica; 3 of 10 wild-type strains tested) and gram-positive bacteria (Bacillus spp., Enterococcus spp., Staphylococcus spp., and Streptococcus spp.; all 9 of the wild-type strains tested). E. coli strains resistant to the DNA gyrase inhibitors ciprofloxacin and novobiocin display very little cross-resistance to these new gyramides. In vitro studies demonstrate that the new analogs are potent inhibitors of the DNA supercoiling activity of DNA gyrase (IC50s of 47-170 nM) but do not alter the enzyme's ATPase activity. Although mutations that confer bacterial cells resistant to these new gyramides map to the genes encoding the subunits of the DNA gyrase (gyrA and gyrB genes), overexpression of GyrA, GyrB, or GyrA and GyrB together does not suppress the inhibitory effect of the gyramides. These observations support the hypothesis that the gyramides inhibit DNA gyrase using a mechanism that is unique from other known inhibitors.