Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma.

BACKGROUND: Telomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined. METHODS: A total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups. RESULTS: The number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11-131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no-RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1-3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all-cause, thyroid cancer-specific, or SPM-specific mortality. CONCLUSIONS: In patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high-dose RAI treatment.

Prevalence, Treatment Status, and Comorbidities of Hyperthyroidism in Korea from 2003 to 2018: A Nationwide Population Study.

BACKGRUOUND: This study aimed to investigate the changes of incidence and treatment of choice for hyperthyroidism from 2003 to 2018 and explore the treatment-related complications and concomitant comorbidities in South Korea using data from the National Health Insurance Service. METHODS: This is a retrospective observational study. Hyperthyroidism was defined as a case having two or more diagnostic codes of thyrotoxicosis, with antithyroid drug intake for more than 6 months. RESULTS: The average age-standardized incidence of hyperthyroidism from 2003 to 2018 was 42.23 and 105.13 per 100,000 men and women, respectively. In 2003 to 2004, hyperthyroidism was most often diagnosed in patients in their 50s, but in 2017 to 2018, people were most often diagnosed in their 60s. During the entire period, about 93.7% of hyperthyroidism patients were prescribed with antithyroid drugs, and meanwhile, the annual rates of ablation therapy decrease from 7.68% in 2008 to 4.56% in 2018. Antithyroid drug-related adverse events, mainly agranulocytosis and acute hepatitis, as well as complications of hyperthyroidism such as atrial fibrillation or flutter, osteoporosis, and fractures, occurred more often in younger patients. CONCLUSION: In Korea, hyperthyroidism occurred about 2.5 times more in women than in men, and antithyroid drugs were most preferred as the first-line treatment. Compared to the general population, hyperthyroid patients may have a higher risk of atrial fibrillation or flutter, osteoporosis, and fractures at a younger age.

Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum: 2023 Revised Korean Thyroid Association Guidelines.

Thyroid hormone plays a critical role in fetal growth and development, and thyroid dysfunction during pregnancy is associated with several adverse outcomes, such as miscarriage and preterm birth. In this review, we introduce and explain three major changes in the revised Korean Thyroid Association (KTA) guidelines for the diagnosis and management of thyroid disease during pregnancy: first, the normal range of thyroid-stimulating hormone (TSH) during pregnancy; second, the treatment of subclinical hypothyroidism; and third, the management of euthyroid pregnant women with positive thyroid autoantibodies. The revised KTA guidelines adopt 4.0 mIU/L as the upper limit of TSH in the first trimester. A TSH level between 4.0 and 10.0 mIU/L, combined with free thyroxine (T4) within the normal range, is defined as subclinical hypothyroidism, and a TSH level over 10 mIU/L is defined as overt hypothyroidism regardless of the free T4 level. Levothyroxine treatment is recommended when the TSH level is higher than 4 mIU/L in subclinical hypothyroidism, regardless of thyroid peroxidase antibody positivity. However, thyroid hormone therapy to prevent miscarriage is not recommended in thyroid autoantibody-positive women with normal thyroid function.

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

Risk of Adverse Pregnancy Outcomes in Young Women with Thyroid Cancer: A Systematic Review and Meta-Analysis.

This meta-analysis investigated whether thyroidectomy or radioactive iodine treatment (RAIT) in patients with differentiated thyroid cancer (DTC) was associated with an increase in adverse pregnancy outcomes, such as miscarriage, preterm delivery, and congenital malformations. A total of 22 articles (5 case-control and 17 case series studies) from 1262 studies identified through a literature search in the PubMed and EMBASE databases from inception up to 13 September 2021 were included. In patients with DTC who underwent thyroidectomy, the event rates for miscarriage, preterm labor, and congenital anomalies were 0.07 (95% confidence interval [CI], 0.05-0.11; 17 studies), 0.07 (95% CI, 0.05-0.09; 14 studies), and 0.03 (95% CI, 0.02-0.06; 17 studies), respectively. These results are similar to those previously reported in the general population. The risk of miscarriage or abortion was increased in patients with DTC when compared with controls without DTC (odds ratio [OR], 1.80; 95% CI, 1.28-2.53; I2 = 33%; 3 studies), while the OR values for preterm labor and the presence of congenital anomalies were 1.22 (95% CI, 0.90-1.66; I2 = 62%; five studies) and 0.73 (95% CI, 0.39-1.38; I2 = 0%; two studies) respectively, which showed no statistical significance. A subgroup analysis of patients with DTC according to RAIT revealed that the risk of miscarriage, preterm labor, or congenital anomalies was not increased in the RAIT group when compared with patients without RAIT. The results of this meta-analysis suggest that thyroid cancer treatment, including RAIT, is not associated with an increased risk of adverse pregnancy outcomes, including miscarriage, preterm labor, and congenital anomalies.

Skeletal effects of combined bisphosphonates treatment and parathyroidectomy in osteoporotic patients with primary hyperparathyroidism.

INTRODUCTION: Bone loss caused by primary hyperparathyroidism (PHPT) is an indication for parathyroidectomy (PTX). However, whether adding bisphosphonates would be superior to PTX alone to increase bone mass remains unclear. We thus aimed to compare the skeletal effects of the combination treatment of bisphosphonates and PTX with PTX alone. MATERIALS AND METHODS: In this retrospective analysis, bone mineral density (BMD) changes after 1 year of combination treatment and PTX alone were compared. We also analyzed the correlation between changes in serum biochemical parameters and BMD after 1 year of treatment in both groups. RESULTS: The baseline characteristics of patients treated with PTX alone (n = 24) and combination treatment (n = 26) were comparable. BMD significantly increased after 1 year of treatment in both groups (all p < 0.001), and the increase in BMD at the femur neck was higher in the PTX alone group than in the combination group (p = 0.011). There was a decreasing trend in serum alkaline phosphatase (ALP) levels in PTX alone compared to the combination treatment group (p = 0.053). In the study cohort, lower BMD and higher ALP levels at baseline were associated with higher 1-year BMD changes at all sites. Interestingly, a significant association was found between changes in ALP and BMD at the femur neck in the PTX alone group (p = 0.003), but abolished in the combination group (p = 0.946). CONCLUSIONS: There is no additional benefit of BMD in combination treatment with bisphosphonates and PTX over PTX alone in osteoporotic patients with PHPT. Combined bisphosphonate treatment might interfere with the increase in bone mass caused by PTX.

Assessment of Inter-Institutional Post-Operative Hypoparathyroidism Status Using a Common Data Model.

Post-thyroidectomy hypoparathyroidism may result in various transient or permanent symptoms, ranging from tingling sensation to severe breathing difficulties. Its incidence varies among surgeons and institutions, making it difficult to determine its actual incidence and associated factors. This study attempted to estimate the incidence of post-operative hypoparathyroidism in patients at two tertiary institutions that share a common data model, the Observational Health Data Sciences and Informatics. This study used the Common Data Model to extract explicitly specified encoding and relationships among concepts using standardized vocabularies. The EDI-codes of various thyroid disorders and thyroid operations were extracted from two separate tertiary hospitals between January 2013 and December 2018. Patients were grouped into no evidence of/transient/permanent hypoparathyroidism groups to analyze the likelihood of hypoparathyroidism occurrence related to operation types and diagnosis. Of the 4848 eligible patients at the two institutions who underwent thyroidectomy, 1370 (28.26%) experienced transient hypoparathyroidism and 251 (5.18%) experienced persistent hypoparathyroidism. Univariate logistic regression analysis predicted that, relative to total bilateral thyroidectomy, radical tumor resection was associated with a 48% greater likelihood of transient hypoparathyroidism and a 102% greater likelihood of persistent hypoparathyroidism. Moreover, multivariate logistic analysis found that radical tumor resection was associated with a 50% greater likelihood of transient hypoparathyroidism and a 97% greater likelihood of persistent hypoparathyroidism than total bilateral thyroidectomy. These findings, by integrating and analyzing two databases, suggest that this analysis could be expanded to include other large databases that share the same Observational Health Data Sciences and Informatics protocol.

Clinicopathological Characteristics and Recurrence-Free Survival of Rare Variants of Papillary Thyroid Carcinomas in Korea: A Retrospective Study.

BACKGROUND: We aimed to evaluate the clinicopathological features and biological behaviors of Korean thyroid cancer patients with rare variants of papillary thyroid carcinoma (PTC) to address the ambiguity regarding the prognostic consequences of these variants. METHODS: We retrospectively reviewed the medical records of 5,496 patients who underwent thyroid surgery for PTC, between January and December 2012, in nine tertiary hospitals. Rare PTC variants included tall cell (TCV), columnar cell (CCV), diffuse sclerosing (DSV), cribriform-morular (CMV), solid (SV), hobnail, and Warthin-like variants. Recurrence-free survival (RFS) was defined as the time from the date of thyroidectomy until recurrence. RESULTS: Rare variants accounted for 1.1% (n=63) of the PTC patients; with 0.9% TCV, 0.02% CCV, 0.1% DSV, 0.1% CMV, and 0.1% SV. The mean age of patients and primary tumor size were 42.1±13.1 years and 1.3±0.9 cm, respectively. Extrathyroidal extension and cervical lymph node metastasis were observed in 38 (60.3%) and 37 (58.7%) patients, respectively. Ultrasonographic findings revealed typical malignant features in most cases. During a median follow-up of 7 years, 6.3% of patients experienced a locoregional recurrence. The 5-year RFS rates were 71.4% in patients with DSV or SV, 95.9% for TCV, or CCV, and 100% for other variants. DSV emerged an independent risk factor associated with shorter RFS. CONCLUSION: In this multicenter Korean cohort, rare variants accounted for 1.1% of all PTC cases, with TCV being the most frequent subtype. DSV emerged as a significant prognostic factor for RFS.

Effect of Cigarette Smoking on Thyroid Cancer: Meta-Analysis.

BACKGROUND: Although smoking is generally carcinogenic, its effect on thyroid cancers is still subject to controversy. The purpose of this study was to summarize the role of smoking in relation to thyroid cancer occurrence. METHODS: We performed a meta-analysis of 24 eligible studies: 21 case-control studies and three prospective cohort studies. The summary odds ratio (OR) and 95% confidence interval (CI) of all studies were acquired based on random effect model. Further subgroup analyses were conducted according to gender, histological type of thyroid cancer, and smoking status of patients for the case-control studies. RESULTS: The summary effect size indicated a negative association of smoking for thyroid cancer (OR, 0.798; 95% CI, 0.681 to 0.935). From the subgroup analyses for the case-control studies, reduced risk of thyroid cancer was observed in both men (OR, 0.734; 95% CI, 0.553 to 0.974) and women (OR, 0.792; 95% CI, 0.700 to 0.897). The protective effect of smoking was observed in studies in which thyroid cancer was limited to differentiated thyroid cancers (DTCs) (OR, 0.798; 95% CI, 0.706 to 0.902). CONCLUSION: Our results suggests that smoking may have a protective effect on thyroid cancer, especially on DTCs. Further studies with larger sample sizes should be conducted in elucidating the dose and time dependent effect of smoking on thyroid cancer with specific focus on the types of thyroid cancers.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol.

BACKGROUND: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. METHODS: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 µIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 µIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. CONCLUSION: The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

A national database analysis for factors associated with thyroid cancer occurrence.

In order to analyze the associations between thyroid cancer and environmental factors, we analyzed the national sample cohort representative of the entire population provided by the Korean National Health Insurance Service database record from 2006 to 2015. The cohort was categorized according to age, body mass index, income, residential areas, frequency of exercise, frequency of alcohol drinking, diet, presence or absence of hyperthyroidism, presence or absence of hypothyroidism, and smoking data. Age ≥ 55 years (HR 0.68, 95% CI 0.53-0.88), lower income (0.57, 0.40-0.80), and current smoking (0.69, 0.55-0.85) were associated with lower thyroid cancer occurrence among men. Body mass index (BMI) ≥ 25 kg/m2 (1.51, 1.26-1.82), higher income (1.44, 1.19-1.76), urban residence (1.24, 1.03-1.49), and presence of hypothyroidism (3.31, 2.38-4.61) or hyperthyroidism (2.46, 1.75-3.46) were associated with higher thyroid cancer occurrence among men. Age ≥ 55 years (0.63, 0.56-0.71), moderate alcohol drinking (0.87, 0.77-0.99), and current smoking (0.56, 0.37-0.85) were associated with lower thyroid cancer occurrence among women. BMI ≥ 25 kg/m2 (1.41, 1.26-1.57), frequent exercise (1.21, 1.07-1.36), higher income (1.18, 1.06-1.32), urban residence (1.17, 1.06-1.29), and presence of hypothyroidism (1.60, 1.40-1.82) or hyperthyroidism (1.38, 1.19-1.61) were associated with higher thyroid cancer occurrence among women. In conclusion, age ≥ 55 years and current smoking were associated with lower thyroid cancer occurrence, while BMI ≥ 25 kg/m2, higher income, urban residence, hypothyroidism, and hyperthyroidism were associated with higher occurrence in both men and women.

A Phase II Multi-Center, Non-Randomized, Parallel Group, Non-Inferiority Study to Compare the Efficacy of No Radioactive Iodine Remnant Ablation to Remnant Ablation Treatment in Low- to Intermediate-Risk of Papillary Thyroid Cancer: The MOREthyroid Trial Protocol.

BACKGROUND: Radioactive iodine (RAI) remnant ablation is recommended in patients with papillary thyroid cancer (PTC) and extrathyroidal extension or central lymph node metastasis. However, there exists little evidence about the necessity of remnant ablation in PTC patients with low- to intermediate-risk, those have been increasing in recent decades. METHODS: This multicenter, prospective, non-randomized, parallel group clinical trial will enroll 310 eligible patients with low- to intermediate-risk of thyroid cancer. Inclusion criteria are patients who recently underwent total thyroidectomy for PTC with 3 or less tumors of size 1≤ to ≤2 cm with no microscopic extension and N0/x, or size ≤2 cm with microscopic extension and/or N1a (number of lymph node ≤3, size of tumor foci ≤0.2 cm, and lymph node ratio <0.4). Patients choose to undergo RAI ablation (131I, dose 1.1 GBq) or diagnostic whole-body scan (DxWBS) (131I or 123I, dose 0.074 to 0.222 GBq), followed by subsequent measurement of stimulated thyroglobulin (sTg) within 1 year. Survey for quality of life (QOL) will be performed at baseline and at 1 year after follow-up. The total enrollment period is 5 years, and patients will be followed up for 1 year. The primary endpoint is the non-inferiority of surgery alone to surgery with ablation in terms of biochemical remission (BCR) rate (sTg ≤2 ng/mL) without evidence of structural recurrence. The secondary endpoint was the difference of QOL. CONCLUSION: This study will evaluate whether surgery alone achieves similar BCR and improved QOL compared to RAI ablation in patients with low- to intermediate-risk PTC within 1 year.

Functional Voice and Swallowing Outcome Analysis After Thyroid Lobectomy: Transoral Endoscopic Vestibular Versus Open Approach.

BACKGROUND: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a scarless remote-access thyroidectomy technique. This study compared subjective and objective voice outcomes and swallowing outcomes of patients who underwent thyroid lobectomy using the TOETVA versus conventional open thyroidectomy (OT). METHODS: In addition to questionnaires, acoustic and aerodynamic analyses were performed to compare subjective and objective voice outcomes of the two groups. Swallowing outcome analyses were conducted using Swallowing Impairment Index-6 (SIS-6) scores. Assessments were performed preoperatively and 3 and 6 months after surgery. Propensity score matching was performed to compare the outcomes of the two groups. RESULTS: One hundred and two patients were included in this study (52 TOETVA and 50 OT). Excluding two patients who had vocal cord palsy and open conversion in the TOETVA group, 100 patients completed 3-month postoperative surveys. There were no significant differences between the groups in VAS, GRBAS, or VHI-10 scores at the preoperative and 3- and 6-month assessments. For both groups, there were no significant changes in acoustic or aerodynamic parameters during the 3-6-month postoperative period. The TOETVA group had lower SIS-6 scores at the postoperative 6-month assessment, but the SIS-6 scores after 12 months were similar between groups before and after propensity score matching. CONCLUSIONS: Following TOETVA lobectomy, there were no significant changes in voice outcomes 3 and 6 months after surgery, and the outcomes were comparable with those of OT. The TOETVA group also had swallowing outcomes that were comparable with the OT group.

Feasibility of Attachable Ring Stimulator for Intraoperative Neuromonitoring during Thyroid Surgery.

OBJECTIVE: Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. METHODS: Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. RESULTS: Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 µV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 µV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 µV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 µV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. CONCLUSION: The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.

2019 Practice guidelines for thyroid core needle biopsy: a report of the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association.

Ultrasound-guided core needle biopsy (CNB) has been increasingly used for the pre-operative diagnosis of thyroid nodules. Since the Korean Society of the Thyroid Radiology published the 'Consensus Statement and Recommendations for Thyroid CNB' in 2017 and the Korean Endocrine Pathology Thyroid CNB Study Group published 'Pathology Reporting of Thyroid Core Needle Biopsy' in 2015, advances have occurred rapidly not only in the management guidelines for thyroid nodules but also in the diagnostic terminology and classification schemes. The Clinical Practice Guidelines Development Committee of the Korean Thyroid Association (KTA) reviewed publications on thyroid CNB from 1995 to September 2019 and updated the recommendations and statements for the diagnosis and management of thyroid nodules using CNB. Recommendations for the resolution of clinical controversies regarding the use of CNB were based on expert opinion. These practical guidelines include recommendations and statements regarding indications for CNB, patient preparation, CNB technique, biopsy-related complications, biopsy specimen preparation and processing, and pathology interpretation and reporting of thyroid CNB.

Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro).

Background: In this ongoing multicenter prospective cohort study on active surveillance (AS) in low-risk papillary thyroid microcarcinoma (PTMC), we aimed to compare the quality of life (QoL) of participants based on their choice of treatment, that is, AS or immediate surgery (OP). Methods: QoL of 203 participants who chose AS and 192 participants who underwent OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 8 months). Results: The mean ages of the participants in the AS and OP groups were 47.3 ± 11.7 and 45.6 ± 10.5 years (p = 0.138), respectively, and the mean tumor sizes were 5.7 ± 1.6 and 6.5 ± 2.1 mm (p = 0.065), respectively. At baseline, significantly better psychological health (7.1 ± 1.3 vs. 6.8 ± 1.6, p = 0.023) and overall health (6.8 ± 1.2 vs. 6.5 ± 1.3, p = 0.018) were observed in the AS group than in the OP group. During follow-up, significantly better physical (7.9 ± 1.1 vs. 7.4 ± 1.2, p < 0.001), psychological (7.4 ± 1.3 vs. 6.9 ± 1.6, p = 0.004), and overall health (6.9 ± 1.0 vs. 6.5 ± 1.1, p = 0.002) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups. Compared with the AS group, the OP group experienced more fatigue, changes in voice and appearance, less satisfaction, and low fear of recurrence. The self-assessed financial burden was similar at baseline and follow-up in both groups. Conclusion: The QoL of PTMC patients is different according to the type of treatment. Better psychological health at baseline and physical and psychological health at follow-up were observed in the AS group than in the OP group. However, studies with longer follow-up periods are needed.

Ultrasound image analysis using deep learning algorithm for the diagnosis of thyroid nodules.

Fine needle aspiration (FNA) is the procedure of choice for evaluating thyroid nodules. It is indicated for nodules >2 cm, even in cases of very low suspicion of malignancy. FNA has associated risks and expenses. In this study, we developed an image analysis model using a deep learning algorithm and evaluated if the algorithm could predict thyroid nodules with benign FNA results.Ultrasonographic images of thyroid nodules with cytologic or histologic results were retrospectively collected. For algorithm training, 1358 (670 benign, 688 malignant) thyroid nodule images were input into the Inception-V3 network model. The model was pretrained to classify nodules as benign or malignant using the ImageNet database. The diagnostic performance of the algorithm was tested with the prospectively collected internal (n = 55) and external test sets (n = 100).For the internal test set, 20 of the 21 FNA malignant nodules were correctly classified as malignant by the algorithm (sensitivity, 95.2%); and of the 22 nodules algorithm classified as benign, 21 were FNA benign (negative predictive value [NPV], 95.5%). For the external test set, 47 of the 50 FNA malignant nodules were correctly classified by the algorithm (sensitivity, 94.0%); and of the 31 nodules the algorithm classified as benign, 28 were FNA benign (NPV, 90.3%).The sensitivity and NPV of the deep learning algorithm shown in this study are promising. Artificial intelligence may assist clinicians to recognize nodules that are likely to be benign and avoid unnecessary FNA.

Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Korean Patients with Type 2 Diabetes Mellitus in Real-World Clinical Practice.

BACKGROUND: This study aimed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in Korean patients who had inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice. METHODS: We included 410 patients who started SGLT2 inhibitors (empagliflozin or dapagliflozin) as add-on therapy or switch therapy between February 2015 and June 2017. The primary efficacy endpoint was a change in glycosylated hemoglobin (HbA1c) from baseline to week 12. The secondary endpoints were patients achieving HbA1c <7.0% and changes in the fasting plasma glucose (FPG), lipid profiles, body weight, and blood pressure (BP). RESULTS: The mean HbA1c at baseline was 8.5% (8.6% in the add-on group and 8.4% in the switch group). At week 12, the mean adjusted HbA1c decreased by -0.68% in the overall patients (P<0.001), by -0.94% in the add-on group, and by -0.42% in the switch group. Significant reductions in FPG were also observed both in the add-on group and switch group (-30.3 and -19.8 mg/dL, respectively). Serum triglyceride (-16.5 mg/dL), body weight (-2.1 kg), systolic BP (-4.7 mm Hg), and diastolic BP (-1.3 mm Hg) were significantly improved in the overall patients. Approximately 18.3% of the patients achieved HbA1c <7.0% at week 12. A low incidence of hypoglycemia and genital tract infection was observed (6.3% and 2.2%, respectively). CONCLUSION: SGLT2 inhibitors can be a suitable option as either add-on or switch therapy for Korean patients with inadequately controlled T2DM.

Comprehensive Transcriptomic and Genomic Profiling of Subtypes of Follicular Variant of Papillary Thyroid Carcinoma.

BACKGROUND: Among subtypes of follicular variant of papillary thyroid carcinoma (FVPTC), encapsulated FVPTC (EFVPTC) shows more indolent behavior than infiltrative FVPTC (IFVPTC). In particular, noninvasive EFVPTC, now designated as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), tends to have an excellent prognosis. However, it remains unclear whether the molecular pathogenesis or signature of the various forms of FVPTC is different. By massively parallel sequencing analysis, this study comprehensively characterized the transcriptional and mutational landscape of FVPTC and established correlations with phenotypic subtypes. METHODS: This study included 48 FVPTCs: 17 NIFTPs, 13 invasive EFVPTCs (I-EFVPTCs), and 18 IFVPTCs. For comparison, 55 classical papillary thyroid carcinomas (cPTCs) harboring a BRAFV600E mutation, six follicular adenomas (FAs), and 15 minimally invasive follicular thyroid carcinomas (miFTCs) with RAS mutations were also included. RESULTS: In NIFTP, the BRAFV600E mutation was not found, but RAS and other alterations were present in 64.7% and 17.6% of cases, respectively. However, in I-EFVPTC and IFVPTC, the proportions of BRAFV600E mutation (38.5% and 38.9%, respectively) and of RAS mutations (38.5% and 38.9%, respectively) or other alterations (15.4% and 16.7%, respectively) were similar. On a molecular level, RAS-mutated FVPTCs were all RAS-like except for one IFVPTC case. Transcriptomic profiles of NIFTP, I-EFVPTC, and FA/miFTC were comparable, although the profile of RAS-mutated IFVPTC was altered to activate molecular pathways involved in cell adhesion and invasion. Interestingly, 80% of BRAFV600E-mutated I-EFVPTCs were also classified as RAS-like, whereas all BRAFV600E-mutated IFVPTCs were BRAF-like and indistinguishable from cPTC. Molecular pathways associated with cell adhesion and invasion were also differentially activated in BRAFV600E-mutated IFVPTC. CONCLUSIONS: Molecular profiles of NIFTP and I-EFVPTC may be shared with FA/miFTC, while IFVPTC seems to be associated with a similar profile as cPTC. Activation of cell adhesion and invasion pathways may play a key role in the development of invasive phenotypes of FVPTC.