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Background: Limited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC)., Methods: In this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more., Results: In our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest., Conclusions: In long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Lv, Liu, Zheng, Zhang, Dong and Zhang.)

Background: Observational studies have reported a possible association between metabolic syndrome (MetS) and thyroid autoimmunity. Nevertheless, the relationship between thyroid autoimmunity and MetS remains unclear. The objective of this research was to assess the causal impact of MetS on thyroid autoimmunity through the utilization of Mendelian randomization (MR) methodology., Methods: We performed bidirectional MR to elucidate the causal relationship between MetS and their components and thyroid autoimmunity (positivity of TPOAb). Single nucleotide polymorphisms (SNPs) of MetS and its components were obtained from the publicly available genetic variation summary database. The Thyroidomics Consortium conducted a genome-wide association analysis, which provided summary-level data pertaining to thyroid autoimmunity. The study included several statistical methods, including the inverse variance weighting method (IVW), weighted median, simple mode, weight mode, and MR-Egger methods, to assess the causal link. In addition, to ensure the stability of the results, a sensitivity analysis was conducted., Results: IVW showed that MetS reduced the risk of developing thyroid autoimmunity (OR = 0.717, 95% CI = 0.584 - 0.88, P = 1.48E-03). The investigation into the causative association between components of MetS and thyroid autoimmune revealed a statistically significant link between triglycerides levels and the presence of thyroid autoimmunity (IVW analysis, OR = 0.603, 95%CI = 0.45 -0.807, P = 6.82E-04). The reverse analysis did not reveal any causal relationship between thyroid autoimmunity and MetS, including its five components., Conclusions: We have presented new genetic evidence demonstrating that MetS and its triglyceride components may serve as potential protective factors against thyroid autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Sun, He, Dong, Zhang, Zhang and Zhang.)

Introduction: Identifying risk variables for cervical lymph node metastases in multifocality papillary thyroid cancer (MPTC) could assist surgeons in determining whether cervical lymph node dissection would be an appropriate surgical option., Methods: A retrospective cohort of 2006 patients with papillary thyroid cancer were selected. MPTC (N = 460) was defined as the presence of two or more foci of PTC. The risk factors for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) in MPTC were investigated by univariate and multivariate analyses, including the following items: age at diagnosis, gender, Hashimoto's thyroiditis, extrathyroidal extension (ETE), maximal axial diameter (MAD) and the sum of axial diameters (SAD) of tumor. In addition, CLNM was used to evaluate LLNM., Results: The incidence of CLNM and LLNM was 44.57% and 17.17%, respectively. The multivariate analysis demonstrated that gender, extrathyroidal extension (ETE), age, maximal axial diameter (MAD), and the sum of axial diameters (SAD) were related to increased risk for CLNM in MPTC ( p < 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) for age at diagnosis of CLNM was 0.647, the cut-off value was 50 years old. Additionally, by multivariate analysis, CLNM, ETE, MAD, and SAD were independent risk factors for LLNM in MPTC ( p < 0.05). ROC curve analysis demonstrates that AUC for MAD and SAD diagnosis of LLNM were 0.639 and 0.757, and the cut-off values were 16 and 26 mm, respectively., Conclusions: MPTC patients who have risk factors for CLNM were advised to perform prophylactic central lymph node dissection (CLND). Additionally, the presence of risk factors for LLNM should be individually evaluated and analyzed for the necessity of lateral lymph node dissection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, He, Wang, Dong, Sun, Zhang and Zhang.)

Objective: Children with papillary thyroid cancer (PTC) have a higher invasive rate and distant metastasis rate, but the mortality rate is lower with unknown reasons. The majority of PTC cases comprise classical papillary thyroid carcinoma (CPTC) and follicular variant papillary thyroid carcinoma (FVPTC). This study aimed to determine the relationship between histopathological subtype and rate of distant metastasis and investigate factors influencing distant metastasis in pediatric PTC., Methods: A total of 102,981 PTC patients were recruited from SEER registry, 2004-2015. Proportion of distant metastasis between children (≤18 years) and adults with different histopathological subtypes was compared by propensity score matching. The cut-off age for distant metastasis in children was calculated by receiver operating characteristic (ROC) curve, and the risk factors for distant metastasis in pediatric patients were analyzed by logistic regression models., Results: Among the 1,484 children and 101,497 adults included in the study, the incidence of CPTC patients with distant metastasis in children was higher than that in adults ( p <0.001). The ROC curve was calculated, which yielded a cut-off age for distant metastasis in CPTC children as 16 years old. In CPTC, the proportion of young children (2-16 years) with distant metastasis was higher than that of adolescents (17-18 years) and adults (>18 years) (both p <0.001). While there was no such trend in FVPTC. In young children (2-16 years), the incidence of CPTC with distant metastasis was higher than FVPTC ( p =0.006). There was no difference between the proportion of CPTC and FVPTC with distant metastasis in adolescents (17-18 years) and adults. Logistic regression models revealed that extrathyroidal extension, lymph node metastasis and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2 -16 years., Conclusions: In CPTC, the incidence of distant metastasis in young children (2-16 years) was significantly higher than that in adolescents (17-18 years) and adults (>18 years). In patients with distant metastasis aged 2-16 years, the proportion of CPTC was higer than that of FVPTC. Extrathyroidal extension, lymph node metastasis, and CPTC histopathological subtype were risk factors for distant metastasis in young children aged 2-16 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zeng, Wang, Gui, Xiang, Cao, Sun, He, Dong, Huang, Zhang, Lv, Zhang, Shao, Zhang and Zhang.)

Background: As many inconsistent reports on the clinical manifestations and prognosis between unilateral unifocal PTC (UUPTC) and unilateral multifocal PTC (UMPTC), identifying the difference should guide management. The purpose of this study was to investigate other additional differences between UUPTC and UMPTC in addition to their difference in the number of cancer foci., Data Sources: A systematic literature search was conducted in the PubMed and Web of Science databases for relevant studies published before December 31, 2020. Their reference lists were also reviewed., Review Methods: Two reviewers independently extracted data and assessed the quality of eligible studies. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included. Data were analyzed using the RevMan 5.3 software., Results: Fifteen studies comprising 9,665 patients were selected for the meta-analysis. UMPTC occurred in 10% to 36% of all PTC cases. There were no significant differences between UMPTC and UUPTC patients in age, gender, tumor size, and extrathyroidal extension (ETE). However, significant differences (P < 0.05) between UMPTC and UUPTC patients were observed in central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), tumor-node-metastasis (TNM) stage I+II, TNM stage III+IV, the recurrence/persistence of the UMPTC group after total thyroidectomy and overall recurrence/persistence., Conclusion: UMPTC patients are more likely to have CLNM, LLNM, more advanced TNM stage, and recurrence/persistence than UUPTC patients. Compared with UUPTC, UMPTC patients should undergo central lymph node dissection, and pay more attention to LLNM, TNM stage and recurrence/persistence during the follow-up., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, He, Wang, Dong, Sun, Zhang and Zhang.)

NEAT1 (nuclear paraspeckle assembly transcript 1) is an oncogenic long non-coding RNA (lncRNA) that facilitates tumorigenesis in multiple cancers. In papillary thyroid cancer (PTC), the molecular mechanism by which NEAT1 affects invasion and metastasis remains elusive. RNA sequencing was used to discover differentially expressed NEAT1&#95;2 downstream genes. Protein and RNA expression analyses and immunohistochemistry detected the expression of NEAT1&#95;2 , Transglutaminase 2 (TGM2), and microRNA-491 (miR-491) among PTC and non-cancerous tissues. Transwell and wound healing assays, and a mouse model of lung metastasis were used for further functional analyses. Bioinformatics was performed to predict miRNAs binding to both NEAT1&#95;2 and TGM2 . Rescue experiments and dual-luciferase reporter assays were performed. In PTC tissues, NEAT1&#95;2 expression was markedly increased and regulated TGM2 expression. TGM2 was overexpressed in PTC, correlating positively with exthyroidal extension and lymph node metastasis. TGM2 knockdown significantly inhibited invasion and metastasis. NEAT1&#95;2 sponged miR-491, acting as a competing endogenous RNA to regulate TGM2 expression. Fibronectin 1 (FN1) was predicted as a TGM2 target. TGM2 could transcriptionally activate FN1 by promoting nuclear factor kappa B (NFκb) p65 nuclear translocation, ultimately promoting PTC invasion/metastasis. These findings identify that NEAT1&#95;2 sponges miR-491 to regulate TGM2 expression. TGM2 activates FN1 via NFκb to promote PTC invasion and metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sun, Qin, Wang, Dong, He, Zhang and Zhang.)

Background: As hypocalcemia is the most common complication of total thyroidectomy, identifying its risk factors should guide prevention and management. The purpose of this study was to determine the risk factors for postthyroidectomy hypocalcemia., Methods: We searched PubMed, Web of Science and EMBASE through January 31, 2019, and assessed study quality using the Newcastle-Ottawa Scale., Results: Fifty studies with 22,940 patients met the inclusion criteria, of which 24.92% (5716/22,940) had transient hypocalcemia and 1.96% (232/11,808) had permanent hypocalcemia. Significant ( P < 0.05) predictors of transient hypocalcemia were: younger age, female, parathyroid autotransplantation (PA), inadvertent parathyroid excision (IPE), Graves' disease (GD), thyroid cancer, central lymph node dissection, preoperative severe Vitamin D deficiency, preoperative Vitamin D deficiency and a lower postoperative 24 h parathyroid hormone (PTH) level. Preoperative magnesium, preoperative PTH and Hashimoto's thyroiditis were not significant predictors of transient hypocalcemia. IPE, GD, and thyroid cancer were associated with an increased rate of permanent hypocalcemia, but gender and PA did not predict permanent hypocalcemia., Conclusion: Important risk factors for transient and permanent hypocalcemia were identified. However, given the limited sample size and heterogeneity of this meta-analysis, further studies are required to confirm our preliminary findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Qin, Sun, Wang, Dong, He, Zhang and Zhang.)