Association between primary hyperparathyroidism and cardiovascular outcomes: A systematic review and meta-analysis.

BACKGROUND: Excess parathyroid hormone (PTH) is associated with an increased risk of cardiovascular disease (CVD). PURPOSE: We aimed to evaluate the correlation between primary hyperparathyroidism (PHPT) and CVD or cardiovascular (CV) death. DATA SOURCES: Comprehensive searches of PubMed, Embase and ClinicalTrials.gov until May 20, 2023 with the following keywords: "primary hyperparathyroidism," "cardiovascular disease," and "mortality." STUDY SELECTIONS: Cohort studies and randomized controlled trials comparing PHPT patients to the general population and those who had received parathyroidectomy (PTX) to those who did not. DATA EXTRACTION: Three investigators independently extracted data and assessed study quality. DATA SYNTHESIS: Eleven cohort studies and one randomized controlled trial were identified, including 264,227 PHPT patients with or without PTX, and the average age reported in the studies was 62 years. PHPT was associated with a higher risk of total death (RR 1.39 [95 % confidence interval (CI) 1.23-1.57) and CV death (RR 1.61 [95 % CI 1.47-1.78]) than the general population. However, there was no significant difference in CVD risk between patients with PHPT and the general population (RR 1.73 [95 % CI 0.87-3.47]). When compared to patients without PTX, PTX had a lower risk of CV death (RR 0.75 [95 % CI 0.71-0.80]), total death (RR 0.64 [95 % CI 0.60-0.70]) and CVD (RR 0.92 [95 % CI 0.90-0.94]). LIMITATION: High heterogeneity among the included articles, and most of them were retrospective and older studies. CONCLUSIONS: PHPT was associated with higher risk of total death and CV death while PTX was associated with lower risk of total death, CV death, and CVD.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

ELUCIDATE Trial: A Single-Center Randomized Controlled Study.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, is an epochal oral antidiabetic drug that improves cardiorenal outcomes. However, the effect of early dapagliflozin intervention on left ventricular (LV) remodeling in patients with type 2 diabetes free from cardiovascular disease remains unclear. METHODS AND RESULTS: The ELUCIDATE trial was a prospective, open-label, randomized, active-controlled study that enrolled 76 patients with asymptomatic type 2 diabetes with LV ejection fraction ≥50%, randomized to the dapagliflozin 10 mg/day add-on or standard-of-care group. Speckle-tracking echocardiography-based measurements of the cardiac global longitudinal strain were performed at baseline and 24 weeks after treatment initiation. Patients who received dapagliflozin had a greater reduction in LV dimension (1.68 mm [95% CI, 0.53-2.84]; P=0.005), LV end-systolic volume (5.51 mL [95% CI, 0.86-10.17]; P=0.021), and LV mass index (4.25 g/m2.7 [95% CI, 2.42-6.09]; P<0.0001) compared with standard of care in absolute mean differences. Dapagliflozin add-on therapy led to a significant LV global longitudinal strain increment (0.74% [95% CI, 1.00-0.49]; P<0.0001) and improved LV systolic and early diastolic strain rates (0.27/s [95% CI, 0.17-0.60]; and 0.11/s [95% CI, 0.06-0.16], respectively; both P<0.0001) but not in global circumferential strain. No significant changes were found in insulin resistance, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, or other biomarkers at 6 months after the dapagliflozin administration. CONCLUSIONS: Dapagliflozin add-on therapy could lead to more favorable cardiac remodeling accompanied by enhanced cardiac mechanical function among patients with asymptomatic type 2 diabetes. Our findings provide evidence of the efficacy of dapagliflozin use for the primary prevention of diabetic cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03871621.

Acromegaly with initial negative oral glucose tolerance test: a case report.

BACKGROUND: Acromegaly can be diagnosed by a growth hormone value ≥ 1 µg/L following an oral glucose tolerance test. However, normal growth hormone suppression following oral glucose tolerance test may not exclude acromegaly. CASE PRESENTATION: We present a case of a 55-year-old Chinese man with pituitary macroadenoma incidentally noted after a traffic accident. He reported feet enlargement in the past few years. At the beginning, elevated insulin-like growth factor-1 was noted with growth hormone value < 1 µg/L after oral glucose tolerance test. Fracture-related high insulin-like growth factor-1 was suspected. Insulin-like growth factor-1 decreased gradually but was still above the upper limit of normal . However, he suffered from dizziness 1 year later and insulin-like growth factor-1 increased again. Besides, secondary hypocortisolism developed. The size of the pituitary macroadenoma was stationary. Follow-up oral glucose tolerance test showed a growth hormone value > 1 µg/L. Endoscopic endonasal approach to the remove pituitary macroadenoma was performed subsequently. After the resection of the pituitary macroadenoma, pathology showed positive staining of growth hormone and prolactin. Insulin-like growth factor-1 normalized as well. CONCLUSIONS: Suppressed growth hormone after oral glucose tolerance test cannot exclude acromegaly, and some patients may have only mild or no clinical presentation of acromegaly. Patients with pituitary microadenoma or macroadenoma and elevated insulin-like growth factor-1 should be closely monitored for signs/symptoms of acromegaly and hypopituitarism.

A Clinicopathological Analysis of Asian Patients with Adrenocortical Carcinoma: A Single-Center Experience.

BACKGROUND: There is limited information regarding the immunohistochemistry stain and its prognostic role in adrenocortical carcinoma (ACC), and few studies focus on Asian patients. Our study aims to identify the correlation between immunohistochemistry staining and the prognosis of ACC in Asian patients. METHODS: We searched the database of a single center in Taiwan for cases with a pathological diagnosis of ACC in the past 25 years. We collected patient data on age, sex, initial presentation, staging, metastatic site, and survival duration. Immunohistochemical studies using antibodies to CDK4, ATRX, beta-catenin, Ki-67, SSTR2, and p53 were performed. Survival analysis was performed using the log-rank test, the Cox proportional hazards model and bootstrapping with 5000 samplings. RESULTS: Fourteen patients were identified, and the median age was 49.5 (range 1-70) years. There were eight male and six female patients. Four patients presented with Cushing's syndrome, and half were diagnosed with stage IV ACC at presentation. Only three patients survived (21%). The median survival time was 15.5 (range 0.67-244) months. SSTR2 expression score > 50 (log-rank test: p = 0.009) and Ki-67 > 50% (log-rank test: p = 0.017) were associated with mortality. However, after adjusting for stage, the bootstrapping analysis demonstrated that Ki-67 [B 2.04, p = 0.004], Beta-catenin [B 2.19, p = 0.009], ATRX [B 1.48, p = 0.026], P53 [B 1.58, p = 0.027], SSTR2 [B 1.58, p = 0.015] and SSTR2 expression score [B 0.03, p < 0.001] were all significantly associated with mortality. CONCLUSIONS: After adjusting for stage, Ki-67 > 50%, Beta-catenin, ATRX, P53, SSTR2 and SSTR2 expression score > 50 were associated with mortality in Asian patients with ACC.

Impact of social and economic factors on global thyroid cancer incidence and mortality.

PURPOSE: The incidence of thyroid cancer has increased substantially over the past few decades and is partially explained by overdiagnosis. Geographical variations in incidence rates were reported to be related to national development status. This study aimed to gain deeper insights into global thyroid cancer burden by incorporating additional social and economic factors to account for cross-national disparities. METHODS: We performed a multivariate analysis of age-standardized incidence and mortality data from the GLOBOCAN 2020 database for 126 countries that had more than 100 incident cases of thyroid cancer. The human development index (HDI), current health expenditure, and additional Global Health Observatory indicators were extracted from multiple sources. RESULTS: Age-standardized incidence was highly correlated with HDI (standardized coefficient beta = 0.523, 95% confidence interval [CI] = 0.275-0.771) among the countries studied. The prevalence of raised fasting blood glucose was associated with age-standardized mortality (beta = 0.277, 95% CI = 0.038-0.517). Generally, the mortality-to-incidence ratio was higher in males than in females. In multivariate analysis, HDI (beta = - 0.767, 95% CI = - 0.902 to - 0.633), current health expenditure (beta = 0.265, 95% CI = 0.137-0.394), and fine particulate matter (PM2.5) concentrations (beta = 0.192, 95% CI = 0.086-0.298) were associated with mortality-to-incidence ratios. CONCLUSIONS: National developments gauged by HDI explain the majority of the variation in incidence rates of thyroid cancer but play a smaller role in disparities in mortality rates. The association between air pollution and thyroid cancer outcomes warrants further investigation.

Association between thyroid cancer and cardiovascular disease: A meta-analysis.

Objective: To determine the association between thyroid cancer and coronary artery disease, atrial fibrillation, cerebrovascular disease, and cardiovascular disease mortality. Methods: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to September 22, 2022. Keywords included "thyroid cancer", "atrial fibrillation", "coronary artery disease", "cerebrovascular disease", and "mortality". Primary outcomes included the incidence of coronary artery disease, cerebrovascular disease, atrial fibrillation, and cardiovascular disease mortality among patients with thyroid cancer. Secondary outcomes included cardiovascular disease events among those with thyroid cancer that received or did not receive radioactive iodine or lenvatinib. Estimates were pooled using fixed- and random-effects meta-analysis. Results: A total of 771,220 patients who underwent thyroidectomy in 15 studies were included. Risk for cerebrovascular disease (risk ratio [RR] 1.15 [95% confidence interval (CI) 1.10-1.21]) and atrial fibrillation [RR 1.59 (95% CI: 1.45-1.73)] were significantly increased. Risk for coronary artery disease was significantly increased [RR 1.12 (95% CI: 1.08-1.17)] in the common effect model. Cardiovascular disease mortality associated with thyroid cancer was not significant [RR 0.93 (95% CI: 0.59-1.45)]. Radioactive iodine had a neutral effect on cardiovascular disease [RR 1.00 (95% CI: 0.87-1.16)], and there was no beneficial nor harmful effect among different RAI doses. Conclusions: Thyroid cancer was significantly associated with a higher risk for cerebrovascular disease and atrial fibrillation; however, the hazard risk was not different between patients with and without radioactive iodine treatment. Thyroid cancer treatment should be individualized considering the potential harms and benefits to cardiovascular health.

Comparison of two titration programmes for adding insulin detemir to oral antidiabetic drugs in patients with poorly controlled type 2 diabetes mellitus.

AIM: To explore the effect of active insulin titration versus usual titration on glycaemic control in patients with type 2 diabetes mellitus uncontrolled with oral antidiabetic drugs (OADs). METHODS: In a 24-week, prospective and randomized study, 172 patients with uncontrolled type 2 diabetes were randomly assigned to either active titration or usual titration. Efficacy and safety outcomes included changes in glycated haemoglobin (HbA1c) and fasting plasma glucose, percentage of individuals achieving HbA1c<53 mmol/mol, and hypoglycaemic events. RESULTS: At Week 24, change in HbA1c was -1.08% ± 1.60% in the active titration group and -0.95% ± 1.34% in the usual titration group (P = 0.569). The percentages of individuals achieving HbA1c<53 mmol/mol were 29.4% and 16.1% in the active and usual titration groups, respectively (P = 0.037). There was no significant difference in the incidence of hypoglycaemia between the two groups. Multivariate logistic regression indicated that, with active titration, baseline HbA1c levels and postprandial glucose excursion were significantly associated with achieving HbA1c<53 mmol/mol. CONCLUSION: Addition of basal insulin using active titration for 24 weeks provided a higher rate of HbA1c target achievement without significant hypoglycaemia compared to usual titration in individuals with uncontrolled type 2 diabetes.

Risk of fracture caused by anti-diabetic drugs in individuals with type 2 diabetes: A network meta-analysis.

AIMS: Diabetes is associated with increased risk of fracture. This study aims to evaluate the correlation between anti-diabetic agents and fracture risk in patients with type 2 diabetes. METHODS: Literature research was conducted using PubMed, Embase, and ClinicalTrials.gov. Search-term included "type 2 diabetes," "fracture," "randomized controlled trial," and seven kinds of anti-diabetic agents. Random-effect models established fractures in the follow-up period as the primary outcome. A network meta-analysis was performed to compare available treatments within a single Bayesian analytical framework. RESULTS: A total of 191,361 patients were included in 161 studies, with 2916 fractures. DPP-4i (risk ratio [RR] 1.76 [95 % confidence interval (CI) 1.21-2.55]), SGLT-2i (RR 1.5 [95 % CI 1.05-2.16]) and placebo (RR 1.44 [95 % CI 1.04-1.98]) increased fracture risk when compared to GLP1-RA. GLP1-RA (RR 0.5 [95 % CI 0.31-0.79]) and SU (RR 0.56 [95 % CI 0.41-0.77]) provided greater protection against fracture than TZD. DPP-4i increased fracture risk when compared to SU (RR 1.55 [95 % CI 1.08-2.22]), and was comparable in effect to TZD. CONCLUSIONS: GLP1-RA offered better protection against fracture than placebo. Insulin and SU had effects comparable with GLP1-RA. SU offered greater protection against fractures than TZD and DPP-4i. SGLT-2i increased risk of fracture when compared to GLP1-RA.

Transcriptomic Characteristics Associated With Aging in the Thyroid Gland.

The aging thyroid is associated with a plethora of morphological and functional changes. Limited studies have addressed the gene expression signature in the aging thyroid, except for sporadic reports using data from postmortem samples in the Genotype-Tissue Expression (GTEx) project. In this investigation, we analyzed the RNA sequencing data of 58 samples of normal-appearing counterpart thyroid tissues from The Cancer Genome Atlas. Aging-correlated genes were identified by determining the Spearman rank-order correlation between patient age and gene expression level. Additionally, we performed gene set enrichment analysis and conducted a weighted correlation network analysis. The results were compared with those analyzed using the GTEx data. The over-represented protein class of aging-correlated genes is mainly metabolite interconversion enzymes. Our analyses identified alterations in immune and inflammatory responses, mitochondrial functions, cytoskeletal proteins, as well as amino acid and cytochrome P450 metabolism. There was no significant association between thyroid differentiation and age. Our findings may shed molecular light on thyroid disorders in the geriatric population.

Adrenal Gland Irradiation Causes Fatigue Accompanied by Reactive Changes in Cortisol Levels.

BACKGROUND: Incidental radiotherapy (RT) to the adrenal gland may have systemic effects. This study aimed to investigate the effects of adrenal RT on fatigue. METHODS: BALB/c mice were surgically explored to identify the left adrenal gland and delivered intra-operative RT. The swimming endurance test was used for endurance assessment to represent fatigue. Plasma levels of stress hormones and histopathological features were examined. Three patients with inevitable RT to the adrenal gland were enrolled for the preliminary study. Serum levels of cortisol, aldosterone, and adrenocorticotropic hormone (ACTH) were measured before and after RT. Fatigue score by using the fatigue severity scale and RT dosimetric parameters were collected. RESULTS: In the experimental mouse model, adrenal RT decreased baseline cortisol from 274.6 ± 37.8 to 193.6 ± 29.4 ng/mL (p = 0.007) and swimming endurance time from 3.7 ± 0.3 to 1.7 ± 0.6 min (p = 0.02). In histopathological assessment, the irradiated adrenal glands showed RT injury features in the adrenal cortex. In the enrolled patients, baseline cortisol significantly declined after RT. There were no significant differences in the levels of morning cortisol, aldosterone, and ACTH before and after RT. CONCLUSIONS: The RT dose distributed to the adrenal gland may correlate with unwanted adverse effects, including fatigue and adrenal hormone alterations.

Continuous Glucose Monitoring System Based on Percutaneous Microneedle Array.

A continuous blood glucose monitoring system (CGMS) which include a microneedle-array blood glucose sensor, a circuit module, and a transmission module placed in a wearable device is developed in this research. When in use, the wearable device is attached to the human body with the microneedle array inserted under the skin for continuous blood glucose sensing, and the measured signals are transmitted wirelessly to a mobile phone or computer for analysis. The purpose of this study is to replace the conventionally used method of puncture for blood collection and test strips are used to measure the blood glucose signals. The microneedle sensor of this CGMS uses a 1 mm length needle in a 3 mm × 3 mm microneedle array for percutaneous minimally invasive blood glucose measurement. This size of microneedle does not cause bleeding damage to the body when used. The microneedle sensor is placed under the skin and their solutions are discussed. The blood glucose sensor measured the in vitro simulant fluid with a glucose concentration range of 50~400 mg/dL. In addition, a micro-transfer method is developed to accurately deposit the enzyme onto the tip of the microneedle, after which cyclic voltammetry (CV) is used to measure the glucose simulation solution to verify whether the difference in the amount of enzyme on each microneedle is less than 10%. Finally, various experiments and analyses are carried out to reduce the size of the device, test effective durability (approximately 7 days), and the feasibility of minimally invasive CGMS is evaluated by tests on two persons.

Continuous Lactate Monitoring System Based on Percutaneous Microneedle Array.

Lactate measurement is important in the fields of sports and medicine. Lactate accumulation can seriously affect an athlete's performance. The most common problem caused by lactate accumulation in athletes is muscle soreness due to excessive exercise. Moreover, from a medical viewpoint, lactate is one of the main prognostic factors of sepsis. Currently, blood sampling is the most common approach to lactate measurement for lactate sensing, and continuous measurement is not available. In this study, a low-cost continuous lactate monitoring system (CLMS) is developed based on a percutaneous microneedle array that uses a three-electrode lactate sensor. The working electrode has an area of 10 mm × 6 mm, including a 3 × 3 array of stainless-steel microneedles. The length, width, and thickness of each needle are 1 mm, 0.44 mm, and 0.03 mm, respectively. The working electrode is then plated with gold, polyaniline, lactate enzyme, Nafion, and Poly(2-hydroxyethyl methacrylate) (poly HEMA). The reference electrode is a 2 × 1 array covered with AgCl, and the counter electrode is a 2 × 1 array plated with gold. The sensor is incorporated into the CLMS and connected to a smartphone application and the cloud. The CLMS was tested on 40 human subjects who rode indoor bicycles, starting at 100 W and increasing in steps of 25 W at intervals of 5 min until exhaustion. The data acquired from the app connected to the CLMS were analyzed to determine the subjects' lactate response to exercise and the feasibility of assessing exercise performance and training exercise intensity by using the proposed system.

SREBP1 promotes invasive phenotypes by upregulating CYR61/CTGF via the Hippo-YAP pathway.

Aberrant lipid metabolism provides bioenergetic, biosynthetic, and redox supplies to cancer cells. Previous studies have reported differential lipid profiling in thyroid malignancies. Sterol regulatory element-binding protein 1 (SREBP1), encoded by the SREBF1 gene, is a master regulator of cellular lipid homeostasis. The clinical and functional significance of SREBP1 in thyroid cancer is not well understood. Here, we showed that SREBP1 expression is significantly upregulated in invasive thyroid cancer than in normal thyroid tissue or benign thyroid nodules. High tumoral SREBP1 expression was associated with extrathyroidal extension, advanced disease stage, and shorter disease-specific survival in patients with differentiated thyroid cancer. SREBP1 overexpression significantly increased the oxygen consumption rate, filopodia formation, and migratory and invasive capacities of thyroid cancer cells. Knockdown of SREBF1 or treatment with an SREBP1 activation inhibitor fatostatin had the opposite effect. RNA-Seq analysis showed that modulation of SREBP1 expression was accompanied by corresponding changes in the expression of epithelial-mesenchymal transition markers and CYR61/CTGF. SREBP1-facilitated cell invasion could be abrogated by treatment with a YAP inhibitor such as verteporfin or genetic silencing of CYR61 or CTGF. In summary, SREBP1 upregulation can be used as a prognostic indicator for thyroid cancer and SREBP1 overexpression is involved in cancer invasiveness, at least partly, through upregulation of CYR61/CTGF via the Hippo-YAP pathway.

Effects of SGLT2 inhibitors on stroke and its subtypes in patients with type 2 diabetes: a systematic review and meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effects in reducing major vascular events in several randomized controlled trials (RCTs). The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitors on the risk of stroke and its subtypes. All data from prospective RCTs up to 20 October 2020 involving SGLT2 inhibitors that reported stroke events as the primary endpoint or safety in subjects with type 2 diabetes were subjected to meta-analysis. Five eligible RCTs (EMPA-REG, CANVAS, DECLARE-TIMI 58, CREDENCE and VERTIS CV) involving 46,969 participants were included. Pooled analysis of the RCTs showed no significant effect of SGLT2 inhibitors on total stroke [risk ratio (RR) = 0.95; 95% confidence interval (CI) 0.79-1.13, P = 0.585]. Subgroup analysis indicated that SGLT2 inhibitors had no significant effect against fatal stroke, non-fatal stroke, ischemic stroke or transient ischemic attack. When only hemorrhagic stroke was included, SGLT2 inhibitors were associated with a significant 50% reduction compared with placebo (RR = 0.49, 95% CI 0.30-0.82, P = 0.007). This meta-analysis shows that SGLT2 inhibitors have a neutral effect on the risk of stroke and its subtypes but a potential protective effect against hemorrhagic stroke.

Preoperative Factors Associated with Extrathyroidal Extension in Papillary Thyroid Cancer.

OBJECTIVE: Extrathyroidal extension may not be accurately recognized during thyroidectomy and can increase the risk of positive margins and even recurrence. This study aimed to investigate the preoperative factors associated with extrathyroidal extension. METHODS: We analyzed 887 patients with papillary thyroid cancer (PTC) who underwent surgery in the period of 2005-2017. Binary logistic regression analyses and generalized additive models were used to identify associations. RESULTS: Minimal extrathyroidal extension was present in 233 (26%) patients and advanced extrathyroidal extension was found in 60 (7%) patients. Age, BMI, and tumor size were independent predictors of all or advanced extrathyroidal extension. Among the 493 patients whose BRAF mutation status was available, age (OR = 1.025), BMI (OR = 1.091), tumor size (OR = 1.544), and BRAF V600E mutation (OR = 2.311) were independently associated with extrathyroidal extension. CONCLUSIONS: Older age, a greater BMI, a larger tumor size, and presence of the BRAF mutation were predictive of extrathyroidal extension. These factors should be taken into consideration in decision-making before surgery is performed.

Lymphovascular invasion of papillary thyroid carcinoma revisited in the era of active surveillance.

INTRODUCTION: Lymphovascular invasion (LVI) is associated with disease recurrence and compromised survival in patients with thyroid cancer. Nonetheless, LVI is not identifiable on preoperative ultrasound or cytologic assessment. We aimed to explore the clinicopathological features associated with LVI. PATIENTS AND METHODS: We conducted a retrospective review of our prospectively maintained database from 2009 to 2018. Multivariate analyses were performed to determine the associations between clinicopathological parameters and LVI. Generalized additive models were used to examine the nonlinear relationship between continuous variables and LVI. RESULTS: A total of 795 patients were included in the analysis, and 174 (22%) had LVI. Patients' age (odds ratio [OR] = 0.982), tumor size (OR = 1.466), clinical lymphadenopathy (OR = 6.975), and advanced extrathyroidal extension (OR = 2.938) were independently associated with LVI. In the subset analysis of 198 patients with available genetic information, tumor size (OR = 1.599), clinical lymph node metastasis (OR = 3.657), and TERT promoter mutation (OR = 4.726) were predictive of LVI. Among 573 patients who had no clinical lymphadenopathy or advanced extrathyroidal extension, tumor size was the only predictor of LVI. Tumor size >1.5 cm had an increased risk of LVI based on the generalized additive model plot and receiver operating characteristic curve analysis. CONCLUSION: Tumor size is positively associated with the risk of LVI in papillary thyroid cancer. To avoid delayed treatment in patients with LVI, a tumor size of 1.5 cm may be considered as the safe upper limit for active surveillance.

Overexpression of Histone H3 Lysine 27 Trimethylation Is Associated with Aggressiveness and Dedifferentiation of Thyroid Cancer.

A variety of epigenetic dysregulations are observed in thyroid malignancies. EZH2, the catalytic subunit of polycomb repressive complex 2, is upregulated in advanced thyroid cancers. EZH2 can catalyze trimethylation of histone H3 at lysine 27 (H3K27me3) and contribute to transcriptional silencing of target genes. Here, we investigated the immunohistochemical expression of H3K27me3 in neoplastic and normal thyroid tissues. Normal thyroid epithelial cells typically exhibited nuclear staining of moderate intensity. A similar expression pattern was observed in nodular goiters and follicular adenomas. By contrast, strong H3K27me3 expression was evident in 80% (8/10) lymphocytic thyroiditis, 63% (80/127) papillary thyroid cancer, 41% (7/17) follicular thyroid cancer, and 73% (8/11) poorly differentiated and anaplastic thyroid cancer. In differentiated thyroid cancer, strong H3K27me3 expression was associated with extrathyroidal extension (p < 0.001), lymphovascular invasion (p = 0.029), lymph node metastasis (p = 0.006), and higher risk of recurrence (p = 0.003). Our results indicate that H3K27me3 overexpression may be implicated in aggressiveness and dedifferentiation of thyroid cancer. In addition to prognostication, the predictive value of H3K27me3 expression deserves further investigation given the recent development of epigenetic targeting agents.

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score-matched analysis.

BACKGROUND: Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. METHODS: We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity-score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. RESULTS: After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF-like vs RAS-like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix-associated pathways were enriched in the MSigDB database. CONCLUSION: Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.

Association between neutrophil-to-lymphocyte ratio and parathyroid hormone in patients with primary hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is associated with adverse cardiovascular outcomes which may result from an increase in systemic inflammation. Previously we have shown that serum parathyroid hormone (PTH) levels are independently associated with inflammatory indicators. The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive, widely available marker of inflammation. In the present study, we aimed to assess the longitudinal changes in NLR before and after parathyroidectomy. MATERIAL AND METHODS: This retrospective study included 95 patients diagnosed with PHPT who underwent parathyroidectomy between 2006 and 2016. Follow-up complete blood counts were available in 31 patients. RESULTS: At diagnosis, 43 (45%) patients presented with overt clinical symptoms and had higher serum calcium and PTH levels. Preoperative NLR was positively correlated with total white blood cell count (p = 0.001), serum calcium (p = 0.001), and PTH level (p = 0.013). The NLR was not associated with sex, age, comorbidities, or parathyroid weight. Among patients who were cured of PHPT, the median NLR decreased from 2.26 to 1.77 after parathyroidectomy (p = 0.037). There was no difference in hemoglobin, total white blood cells, or platelet count before and after surgery. CONCLUSIONS: We found a positive correlation of preoperative NLR with calcium and PTH levels in PHPT patients. After curative parathyroidectomy, NLR modestly decreased without changes in other hematological parameters.