Diagnostic performance of shear wave elastography in thyroid nodules with indeterminate cytology: A systematic review and meta-analysis.

Purpose: Thyroid nodules classified as indeterminate in previous fine-needle aspiration cytology often necessitate additional evaluation to determine their histology, while shear wave elastography (SWE) offers an alternative option in this regard. The objective of this study was to assess the diagnostic effectiveness of SWE in evaluating indeterminate nodules. Methods: The PubMed, EMBASE, and Web of Science databases were searched from 1st January 1970 to 1st March 2023. The studies were reviewed and the data was extracted by two separate reviewers. A Bayesian bivariate model was utilized to quantitatively synthesize the diagnostic accuracy and yield of the studies in R. Results: A total of seven studies, involving indeterminate thyroid nodules undergoing SWE were included, and the overall malignancy rate was 34.1% (307/900). The summarized estimates of sensitivity and specificity were 0.792 (95% credible interval [CI], 0.727-0.850) and 0.845 (95% CI, 0.797-0.887), respectively. The summarized estimate for the diagnostic odds ratio (DOR) was 17.8 (95% CI, 14.0-22.6). Summarized receiver operating characteristic (SROC) plots indicated a trade-off between sensitivity and specificity, and the estimate of AUC was 0.866 (95% CI, 0.834-0.895). The summary estimates for positive and negative likelihood ratios were 4.67 (95% CI, 3.98-5.85) and 0.26 (95% CI, 0.23-0.28), respectively. Conclusions: The overall accuracy of SWE remains satisfactory in indeterminate thyroid nodules. However, it should be noted that the available data are still extremely limited, and more studies or guidelines are required to provide further insights.

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms.

Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA's significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA's action represents a crucial research direction to pursue in the future.

Diagnostic performance of ultrasound risk stratification systems on thyroid nodules cytologically classified as indeterminate: a systematic review and meta-analysis.

PURPOSE: Ultrasound (US) risk stratification systems (RSSs) are increasingly being utilized for the optimal management of thyroid nodules, including those with indeterminate cytology. The goal of this study was to evaluate the category-based diagnostic performance of US RSSs in identifying malignancy in indeterminate nodules. METHODS: This systematic review and meta-analysis was registered on PROSPERO (CRD42021266195). PubMed, EMBASE, and Web of Science were searched through December 1, 2022. Original articles reporting data on the performance of US RSSs for indeterminate nodules were included. The numbers of nodules classified as true negative, true positive, false negative, and false positive were extracted. RESULTS: Thirty-three studies evaluating 7,225 indeterminate thyroid nodules were included. The diagnostic accuracy was quantitatively synthesized using a Bayesian bivariate model based on the integrated nested Laplace approximation in R. For the intermediate- to high-risk category, the sensitivity levels of the American College of Radiology, the American Thyroid Association, the European Thyroid Association, the Korean Thyroid Association/Korean Society of Thyroid Radiology, and Kwak et al. were found to be 0.80, 0.72, 0.76, 0.96, and 0.97, respectively. The corresponding specificity measurements were 0.36, 0.50, 0.49, 0.28, and 0.17. Furthermore, for the high-risk category, the sensitivity values were 0.40, 0.46, 0.55, 0.47, and 0.10, while the specificity levels were 0.91, 0.90, 0.71, 0.91, and 0.99, respectively. CONCLUSION: The overall diagnostic performance of the US RSSs was moderate in the differentiation of indeterminate nodules.

Diagnostic performance of adult-based ultrasound risk stratification systems in pediatric thyroid nodules: a systematic review and meta-analysis.

Purpose: Ultrasound (US) is the first choice in the detection of thyroid nodules in pediatric and adult patients. The purpose of this study was to evaluate the diagnostic performance of adult-based US risk stratification systems (RSSs) when applied to the pediatric population. Methods: Medline, Embase, and Cochrane Library (CENTRAL) were searched up to 5 March 2023 for studies about the diagnostic performance of adult-based US RSS in pediatric patients. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were also analyzed. Results: The sensitivity was highest in American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS) category 4-5 and American Thyroid Association RSS high-intermediate risk (ATA), which was 0.84 [0.79, 0.88] and 0.84 [0.75, 0.90], respectively. The specificity was highest in ACR-TIRADS category 5 and Europe-TIRADS (EU-TIRADS) category 5, which was 0.93 [0.83, 0.97] and 0.93 [0.88, 0.98], respectively. The ACR-TIRADS, ATA, and EU-TIRADS showed moderate diagnostic performance in pediatric thyroid nodule patients. For Korea-TIRADS (K-TRADS) category 5, the summary sensitivity and specificity with a 95% CI were 0.64 [0.40, 0.83] and 0.84 [0.38, 0.99], respectively. Conclusions: In conclusion, the ACR-TIRADS, ATA, and EU-TIRADS have moderate diagnostic performance in pediatric thyroid nodule patients. The diagnostic efficacy of the K-TIRADS was not as high as expected. However, the diagnostic performance of Kwak-TIRADS was uncertain because of the small sample size and small number of studies included. More studies are needed to evaluate these adult-based RSSs in pediatric patients with thyroid nodules. RSSs specific for pediatric thyroid nodules and thyroid malignancies were necessary.

A lightweight network for automatic thyroid nodules location and recognition with high speed and accuracy in ultrasound images.

BACKGROUND: The intelligent diagnosis of thyroid nodules in ultrasound image is an important research issue. Automatically locating the region of interest (ROI) of thyroid nodules and providing pre-diagnosis results can help doctors to diagnose faster and more accurate. OBJECTIVES: This study aims to propose a model, which can detect multiple nodules stably and accurately in order to avoid missed detection and misjudgment. In addition, the detection speed of the model needs to be fast for real-time diagnosis in ultrasound images. METHODS: Based on the object detection technology, we propose an accurate, robust and high-speed network with multiscale fusion strategy called Efficient-YOLO, which can realize the localization and recognition of nodules at the same time. Finally, multiple metrics are used to measure the diagnostic ability of the model. RESULTS: Experimental results conducted on 3,562 ultrasound images show that our new model greatly increases the accuracy and speed of the detection compared with the baseline model. The best mAP is 92.64%, and the fastest detection speed is 45.1 frames per second. CONCLUSIONS: This study proposed an effective method to diagnosis thyroid nodules automatically, which can meet the real-time requirements, indicating that its effectiveness and feasibility for future clinical application.

Diagnostic value of supersonic shear impulse elastography for malignant cervical lymph nodes: a Bayesian analysis.

PURPOSE: This study aimed to assess the diagnostic performance of supersonic impulse (SSI) elastography in differentiating malignant and benign cervical lymph nodes. METHODS: The Medline, Embase, and Cochrane Central databases were searched until December 1, 2020. Two different reviewers checked the studies and extracted the data. The diagnostic yields were quantitatively synthesized using a Bayesian bivariate model with an integrated nested Laplace approximation in R. RESULTS: In total, 590 patients with 892 cervical lymph nodes who underwent SSI elastography were included. The total prevalence of malignancy was 33.7% (301/892), and the four elastic modulus values (mean, maximum, minimum, and standard deviation) were significantly different between malignant and benign lymph nodes. For the mean elastic modulus, the summary estimates for sensitivity and specificity were 0.720 (95% credible interval [CrI], 0.592 to 0.824) and 0.877 (95% CrI, 0.727 to 0.969), respectively. The estimated area under the curve (AUC) was 0.845 (95% CrI, 0.672 to 0.914). For the maximum elastic modulus, the sensitivity and specificity were estimated to be 0.809 (95% CrI, 0.698 to 0.899) and 0.816 (95% CrI, 0.643 to 0.924), respectively. The estimated AUC was 0.834 (95% CrI, 0.579 to 0.938). The minimum and standard deviation of the elastic modulus and the outcomes of the positive and negative likelihood ratio, diagnostic odds ratio, and risk difference were also calculated. CONCLUSION: SSI elastography is an acceptable imaging technique for diagnosing malignant cervical lymph nodes, and it can play a complementary role today. Both maximum and mean elastic modulus values should be taken into consideration to make a clinical judgment.

Ultrasound-guided thermal ablation for cervical lymph node metastasis from thyroid carcinoma: a meta-analysis of clinical efficacy and safety.

To evaluate the efficacy and safety of thermal ablation (radiofrequency, microwave, and laser) for treating lymph node metastasis from papillary thyroid carcinoma. A literature search was performed in the Medline, Embase, and Cochrane Library databases. Thirteen studies focusing on the efficacy and safety of thermal ablation for treating lymph node metastasis were eligible. The assessed outcomes were primarily pooled using a random- or fixed-effects model based on the results of the heterogeneity test. A total of 235 patients with 445 metastatic lymph nodes were included. Laser, microwave, and radiofrequency ablation all showed a significant reduction in maximum diameter and volume of metastatic lymph nodes (P < 0.0001). Microwave ablation had a higher volume reduction rate (99%; 95% CI, 98-100%) comparing to the other two techniques (P = 0.0057). For all ablations, the pooled completely disappear rate was 70% (95% CI, 45-87%) and the recurrent rate was 3% (95% CI, 2-5%). Thyroglobulin levels significantly decreased (P < 0.0001). No major complications were encountered; the pooled proportion of voice change was low to 4% (95% CI, 2-7%). Thermal ablation is acceptable treatments to manage lymph nodes metastasis from papillary thyroid carcinoma in terms of efficacy and safety for non-surgical candidates.

Does the number of autotransplanted parathyroid glands affect postoperative hypoparathyroidism and serum parathyroid hormone levels?

BACKGROUND: To investigate how number of autotransplanted parathyroid glands (PGs) affects the incidence of postoperative hypoparathyroidism and the recovery of parathyroid function. METHODS: A systematic search was performed in the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. The evaluated indices included the incidence of postoperative transient and permanent hypoparathyroidism and parathyroid hormone (PTH) levels during follow-up. RESULTS: Twenty articles with 7291 patients were included. A higher incidence of transient hypoparathyroidism was found in the PG autotransplantation group than in the preservation group (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.90, 2.96). However, there was no significant difference between the two groups regarding permanent hypoparathyroidism (OR: 1.17; 95% CI: 0.71, 1.91). Parathyroid hormone (PTH) levels in the PG autotransplantation group changed significantly more than the preservation group at postoperative 1-day and 1-month, but became similar at the 6-month, 1-year and 2-year follow-up. Autotransplantation of 2 and 3 PGs demonstrated a higher incidence of transient hypoparathyroidism than 1 PG (OR: 2.09; 95% CI: 1.41, 3.11 and OR: 9.70; 95% CI: 2.11, 44.39, respectively), but no significant difference was observed between the autotransplantation of 3 and 2 PGs (OR: 0.99; 95% CI: 0.03, 29.06). Additionally, the incidence of permanent hypoparathyroidism was not significantly different when different number of PGs was autotransplanted. CONCLUSIONS: PG autotransplantation is an effective mid- and long-term strategy for the preservation of parathyroid function. Although transient hypoparathyroidism was positively correlated with the number of autotransplanted PGs, no remarkable correlation was observed for permanent hypoparathyroidism.

miR-148-3p inhibits gastric cancer cell malignant phenotypes and chemotherapy resistance by targeting Bcl2.

Gastric cancer(GC) is the fourth most common cancer in the world. This work was designed to explore the biological effects of miR-148-3p on GC. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized to analyze the mRNA expression of miR-148-3p in GC cell lines. The mimics and inhibitors of miR-148-3p, was carefully transfected into GC cells to up-regulate or down-regulate miR-148-3p expression. Observe the effect on miR-148-3p expression change to GC cell proliferation, colony formation, tumorigenesis, chemotherapy sensitivity, trans-well migration and invasion. Use online database tool to predict the miR-148-3p promising targets, and be verified via RT-qPCR, Western blot and luciferase report. We found that miR-148-3p expression level in GC cells was markedly down-regulated (P <0.05), as compared with human normal gastric mucosal cells GES-1. Otherwise, miR-148-3p overexpression could effectively inhibit the cell proliferation, cell cycle progress, colony formation, anti-apoptosis, anti-migration and anti-invasion in gastric cancer cells, whereas miR-148-3p inhibition exhibited the opposite phenomenon (P<0.05). Further research revealed that Bcl2 set as a direct downstream target of miR-148-3p. Our study firstly confirmed that, miR-148-3p might play a crucial role in tumorigenesis, as well as development of gastric cancer by targeting Bcl2, and could become a promising target for gastric cancer treatment.

Role of the 2018 American Thyroid Association statement on postoperative hypoparathyroidism: a 5-year retrospective study.

BACKGROUND: Definitions of postoperative hypoparathyroidism (hypoPT) have never reached consent until the American Thyroid Association (ATA) statement was released, with new characteristics and challenges. METHODS: Patients with papillary thyroid carcinoma who underwent primary total thyroidectomy between January 2013 and June 2018 were retrospectively enrolled. Symptoms of hypocalcemia and their frequency were stringently followed. Patients were divided into groups according to the ATA statement. Incidence of postoperative hypoPT and serum parathyroid hormone levels accompanied by calcium levels, from 1-day to at least 24-month follow-up. RESULTS: A total of 1749 patients were included: 458 (26.2%) had transient and 63 (3.6%) had permanent hypoPT. Transient hypoPT was found in 363 (20.7%) patients with biochemical hypoPT, 72 (4.1%) with clinical hypoPT, and 23 (1.3%) with relative hypoPT; permanent hypoPT was detected in 8 (0.5%) patients with biochemical hypoPT, 55 (3.1%) with clinical hypoPT, and none with relative hypoPT. Female sex, age ≥ 55 years, unintentional parathyroid gland resection, and autotransplantation of ≥ 2 parathyroid glands were independent risk factors for transient biochemical hypoPT. Age ≥ 55 years, bilateral central neck dissection, and isthmus tumor location were independent risk factors for transient clinical hypoPT. A postoperative 1-day percentage of parathyroid hormone (PTH) reduction of > 51.1% was an independent risk factor for relative hypoPT (odds ratio, 4.892; 95% confidence interval, 1.653-14.480; P = 0.004). No independent risk factor for permanent hypoPT was found. CONCLUSION: ATA diagnostic criteria for postoperative hypoPT are of great value in differentiating patients by hypocalcemia symptoms and choosing corresponding clinical assistance; however, they may underestimate the actual incidence.

Selective Parathyroid Autotransplantation During Total Thyroidectomy for Papillary Thyroid Carcinoma: A Cohort Study.

Purpose: The relationship between the selective parathyroid gland (PG) autotransplantation and hypoparathyroidism is still not completely clear. The aim was to ascertain whether the number of autotransplanted PGs affected the incidence of hypoparathyroidism and recovery of parathyroid function in the long-term for patients with papillary thyroid carcinoma (PTC). Methods: A retrospective cohort study included all patients with PTC who had underwent primary total thyroidectomy with central neck dissection between January 2013 and December 2017. The patients were divided into three groups (0, 1, and 2 PGs autotransplanted, respectively). Results: Of the 2,477 patients, 634 (25.6%) received no PG autotransplantation, 1,078 (43.5%) and 765 (30.9%) were autotransplanted 1 and 2 PGs, respectively, and the incidence of permanent hypoparathyroidism (>1 year) was 1.7%, 0.7%, and 0.4% (P = 0.0228). Both 1 or 2 PGs autotransplanted increased the incidence of transient biochemical hypoparathyroidism (odds ratio [OR], 1.567; 95% confidence interval [CI], 1.258-1.953; P < 0.0001; OR, 2.983; 95% CI, 2.336-3.810; P < 0.0001, respectively) but reduced the incidence of permanent hypoparathyroidism (OR, 0.373; 95% CI, 0.145-0.958; P = 0.0404; OR, 0.144; 95% CI, 0.037-0.560; P = 0.0052, respectively). Both 1 or 2 PGs autotransplanted did not independently influence the occurrence of hypocalcemia symptoms. Conclusion: Selective parathyroid autotransplantation is less likely to lead to post-operative symptomatic hypocalcemia, although it could lead to a transient decrease in parathyroid hormone. However, in the long run, it is still an effective strategy to preserve parathyroid function.

Birth control pills and risk of hypothyroidism: a cross-sectional study of the National Health and Nutrition Examination Survey, 2007-2012.

OBJECTIVE: The association between use of birth control pills and thyroid function in women has not ever been well studied, but potential risk has been implicated by small sample-sized studies. We aimed to determine this association using a large epidemiological survey. DESIGN: Cross-sectional study. SETTING: National Health and Nutrition Examination Survey conducted in the USA from 2007 to 2012. PARTICIPANTS: Female respondents aged 18+ who had data on history of taking birth control pills and thyroid function were included. History of taking birth control pills was based on responses on the reproductive health questionnaire. Participants not on antithyroid medication with thyroid-stimulating hormone (TSH) >5.6 mIU/L and those on thyroid hormone replacement regardless of TSH were categorised as hypothyroid. Participants not on thyroid hormone replacement or antithyroid medication who had TSH between 0.34 mIU/L and 5.6 mIU/L were classified as euthyroid. PRIMARY AND SECONDARY OUTCOME MEASURES: Association between use of birth control pills and hypothyroidism based on multivariate logistic regression analysis. RESULTS: A total of 5116 female adults with history of taking birth control pills (n=3034) and without (n=2082) were included. A higher prevalence of hypothyroidism was found in those who have ever taken birth control pills (17.7% vs 14.1%; p=0.003). Multivariate logistic regression adjusted for confounding covariables, including age, race, education, body mass index, smoking status, alcohol use, history of thyroid disease, current thyroid disease, first menstrual age, pregnancy history, menopause status and history of hormone replacement use, demonstrated a significant association between history of taking birth control pills for more than 10 years and hypothyroidism (OR, 3.837; 95% CI 1.402 to 10.500; p=0.009). CONCLUSIONS: Longer history of using birth control pills was strongly associated with hypothyroidism, especially for more than 10 years.

Duration of Parathyroid Function Recovery in Patients With Protracted Hypoparathyroidism After Total Thyroidectomy for Papillary Thyroid Carcinoma.

Purpose: The aim of the present study is to investigate the time to recovery of parathyroid function in patients with protracted hypoparathyroidism at 1 month after total thyroidectomy of papillary thyroid carcinoma. Materials and Methods: Adult patients who underwent total thyroidectomy for papillary thyroid cancer were included. Cases of long-term hypoparathyroidism were studied for recovery of parathyroid function during the follow-up. The duration of recovery and associated variables were recorded. Results: Out of the 964 patients, 128 (13.28%) developed protracted hypoparathyroidism and of these, 23 (2.39%) developed permanent hypoparathyroidism and 105 (10.89%) recovered: 86 (8.92%) before 6 months, 11 (1.14%) within 6 and 12 months and 8 (0.83%) after 1 year follow-up. Variables significantly associated with the time to parathyroid function recovery were number of autotransplanted parathyroid glands (HR, 1.399; 95% CI, 1.060 - 1.846; P = 0.018), serum calcium concentration >2.07 mmol/L (Hazard ratio [HR], 1.628; 95% confidence interval [CI], 1.009 - 2.628; P = 0.046) and PTH level > 1.2 pmol/L (HR, 1.702; 95% CI, 1.083 - 2.628; P = 0.021) at 1 month postoperatively. Conclusion: Permanent hypoparathyroidism should not be diagnosed easily by time, since up to one-fifth of the patients will experience recovery after a period of 6 months and a few patients even beyond one year. The number of autotransplanted parathyroid glands is positively associated with the time to parathyroid function recovery.

Surgical outcomes of different approaches in robotic assisted thyroidectomy for thyroid cancer: A systematic review and Bayesian network meta-analysis.

BACKGROUND: The aim of the study was to assess the feasibility, safety, and potential benefits of four approaches of robotic assisted thyroidectomy (RT). The approaches mentioned above are also compared with traditional open thyroidectomy (OPEN). MATERIALS AND METHODS: Medline, Embase, Cochrane library (CENTRAL) and Web of Science databases were searched up to 13th Dec 2019. Data of surgical outcomes and complications were extracted to conduct the statistical analyses. RESULTS: A total of 30 studies with 6622 patients were included. Ten were prospective study and 1 declared prospective randomized comparative study. The number of retrieved lymph nodes (LNs) in central compartment were similar between gasless transaxillary approach (GAA), bilateral axillo-breast approach (BABA) and transoral approach (OA). OPEN retrieved more LNs than BABA and OA. More metastatic LNs were seen in GAA and BABA than OA, as was for OPEN. The operation time was significantly shorter in GAA and gasless unilateral transaxillary approach (GUAA) than BABA and OA, while shortest for OPEN. Lower incidence of transient hypoparathyroidism was found in BABA than OPEN. No significant difference was observed in other indexes. CONCLUSIONS: BABA, GAA, GUAA and OA in RT appear to be feasible and safe for patients with thyroid cancer with unique benefits. Surgical outcomes of different approaches were not identical for operation time, cosmetic effects, central neck dissection. Surgeons would consider more about patients' will.

Protective strategy of parathyroid glands during thyroid lobectomy: A retrospective cohort and case-control study.

ABSTRACT: Parathyroid protection during thyroid lobectomy was not illustrated previously. Aim of this study was to find out the influence of parathyroid glands in situ preservation and autotransplantation on postoperative parathyroid function in thyroid lobectomy.Consecutive patients who underwent primary thyroid lobectomy with unilateral central neck dissection for papillary thyroid carcinoma in our center were included retrospectively. Postoperative hypoparathyroidism was defined as low parathyroid hormone (PTH) levels (<1.6 pmol/L) and keeping over 6 months was defined as permanent. Patients were divided into 3 groups: all identified parathyroid glands preserved in situ (preservation group); at least one parathyroid gland autotransplanted without accidental resection (autotransplantation group); at least one parathyroid gland accidental resected (resection group).A total of 425 patients were included. No permanent hypoparathyroidism was reported, and the rates of transient hypoparathyroidism were similar among all groups. Significantly lower serum PTH levels were found in autotransplantation group versus preservation group at postoperative 1-day (3.77 ±â€Š1.61 vs 4.72 ±â€Š2.31, P < .001). Transient hypoparathyroidism was significantly associated with reduced intraoperative carbon nanoparticles utilization (57.1% vs 77.4%, P = .039).Thyroid lobectomy was a safe surgical method for parathyroid protection no matter the practice to ipsilateral parathyroid glands. However, preservation of all parathyroid glands was still recommended considering relatively stable PTH levels.

Insufficient evidence to support the clinical efficacy of selenium supplementation for patients with chronic autoimmune thyroiditis.

BACKGROUND: This study critically reappraises the documentation on the clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis (AIT) with the goal of improving the normalization of the treatment of this disease. METHODS: A literature search was performed in the Medline, Embase, and Cochrane Library databases. Twenty-three trials conducted in adults with AIT comparing the efficacy of selenium with or without levothyroxine (LT4) versus placebo and/or LT4 were eligible. The assessed outcomes were primarily pooled using a random- or fixed effects model based on the results of the heterogeneity test. The quality of evidence was assessed per outcome. RESULTS: In LT4-treated populations, patients receiving selenium demonstrated lower thyroid peroxidase antibody (TPOAb) levels at 3 months (mean difference [MD], -236.88; 95% confidence interval [CI], -353.35 to -120.41; p < 0.0001), 6 months (MD, -407.17; 95% CI, -623.60 to -190.73; p = 0.0002), and 12 months (MD, -327.03; 95% CI, -613.78 to -40.28; p = 0.0254), while thyroglobulin antibody (TgAb) levels only decreased at 12 months. In non-LT4-treated population, the selenium group demonstrated significantly lower TPOAb levels after 3 months (MD, -203.07; 95% CI, -395.44 to -10.70; p = 0.0385) and 6 months (MD, -322.27; 95% CI, -597.50 to -47.04; p = 0.0217) but not after 12 months, while TgAb levels only decreased at 3 months. There was no significant change in thyroid stimulating hormone (TSH) levels. Lower thyroid echogenicity was observed in all patients receiving selenium at 3, 6, and 12 months. However, these participants had a significantly higher risk of reported adverse effects. CONCLUSIONS: Current evidence does not justify the emerging use of selenium supplementation in the treatment of AIT, despite it resulting in a decrease in autoantibody levels.

Surgical strategy when identifying less than four parathyroid glands during total thyroidectomy: a retrospective cohort study.

BACKGROUND: Parathyroid glands protection is still controversial in patients with less than 4 parathyroid glands during thyroidectomy. The aim of this study was to investigate the strategy of parathyroid autotransplantation or in situ preservation in patients with 3 parathyroid glands. METHODS: Consecutive patients who underwent primary total thyroidectomy with bilateral central neck dissection for papillary thyroid carcinoma (PTC) in our center were included retrospectively. Serum calcium and parathyroid hormone (PTH) levels (pg/mL), incidence of hypocalcemia and hypoparathyroidism during 24 months follow-up were compared grouping by the number of parathyroid glands both identified intraoperatively and confirmed postoperatively by pathology. RESULTS: A total of 1,424 patients were included. Serum PTH and calcium levels were lower and the incidence of hypocalcemia was higher in patients with 3 identified parathyroid glands. When excluding patients with accidental parathyroid resection, the results remained similar. Of the 212 patients with 3 identified parathyroid glands, PTH levels at postoperative 12-month in patients underwent autotransplantation were significantly lower than patients with all parathyroid glands preserved in situ (3.65±1.30 vs. 4.67±1.89, P=0.026). CONCLUSIONS: The parathyroid function was weaker in patients with 3 parathyroid glands than patients with 4 before and after operation. Parathyroid glands preserved all in situ promoted better recovery of postoperative function in patients with 3 identified parathyroid glands.

Structure-based optimization identified novel furyl-containing 2,4-diarylaminopyrimidine analogues as ALK/ROS1 dual inhibitors with anti-mutation effects.

Aiming to develop ALK/ROS1 dual inhibitors overcoming ceritinib-resistant G1202R mutant, a dedicated structure-guided modification campaign was conducted based on ALK co-crystal structures. Twenty eight diarylaminopyrimidine (DAAP) analogues possessing furan or tetrahydrofuran group were designed and synthesized, among which compound 16 bearing (dimethylamino)methyl)furan-2-yl)methyl)thio fragment was identified. Compound 16 exhibited significant cytotoxicity on ALK-positive Karpas299 and H2228 cells with IC50 values of 20 nM and 110 nM. Meanwhile, compound 16 turned out as the most potent entity superior to ceritinib with IC50 values of 2.8, 2.6, 3.8 and 2.3 nM against ALKWT, ALKL1196M, ALKG1202R and ROS1WT, respectively. Subsequently, western blot assay showed that compound 16 significantly suppressed ALK and its downstream protein expression in a dose-dependent manner. Alternatively, the Hoechst 33258 and AO/EB staining assays illustrated that compound 16 could induce H2228 cell apoptosis. Ultimately, the binding models of compound 16 with ALKWT, ALKG1202R as well as ROS1 clearly presented the essential interactions within the active site. Together, compound 16 was validated as a promising ALK/ROS1 dual inhibitor for ALKG1202R mutation correlated tumors.

Predictors of thyroglobulin in the lymph nodes recurrence of papillary thyroid carcinoma undergoing total thyroidectomy.

BACKGROUND: To investigate the association between postoperative lymph nodes (LNs) recurrence and distinct serum thyroglobulin (Tg) levels in patients with papillary thyroid carcinoma (PTC). METHODS: This study included PTC patients who underwent total thyroidectomy (TT) with at least central neck dissection and then re-operated due to recurrence of LNs between January 2013 and June 2018. These patients were grouped by negative or positive serum Tg levels according to the American Thyroid Association guidelines. RESULTS: Of the 60 included patients, 49 underwent radioactive iodine (RAI) treatment. Maximum unstimulated Tg (uTg) ≥ 0.2 ng/mL were associated with larger diameter of recurrent LNs (P = 0.027), and higher rate of metastatic LNs (P < 0.001). Serum-stimulated Tg (off-Tg) ≥ 1 ng/mL (P = 0.047) and unstimulated Tg (on-Tg) ≥ 0.2 ng/Ml (P = 0.013) were associated with larger diameter of recurrent LNs. Number of metastatic LNs ≥ 8 was an independent predictor for postoperative maximum uTg ≥ 0.2 ng/mL (OR = 8.767; 95% CI = 1.392-55.216; P = 0.021). Ratio of metastatic LNs ≥ 25% was an independent predictor for off-Tg ≥ 1 ng/mL (OR = 20.997; 95% CI = 1.649-267.384; P = 0.019). CONCLUSION: Postoperative Tg-positive status was associated with larger size of recurrent LNs. Number of metastatic LNs ≥ 8 and ratio of metastatic LNs ≥ 25% were independent predicators for uTg-positive and off-Tg-positive status, respectively.