Alemtuzumab-induced autoimmune thyroid events in patients with relapsing-remitting multiple sclerosis: A real-life and monocentric experience at a tertiary-level centre.

OBJECTIVE: Alemtuzumab-induced autoimmune thyroid events (AIATEs) are the most common adverse effects observed in relapsing-remitting multiple sclerosis (RRMS) patients. This study aims to explore the clinical and biochemical characteristics of such AIATEs, and to examine the risk factors for their occurrence, particularly for the worst clinical phenotype of fluctuating Graves' disease (GD). DESIGN, PATIENTS, MEASUREMENTS: We retrospectively analysed a real-life single-centre consecutive series of 57 RRMS patients treated with alemtuzumab whose clinical and biochemical parameters were collected before starting the treatment and then monthly during their follow-up. RESULTS: AIATEs developed in 39% of patients a mean 17 months ± 11 after the first cycle of alemtuzumab. The most common AIATEs were GD (64%), followed by Hashimoto's thyroiditis with hypothyroidism (23%), TSH-receptor-antibody (TRAb)-positive hypothyroidism (9%), and silent thyroiditis (4%). GD showed a fluctuating course in 57% of cases. Baseline positivity for anti-thyroperoxidase antibodies, and higher absolute titers of anti-thyroglobulin and anti-thyroperoxidase antibodies correlated significantly with the risk of developing AIATEs, but TRAb positivity did not. Higher TRAb titers at the time of GD being diagnosed correlated strongly with a greater risk of the fluctuating GD phenotype. On ROC curve analysis, we found that a cut-off of 7.3 IU/L could be used to predict the risk of developing a fluctuating GD, with a positive predictive value of 100%. CONCLUSIONS: TRAb levels measured with commercial automatic methods at the time of a patient being diagnosed with alemtuzumab-induced GD emerged as a novel biomarker for predicting a fluctuating disease phenotype, with an influence on subsequent therapeutic decisions and patients' follow-up.

Circulating miR-146a predicts glucocorticoid response in thyroid eye disease.

Objective: Thyroid eye disease (TED) is an immune-mediated disorder of the eye. Intravenous glucocorticoid (GC) is the first-line treatment for patients with active moderate-to-severe TED. However, the response rate is between 50% and 80%. There are still no simple and reliable markers of responsiveness to GC therapy. We aimed to explore the possible role of miR-146a and miR-21 as predictors of responsiveness to GC treatment in TED. Methods: We carried out a prospective longitudinal study on 30 consecutive adult patients with active moderate-to-severe TED and eligible for GC therapy. All patients received the standard GC treatment with methylprednisolone i.v. In cases of progressive worsening of Gorman Score for diplopia or with duction restriction <30° in at least two consecutive controls, patients also underwent orbital radiotherapy. Response to GC treatment was defined as a decrease of two or more points in the clinical activity score (CAS) or CAS <4/10 at 24 weeks. Circulating miRNAs were extracted from patients' serum and quantified by real-time PCR. Results: Twenty-three (77%) patients responded to GC. Thyroid surgery, higher CAS, greater proptosis and higher pre-treatment circulating levels of miR-146a emerged as predictive factors of responsiveness to GC. A ROC analysis revealed that miR-146a could predict responsiveness to GC with a positive predictive value of 100%. Conclusion: This is the first study investigating the role of pre-treatment circulating miR-21 and miR-146a to predict responsiveness to GC in TED. miR-146a emerged as a simple, objective, new marker of GC sensitivity that could be used to avoid ineffective administration of GC therapy to TED patients.

The role of the size in thyroid cancer risk stratification.

Only a minority of cases of differentiated thyroid carcinoma (DTC) have a poor clinical outcome. Clinical outcomes and molecular aspects were assessed in: 144 DTC ≤ 40 mm without distant metastases (group 1); 50 DTC > 40 mm without distant metastases (group 2); and 46 DTC with distant metastases (group 3). Group 3 had a worse outcome than the other two groups: during the follow-up, patients more frequently had persistent disease, died, or underwent further treatment. The outcomes did not differ between groups 1 and 2. Group 3 had a higher prevalence of TERT promoter mutations than group 2 (32.6% vs 14%). Group 1 had a higher frequency of BRAF mutations than groups 2 or 3 (61.1% vs 16.0% and 26.1%, respectively), while RAS mutations were more common in group 2 than in groups 1 and 3 (16.0% vs 2.1% and 6.5%, respectively). Groups 1 and 2 shared the same outcome, but were genetically distinct. Only lymph node involvement, distant metastases, older age and (among the molecular markers) TERT promoter mutations were independent predictors of a worse outcome. Metastatic DTC had the worst outcome, while the outcome was identical for large and small non-metastatic DTC, although they showed different molecular patterns. TERT promoter mutations emerged as an independent factor pointing to a poor prognosis.

Transcriptional profiling by DDRT-PCR analysis reveals gene expression during seed development in Carya cathayensis Sarg.

Hickory (Carya cathayensis Sarg.) seed has one of the highest oil content and is rich in polyunsaturated fatty acids (PUFAs), which kernel is helpful to human health, particularly to human brain function. A better elucidation of lipid accumulation mechanism would help to improve hickory production and seed quality. DDRT-PCR analysis was used to examine gene expression in hickory at thirteen time points during seed development process. A total of 67 unique genes involved in seed development were obtained, and those expression patterns were further confirmed by semi-quantitative RT-PCR and real time RT-PCR analysis. Of them, the genes with known functions were involved in signal transduction, amino acid metabolism, nuclear metabolism, fatty acid metabolism, protein metabolism, carbon metabolism, secondary metabolism, oxidation of fatty acids and stress response, suggesting that hickory underwent a complex metabolism process in seed development. Furthermore, 6 genes related to fatty acid synthesis were explored, and their functions in seed development process were further discussed. The data obtained here would provide the first clues for guiding further functional studies of fatty acid synthesis in hickory.

Identification of liguzinediol metabolites in rats by ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry.

Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/QTOF MS) was employed to investigate the in vivo metabolism of liguzinediol. Urine, bile, feces and plasma samples were collected after intravenous administration of 10mg/kg liguzinediol to healthy rats. Altogether seven metabolites were detected and tentatively identified based on the characteristics of their protonated ions. The metabolites were mainly transformed by four main metabolic pathways including oxidation, sulfation, glycine conjugation and glucuronidation.