Association of Antithyroid Antibodies in Checkpoint Inhibitor-Associated Thyroid Immune-Related Adverse Events.

CONTEXT: The significance of thyroid peroxidase (TPOAb) and thyroglobulin antibody (TgAb) in the pathogenesis of thyroid immune-related adverse events (irAEs) is unknown. OBJECTIVE: To characterize the association of anti-thyroid antibodies with the development of thyroid immune related adverse events. METHODS: A retrospective cohort study was conducted of patients with melanoma receiving immune checkpoint inhibitor (ICI) treatment. TPOAb, TgAb, and interleukin-6 (IL-6) were measured retrospectively using tumor-banked samples at baseline and at time of diagnosis of a thyroid irAE. In euthyroid patients (without thyroid irAEs) measures were repeated 30 to 60 days after ICI commencement, which was similar to the median time to onset of thyroid irAEs in other patients. RESULTS: A total of 122 patients were included-31 remained euthyroid, 47 developed subclinical thyrotoxicosis, 37 developed overt thyrotoxicosis, and 7 developed overt hypothyroidism without preceding thyrotoxicosis. Baseline elevation of TPOAb or TgAb was present in 19 (16%) and 28 (23%) patients, respectively. Positive TPOAb or TgAb at baseline was 97% and 100% specific for eventual development of a thyroid irAE, respectively. During ICI treatment, overt thyrotoxicosis, but not other subtypes of thyroid irAE, was associated with statistically significant increases in the titer of TgAb and TPOAb. Baseline IL-6 levels were not associated with thyroid irAE onset but statistically significantly increased during treatment in patients who developed overt hypothyroidism. CONCLUSIONS: TPOAb and TgAb positivity at baseline was more prevalent in patients who developed thyroid irAEs. Statistically significant increases or new antibody positivity was observed in association with overt thyrotoxicosis. TPOAb and TgAb positivity or increases during ICI treatment may be a useful biomarker to identify patients at increased risk of thyroid irAEs, particularly overt thyrotoxicosis.

Treatment timing for rapid maxillary expansion.

The aim of this study was to evaluate the short-term and long-term treatment effects of rapid maxillary expansion in 2 groups of subjects treated with the Haas appliance. Treatment outcomes were evaluated before and after the peak in skeletal maturation, as assessed by the cervical vertebral maturation (CVM) method, in a sample of 42 patients compared to a control sample of 20 subjects. Posteroanterior cephalograms were analyzed for the treated subjects at T1 (pretreatment), T2 (immediate post-expansion) and T3 (long-term observation), and were available at T1 and at T3 for the controls. The mean age (years: months) at T1 was 11:10 for both the treated and the control groups. The mean ages at T3 also were comparable (20:6 for the treated group and 17:8 for the controls). Following expansion and retention (2 months on average), fixed standard edgewise appliances were placed. The study included transverse measurements on dentoalveolar structures, maxillary and mandibular bases and other craniofacial regions (nasal, zygomatic, orbital, and cranial). Treated and control samples were divided into 2 groups according to individual skeletal maturation. The early-treated and early-control groups had not reached the pubertal peak in skeletal growth velocity at T1 (CVM 1 to 3), whereas the late-treated and late-control groups were during or slightly after the peak at T1 (CVM 4 to 6). The group treated before the pubertal peak showed significantly greater short-term increases in the width of the nasal cavities. In the long-term, maxillary skeletal width, maxillary intermolar width, lateronasal width, and lateroorbitale width were significantly greater in the early-treated group. The late-treated group exhibited significant increases in lateronasal width and in maxillary and mandibular intermolar widths. Rapid Maxillary Expansion treatment before the peak in skeletal growth velocity is able to induce more pronounced transverse craniofacial changes at the skeletal level.