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Persistence of thyroglobulin antibody (TgAb) in patients with papillary thyroid carcinoma (PTC) years after total thyroidectomy (TT) followed by ablation occurs even without any evidence of structural disease. Few studies have studied the natural course of TgAb positivity and factors that may influence this course. The present study evaluated the time trends of TgAb in ablated PTC patients and aimed to identify the predictive factors for the rate of negative conversion of TgAb.Overall, 1279 patients who underwent TT and subsequent ablation for PTC, with available data on thyroid peroxidase Ab (TPOAb) and TgAb prior to surgery (preop-) and ablation (abl-) were enrolled. Patients with initial distant metastasis or recurrence during follow-up were excluded.Preop-TgAb was positive in 24.9% of patients (n = 319), whereas abl-TgAb positivity decreased to 12.8% (n = 164). In 164 patients positive for abl-TgAb, TgAb in patients with higher abl-TgAb levels decreased more gradually than those observed in patients with lower abl-TgAb levels (p 0.001). Furthermore, in patients within the same range of abl-TgAb levels, patients positive for abl-TPOAb had a higher rate of negative conversion of TgAb compared with negative patients for abl-TPOAb (log rank p 0.001). TPOAb significantly increased the rate of negative conversion in multivariate analysis adjusted for abl-TgAb (odds ratio 1.59, 95% confidence interval 1.11-2.28, p = 0.011). This study clearly showed that abl-TgAb titers and abl-TPOAb status can predict the rate of negative conversion. These findings can guide the optimal timing for additional examination in patients positive for TgAb during follow-up.

Slits, representative axon guidance molecules, and their Roundabout (Robo) transmembrane receptors play roles in the progression of many cancers. We investigated the effects of Slit2 on the proliferation, migration, and invasion of thyroid cancer cells, and on the prognosis of papillary thyroid cancer (PTC). Slit2 overexpression inhibited the proliferation, migration and invasion of thyroid cancer cells by inhibiting transcriptional activity of beta-catenin and regulating Rho GTPase activity. Slit2 knockdown activated the migration and invasion of thyroid cancer cells and transcriptional activity of beta-catenin. Fragment Slit2 treatment inhibited thyroid cancer cell proliferation in a dose dependent manner, and also inhibited migration and invasion. When we evaluated the protein expression of Slit2 in PTCs, 24 of 160 PTCs (15%) were negative for Slit2 protein expression and these patients had significantly increased risk of cervical lymph node metastasis (P 0.001), distant metastasis (P 0.001) and recurrence of PTC (P 0.001). Our findings suggest a role for Slit2 as a tumor suppressor, and also as a novel prognostic and potential therapeutic target for thyroid cancer.

Patients with differentiated thyroid carcinoma (DTC) are staged according to the single age cut point in addition to anatomic extent. A novel staging system is needed to properly show the character and prognosis of DTC by considering age as a continuous variable. We aimed to refine stage and prognostic groups of the eighth edition tumor-node-metastasis (TNM-8) staging system for DTC and to suggest a possible revision.We conducted a retrospective data abstraction study of patients with newly diagnosed DTC who were treated at one of two tertiary referral centres in Seoul, Korea between 1994 and 2005. We used recursive partitioning analysis to derive a new staging classification (TNM-RPA) and compared its prediction of cancer-specific survival with that of TNM-8.The cohort comprised 6342 patients with DTC who were followed up for a median of 11.4 years. Higher TNM-RPA groups were associated with increased risk of death (10-year cancer-specific survival for stages IA, IB, IIA, IIB, III, and IV: 99.6%, 98.1%, 93.0%, 92.4%, 75.1%, and 56.6%, respectively; P 0.001). The C-index values were 0.869 (95% CI, 0.833-0.905) for the TNM-RPA and 0.819 (0.789-0.850) for TNM-8. The proportions of variance explained for the ability of the TNM-RPA and TNM-8 stages to predict cancer-specific survival were 7.1% and 5.7%, respectively.This study presents a RPA-based TNM stage groupings that incorporate multiple age cutoffs and essential anatomic information, which can be conveniently used to facilitate the individual prediction of long-term cancer-specific survival in patients with DTC.

Objectives This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort. Materials and methods We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS). Results During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group. Conclusion Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Background: Tendons have limited reparative ability. With less specialized tissue characteristics, tendon injury might be one of the most promising tissues to be successfully treated by stem cell transplantation. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. Methods: We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. Pain at activity and rest, shoulder function and tear size were evaluated. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. The primary outcome measure was the improvement in pain at activity at 3 months after injection. Results: Twenty-three patients were included in the final analysis. Primary outcome did not differ among groups (p = 0·35). A mixed effect model revealed no statistically significant interactions. Only time significantly predicted the outcome measure. All participants reported transient pain at the injection site. There were no differences in post-injection pain duration or severity. Safety measures did not differ between groups, and there were no persistent adverse events. Conclusions: Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections. Trial Registration: ClinicalTrials.gov Identifier: NCT02298023 Funding: This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1512) and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. 2017M3A9D8048711). Declaration of Interest: None to declare. Ethical Approval: Informed consent were approved by the institutional review board (IRB No. 1404-120-575) of our hospital and the Korean Ministry of Food and Drug Safety.

Based on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort.This study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA.The mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%.This multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC.

Research Objectives To evaluate the relationship between several measures of sarcopenia and incidence of falls in elderly. Design A 2-year prospective cohort study. Setting Community. Participants A total of 2252 subjects (1065 males; 1187 females; 70-84 years) were recruited. Interventions Demographic information, comorbidities and history of falls within 1 year were assessed. Cognitive performance was assessed using the Korean version of Mini Mental State Examination (K-MMSE) and muscle mass was measured via dual-energy X-ray absorptiometry. Grip strength and gait speed also measured at baseline and 2-year follow-up. Main Outcome Measures History of falls within 1 year at 2-year follow-up. Results History of previous falls and poor cognitive performance at baseline were significantly associated with incidence of falls during follow-up period. Subjects who had fallen during follow-up period showed poor hand grip strength and poor gait speed compared with those who had not. In females, the muscle mass index of body mass index (BMI) adjustment were significantly associated with incidence of falls. Multiple logistic regression analysis revealed that poor gait speed was a significant risk factor of falling in females. Conclusions The predictive value of individual measures of sarcopenia vary by genders. Poor physical performance was significantly associated with incidence of falls in females, but there was no significant associations between muscle mass indices, strength, and physical performance and falling in males. Author(s) Disclosures No conflict of interest.

Both sarcopenia and obesity are associated with decreased physical function of the elderly. Sarcopenic obesity (SO), which is the coexistence of sarcopenia and obesity, is expected to have a synergistic effect on physical function deterioration, but previous studies have shown varied results. This study aimed to investigate the impact of SO on the physical function of the elderly.Community-dwelling elderly subjects (1091 males; 1212 females; 70-84 years) were recruited in South Korea (eight cities). Body composition was measured via dual-energy X-ray absorptiometry and physical function was measured by grip strength, timed up and go test, and short physical performance battery (SPPB).In males, grip strength and the total SPPB score in the SO group were significantly lower than those in the normal or pure obesity groups (p 0.05). However, physical functions were not significantly different between the SO and the pure sarcopenia groups (p 0.05). The trend for grip strength in females was similar to that in males, but the total SPPB score of the SO group was significantly lower than that of the other three groups (p 0.05). Logistic regression analysis after covariate adjustment revealed that SO group males exhibited the highest risk of being in the lower SBBP score category (OR, 2.12; 95 % CI = 1.04-4.31); this trend was more prominent in females (OR, 3.75; 95 % CI = 2.01-7.00).SO has a synergistic effect on physical function deterioration in the elderly compared with sarcopenia or obesity alone. Additionally, such an effect is more remarkable in females.

Piezoceramic systems [(Bi0.5Na0.5)0.935Ba0.065)]1-yLayTi1-zTazO3 (BNBT-LT) with (y, z) = (0, 0), (0.01, 0.01), (0.02, 0.01), (0.03, 0.01) and (0.04, 0.01) have been synthesized using solid state reaction method. The effect of La3+ and Ta5+ on the structural, ferroelectric, dielectric, bipolar and unipolar strain properties of the parent matrix BNBT was studied. X-ray diffraction (XRD) spectra of samples with (y, z) ≤ (0.01, 0.01) were of ABO3 character and indexed according to the coexistence of rhombohedral and tetragonal symmetry; whereas the systems with (y, z) = (0.02, 0.01), (0.03, 0.01) demonstrated coalescence of reflections (200) & (002) into a single peak (200), indicating a (rhombohedral & tetragonal) ↔ (pseudocubic) structural phase transition. The polarization & strain vs. field loops of the LT rich systems displayed diffused phase transition. The system (x, y) = (0.02, 0.01) attained highest value of strain (0.38%) and dynamic strain ( d 33 ∗ = 542 p.m./V) under the field 70 kV/cm.

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate the actions of the thyroid hormone (T3) in development, growth, and differentiation. The THRA and THRB genes encode several TR isoforms that express in a tissue- and development-dependent manner. In the past decades, a significant advance has been made in the understanding of TR actions in maintaining normal cellular functions. However, the roles of TRs in human cancer are less well understood. The reduced expression of TRs because of hypermethylation, or deletion of TR genes found in human cancers suggests that TRs could function as tumor suppressors. A close association of somatic mutations of TRs with human cancers further supports the notion that the loss of normal functions of TR could lead to uncontrolled growth and loss of cell differentiation.In line with the findings from association studies in human cancers, mice deficient in total functional TRs (Thra1(-/-)Thrb(-/-) mice) or with a targeted homozygous mutation of the Thrb gene (denoted PV; Thrb(PV/PV) mice) spontaneously develop metastatic thyroid carcinoma. This review will examine the evidence learned from these genetically engineered mice that provided strong evidence to support the critical role of TRs in human cancer.Loss of normal functions of TR by deletion or by mutations could contribute to cancer development, progression and metastasis.Novel mechanistic insights are revealed in how aberrant TR activities lead to carcinogenesis. Mouse models of thyroid cancer provide opportunities to identify molecular targets as potential treatment modalities. This article is part of a Special Issue entitled Thyroid hormone signalling.

Introduction Patients with metastatic thyroid cancers that do not uptake iodine need effective therapeutic option. Differentiation-inducing agents have been tried to restore functional expression of sodium iodide symporter (NIS) without success. Our objective was to assess the effect of alpha-lipoic acid (ALA), known as potential antioxidant, on expression of sodium iodide symporter in thyroid cancer cells. Methods Human thyroid cancer-derived cell lines, TPC-1, were treated with ALA, and changes in NIS mRNA and protein expression were measured. ALA's effect on NIS gene promoter was evaluated, and functional NIS expression was assessed by iodide uptake assay. Results Treatment with ALA increased NIS mRNA expression up to ten folds of control dose-dependently after 24 h of exposure. ALA increased NIS promoter activity, and increased iodide uptake by 1.6 fold. ALA induced expression of NIS protein, but had no significant effect on the plasma membrane trafficking. ALA increased phosphorylation of CREB and nuclear translocation of pCREB, and co-treatment of ALA and trichostatin A increased iodide uptake by three folds in TPC-1 cells. Conclusions ALA is a potential agent to increase NIS transcription in TPC-1. It could be used as an adjunctive agent to increase efficacy of radioiodine therapy if combined with a strategy to increase NIS protein trafficking to cell membrane.

Purpose Few studies specify the methods used to measure ST-segment elevation (STE). We therefore assessed differences in electrocardiography results depending on STE measurement methods for patients with inferior acute myocardial infarction (MI) and right ventricular infarction. Methods This study was a retrospective analysis. The STE group consisted of 88 patients consecutively admitted to the emergency department with inferior ST elevation MI associated with occlusion of right coronary artery or left circumflex coronary artery who underwent primary percutaneous coronary intervention. The control group consisted of 109 patients with non–ST elevation MI who had occlusion of right coronary artery or left circumflex coronary artery and underwent percutaneous coronary intervention. Measurements were performed at the J point and 60 milliseconds later for limb lead and right precordial V 4 lead (V4R). The criterion of at least 1-mm STE in 2 consecutive leads was applied, and the diagnostic accuracy of V4R was calculated. Results In the STE group, the measurements 60 milliseconds after the J point were significantly higher than measurements at the J point at the II, III, aVF, and V4R leads. In the control group, only the measurements at lead I differed significantly. There was a 5% difference in diagnostic sensitivity depending on the measuring points in the STE group, a 1% to 3% difference in the control group, and a 10% to 11% difference at the V4R lead. Conclusion In patients with inferior MI, STE depends on the method of measurement, indicating a need for the standardization of measurements.

The purpose of this article was to identify the risk factors related to development of hemodynamically significant cardiac arrhythmias in patients with mechanical ventilation.Holter recording and echocardiogram were performed within 24 hours of ventilator initiation in patients on mechanical ventilation (MV) owing to respiratory failure (RF) from various reasons.From 68 patients, hemodynamically significant cardiac arrhythmias were detected in 18 patients (26.5%). Initial mean arterial pressure, maximal heart rate, and initial pH were identified as risk factors for hemodynamically significant cardiac arrhythmias. Additionally, the patients with pressure-controlled ventilation as an initial ventilatory mode developed hemodynamically significant cardiac arrhythmias less frequently than the patients with other modes (15.8% vs. 40%, P = .03). In multivariate analysis, initial mean arterial pressure (70 mm Hg, odds ratio [OR]: 5.5; 95% confidence interval [CI]: 1.2 to 24.2, P = .026), maximal heart rate (120/min, OR: 19.7; 95% CI: 2.0 to 190.9, P = .01), and pressure-controlled ventilation (OR: 0.13; 95% CI: 0.03 to 0.55, P = .006) were associated with the development of hemodynamically significant cardiac arrhythmias.These findings suggest that during the early stages of mechanical ventilation with acute respiratory failure, hemodynamically significant cardiac arrhythmias are directly associated with tachycardia (or = 120/min), initial MAP (70 mm Hg), and, inversely, the initial use of pressure-controlled ventilation.