Role of ultrasound in predicting telomerase reverse transcriptase (TERT) promoter mutation in follicular thyroid carcinoma.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. This study aimed to demonstrate the ultrasonographic (US) features of TERT promoter-mutated follicular thyroid cancer (FTC) and evaluate their predictive performance. A total of 63 patients with surgically confirmed FTC between August 1995 and April 2021 were included. All data were available for analysis of preoperative US findings and TERT promoter mutation results. Genomic DNA was extracted from the archived surgical specimens to identify TERT promoter mutations. Logistic regression analysis was performed to compare US findings between TERT promoter-mutated and wild-type FTCs. Of the 63 patients with FTC, 10 (15.9%) had TERT promoter mutations. TERT promoter-mutated FTCs demonstrated significantly different US suspicion categories compared to wild-type FTCs (Ps = 0.0054 for K-TIRADS and 0.0208 for ACR-TIRADS), with a trend toward an increasing prevalence of the high suspicion category (40.0% for both K-TIRADS and ACR-TIRADS; Ps for trend = 0.0030 for K-TIRADS and 0.0032 for ACR-TIRADS). Microlobulated margins and punctate echogenic foci were independent risk factors associated with TERT promoter mutation in FTC (odds ratio = 9.693, 95% confidence interval = 1.666-56.401, p = 0.0115 for margins; odds ratio = 8.033, 95% confidence interval = 1.424-45.309, p = 0.0182 for punctate echogenic foci). There were no significant differences in the composition and echogenicity of the TERT promoter-mutated and wild-type FTCs. TERT promoter-mutated FTCs were categorized more frequently as high suspicion by the K-TIRADS and ACR-TIRADS. Based on US findings, the independent risk factors for TERT promoter mutations in FTC are microlobulated margins and punctate echogenic foci.

Association of Ultrasonography Features of Follicular Thyroid Carcinoma With Tumor Invasiveness and Prognosis Based on WHO Classification and TERT Promoter Mutation.

OBJECTIVE: To investigate the association of ultrasound (US) features of follicular thyroid carcinoma (FTC) with tumor invasiveness and prognosis based on the World Health Organization (WHO) classification and telomerase reverse transcriptase (TERT) promoter mutations. MATERIALS AND METHODS: This retrospective study included 54 surgically confirmed FTC patients with US images and TERT promoter mutations (41 females and 13 males; median age [interquartile range], 40 years [30-51 years]). The WHO classification consisted of minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTCs. Alternative classifications included Group 1 (MI-FTC and EA-FTC with wild type TERT), Group 2 (WI-FTC with wild type TERT), and Group 3 (EA-FTC and WI-FTC with mutant TERT). Each nodule was categorized according to the US patterns of the Korean Thyroid Imaging Reporting and Data System (K-TIRADS) and American College of Radiology-TIRADS (ACR-TIRADS). The Jonckheere-Terpstra and Cochran-Armitage tests were used for statistical analysis. RESULTS: Among 54 patients, 29 (53.7%) had MI-FTC, 16 (29.6%) had EA-FTC, and nine (16.7%) had WI-FTC. In both the classifications, lobulation, irregular margins, and final assessment categories showed significant differences (all Ps ≤ 0.04). Furthermore, the incidences of lobulation, irregular margin, and high suspicion category tended to increase with increasing tumor invasiveness and worse prognosis (all Ps for trend ≤ 0.006). In the WHO groups, hypoechogenicity differed significantly among the groups (P = 0.01) and tended to increase in proportion as tumor invasiveness increased (P for trend = 0.02). In the alternative group, punctate echogenic foci were associated with prognosis (P = 0.03, P for trend = 0.03). CONCLUSION: Increasing tumor invasiveness and worsening prognosis in FTC based on the WHO classification and TERT promoter mutation results were positively correlated with US features that indicate malignant probability according to both K-TIRADS and ACR-TIRADS.

Combination of Dabrafenib and Trametinib in Patients with Metastatic BRAFV600E-Mutated Thyroid Cancer.

Purpose: BRAF mutations are detected in 30-80% of papillary thyroid cancer (PTC) cases. Dabrafenib and trametinib showed promising antitumor activity in patients with BRAFV600E-mutated metastatic melanoma and non-small cell lung cancer. This study aimed to evaluate the efficacy and safety of dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated thyroid cancer. Materials and Methods: This was a retrospective study to evaluate the efficacy of dabrafenib and trametinib in patients with metastatic BRAFV600E-mutated PTC. The patients received dabrafenib 150 mg twice daily and trametinib 2 mg once daily at the Samsung Medical Center. This study evaluated the progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) overall survival (OS), and safety of dabrafenib and trametinib. Results: Between December 2019 and January 2022, 27 PTC patients including 8 patients with poorly differentiated or anaplastic transformation, received dabrafenib and trametinib. The median age was 73.0 years, and the median follow-up period was 19.8 months. The majority (81.5%) had undergone thyroidectomy, while 8 patients had received prior systemic treatments. ORR was 73.1%, with 19 partial responses, and DCR was 92.3%. Median PFS was 21.7 months, and median OS was 21.7 months. Treatment-related adverse events included generalized weakness (29.6%), fever (25.9%), and gastrointestinal problems (22.2%). Dose reduction due to adverse events was required in 81.5% of the patients. Conclusion: Dabrafenib and trametinib demonstrated a high ORR with promising PFS; however, most patients with BRAFV600E-mutated metastatic PTC required a dose reduction.

The association between TSH and thyroid hormones in the normal or subclinical dysfunction range with left ventricular diastolic dysfunction.

Thyroid hormones modulate the cardiovascular system. However, the effects of subclinical thyroid dysfunction and euthyroidism on cardiac function remain unclear. We investigated the association between left ventricular (LV) diastolic dysfunction and subclinical thyroid dysfunction or thyroid hormones within the reference range. This cross-sectional study included 26,289 participants (22,197 euthyroid, 3,671 with subclinical hypothyroidism, and 421 with subclinical thyrotoxicosis) who underwent regular health check-ups in the Republic of Korea. Individuals with thyroid stimulating hormone (TSH) levels > 4.2 µIU/mL and normal free thyroxine (FT4, 0.78-1.85 ng/dL) and triiodothyronine (T3, 76-190 ng/dL) levels were defined as having subclinical hypothyroidism. Individuals with serum TSH levels < 0.4 µIU/mL and normal FT4 and T3 levels were defined as having subclinical thyrotoxicosis. The cardiac structure and function were evaluated using echocardiography. LV diastolic dysfunction with normal ejection fraction (EF) was defined as follows: EF of > 50% and (a) E/e' ratio > 15, or (b) E/e' ratio of 8-15 and left atrial volume index ≥ 34 mL/m2. Subclinical hypothyroidism was significantly associated with cardiac indices regarding LV diastolic dysfunction. The odds of having LV diastolic dysfunction was also increased in participants with subclinical hypothyroidism (adjusted odds ratio [AOR] 1.36, 95% confidence interval [CI], 1.01-1.89) compared to euthyroid participants. Subclinical thyrotoxicosis was not associated with LV diastolic dysfunction. Among the thyroid hormones, only serum T3 was significantly and inversely associated with LV diastolic dysfunction even within the normal range. Subclinical hypothyroidism was significantly associated with LV diastolic dysfunction, whereas subclinical thyrotoxicosis was not. Serum T3 is a relatively important contributor to LV diastolic dysfunction compared to TSH or FT4.

Clinical Manifestations of Malignant Struma Ovarii: A Retrospective Case Series in a Tertiary Hospital in Korea.

BACKGRUOUND: Malignant struma ovarii (MSO) is a very rare disease in which thyroid cancer originates from the ovary. Because it is rare for endocrinologists to encounter patients with MSO, endocrinologists may have a limited understanding of the disease. Therefore, we analyzed and introduced its incidence and clinical course in a tertiary hospital in Korea. METHODS: We retrospectively investigated the clinical data of 170 patients who underwent surgery for struma ovarii at the Department of Obstetrics and Gynecology of Samsung Medical Center from 1994 to May 2023. RESULTS: Among 170 patients with struma ovarii, 15 (8.8%) were diagnosed with MSO. The median age of patients with MSO was 48 years (range, 30 to 74), and the median tumor size was 3.3 cm (range, 0.5 to 11.0). Papillary thyroid carcinoma (46.7%) was the most common subtypes followed by follicular thyroid carcinoma (26.7%). All patients were diagnosed after surgery, with no predictions from preoperative imaging. The surgical extent of gynecological surgery was variable. Four patients (26.7%) underwent thyroidectomy for thyroid cancer, while one underwent total thyroidectomy and radioactive iodine therapy for MSO with peritoneal metastasis. Except for one patient who underwent hemithyroidectomy, thyroid stimulating hormone suppression therapy was performed in four patients. Only 53% of MSO patients were consulted by an endocrinologist. With a median follow-up period of 33 months (range, 4 to 156), 11 patients remained disease-free, one experienced progression with peritoneal seeding, and the remaining one was in treatment. There have been no recurrences or deaths due to MSO. CONCLUSION: An endocrinologist should be involved in establishing a therapeutic plan for MSO, for which the overall prognosis is generally favorable.

Adequate Dose of Levothyroxine for Thyroid-Stimulating Hormone Suppression after Total Thyroidectomy in Patients with Differentiated Thyroid Cancer.

Background: The adequate dose of levothyroxine (LT4) for patients who have undergone total thyroidectomy (TT) for differentiated thyroid cancer (DTC) is uncertain. We evaluated the LT4 dose required to achieve mild thyroid-stimulating hormone (TSH) suppression in DTC patients after TT. Methods: The electronic medical records of patients who underwent TT for DTC and received mild TSH suppression therapy were reviewed. Linear regression analysis was performed to evaluate the association between LT4 dose (µg/kg) and an ordinal group divided by body mass index (BMI). We also evaluated the trend in LT4 doses among groups divided by BMI and age. Results: In total, 123 patients achieved mild TSH suppression (0.1 to 0.5 mIU/L). The BMI variable was divided into three categories: <23 kg/m2 (n=46), ≥23 and <25 kg/m2 (n=30), and ≥25 kg/m2 (n=47). In the linear regression analysis, BMI was negatively associated with the LT4 dose after adjusting for age and sex (P<0.001). The LT4 doses required to achieve mild TSH suppression based on the BMI categories were 1.86, 1.71, and 1.71 µg/kg, respectively (P for trend <0.001). Further analysis with groups divided by age and BMI revealed that a higher BMI was related to a lower LT4 dose, especially in younger patients aged 20 to 39 (P for trend=0.011). Conclusion: The study results suggest an appropriate LT4 dose for mild TSH suppression after TT based on body weight in patients with DTC. Considering body weight, BMI, and age in estimating LT4 doses might help to achieve the target TSH level promptly.

An ultra-sensitive colloidal quantum dot infrared photodiode exceeding 100 000% external quantum efficiency via photomultiplication.

In this study, we present ultrasensitive infrared photodiodes based on PbS colloidal quantum dots (CQDs) using a double photomultiplication strategy that utilizes the accumulation of both electron and hole carriers. While electron accumulation was induced by ZnO trap states that were created by treatment in a humid atmosphere, hole accumulation was achieved using a long-chain ligand that increased the barrier to hole collection. Interestingly, we obtained the highest responsivity in photo-multiplicative devices with the long ligands, which contradicts the conventional belief that shorter ligands are more effective for optoelectronic devices. Using these two charge accumulation effects, we achieved an ultrasensitive detector with a responsivity above 7.84 × 102 A W-1 and an external quantum efficiency above 105% in the infrared region. We believe that the photomultiplication effect has great potential for surveillance systems, bioimaging, remote sensing, and quantum communication.

Atto-Scale Noise Near-Infrared Organic Photodetectors Enabled by Controlling Interfacial Energetic Offset through Enhanced Anchoring Ability.

The near-infrared (NIR) sensor technology is crucial for various applications such as autonomous driving and biometric tracking. Silicon photodetectors (SiPDs) are widely used in NIR applications; however, their scalability is limited by their crystalline properties. Organic photodetectors (OPDs) have attracted attention for NIR applications owing to their scalability, low-temperature processing, and notably low dark current density (JD), which is similar to that of SiPDs. However, the still high JD (at NIR band) and few measurements of noise equivalent powers (NEPs) pose challenges for accurate performance comparisons. This study addresses these issues by quantitatively characterizing the performance matrix and JD generation mechanism using electron-blocking layers (EBLs) in OPDs. The energy offset at an EBL/photosensitive layer interface determines the thermal activation energy and directly affects JD. A newly synthesized EBL (3PAFBr) substantially enhances the interfacial energy barrier by forming a homogeneous contact owing to the improved anchoring ability of 3PAFBr. As a result, the OPD with 3PAFBr yields a noise current of 852 aA (JD = 12.3 fA cm⁻2 at V → -0.1 V) and several femtowatt-scale NEPs. As far as it is known, this is an ultralow of JD in NIR OPDs. This emphasizes the necessity for quantitative performance characterization.