1-Hour Post-Load Glucose: Early Screening for High Risk of Type 2 Diabetes in Koreans with Normal Fasting Glucose.

CONTEXT: With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. OBJECTIVE: This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. METHODS: 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. RESULTS: At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. CONCLUSION: Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Effectiveness and Usefulness of Bone Turnover Marker in Osteoporosis Patients: A Multicenter Study in Korea.

BACKGROUND: This study aimed to investigate real-world data of C-terminal telopeptide (CTX), propeptide of type I collagen (P1NP), and osteocalcin through present multicenter clinical study, and retrospectively analyze the usefulness of bone turnover markers (BTMs) in Koreans. METHODS: The study focused on pre- and post-menopausal patients diagnosed with osteoporosis and excluded patients without certain test results or with test intervals of over 1 year. The demographic data and 3 BTMs (CTX, P1NP, and osteocalcin) were collected. The patients were classified by demographic characteristics and the BTM concentrations were analyzed by the group. RESULTS: Among women with no history of fractures, the levels of P1NP (N=2,100) were 43.544±36.902, CTX (N=1,855) were 0.373 ±0.927, and osteocalcin (N=219) were 10.81 ±20.631. Among men with no history of fractures, the levels of P1NP (N=221) were 48.498±52.892, CTX (N=201) were 0.370±0.351, and osteocalcin (N=15) were 7.868 ±10.674. Treatment with teriparatide increased the P1NP levels after 3 months in both men and women, with a 50% increase observed in women. Similarly, treatment with denosumab decreased the CTX levels after 3 months in both men and women, with a reduction of 50% observed in women. CONCLUSIONS: The results of this study can contribute to the accurate assessment of bone replacement status in Koreans. We also provide the P1NP level in the Korean population for future comparative studies with other populations.

Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis.

Context: Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed. Objective: This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Data sources: Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. Study selection: We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. Data extraction: We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. Data synthesis: A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Conclusions: Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.

Trabecular Bone Score and Central Quantitative Computed Tomography for the Prediction of Vertebral Fragility Fractures in Postmenopausal Women.

BACKGROUND: We aimed to investigate whether densitometry results and volumetric bone mineral density (vBMD) can predict vertebral fragility fractures (VFF) in postmenopausal women. METHODS: We enrolled 271 postmenopausal women aged >45 years who visited our hospital for health check-ups between September 2016 and September 2017. The lumbar spine (LS) and femoral neck (FN) densitometry results and trabecular bone score (TBS) were calculated using dual energy X-ray absorptiometry. vBMD was assessed using central quantitative computed tomography (cQCT). Baseline and follow-up X-ray images were reviewed to evaluate thoracolumbar vertebral compression fractures (CFs), according to the Genant criteria. RESULTS: At baseline, 76 patients (28.0%) had CF. Additional or progressive fractures were noted in 26 participants (9.6%) with a median follow-up of 19.5 months. The median TBS and cQCT were significantly higher in participants without baseline CF than those with baseline CF (p<0.001). During the follow-up, Kaplan-Meier analysis showed that T-scores of the LS and FN <-2.5, degraded microarchitecture based on the TBS (≤1.200), and vBMD <80 mg/cm3 was significantly associated with future osteoporotic CF. The final multivariate Cox regression analysis showed that baseline CF and low TBS and vBMD were significant risk factors for future VFF. CONCLUSIONS: Participants with baseline CF and degraded microarchitecture had higher CF predisposition. Moreover, cQCT can predict future vertebral fractures.

Heart Failure and Stroke Risks in Users of Liothyronine With or Without Levothyroxine Compared with Levothyroxine Alone: A Propensity Score-Matched Analysis.

Background: Combination therapy with liothyronine (LT3) and levothyroxine (LT4) is used in patients with persistent symptoms, despite being administered an adequate dose of LT4. LT3 may also be used in some thyroid cancer patients preparing for radioactive iodine therapy. However, there is a controversy regarding the safety of LT3 use, and there has been no definite evidence of long-term safety of LT3 therapy in Asian populations. The aim of this study was to examine the long-term safety of LT3 therapy using the Common Data Model (CDM). Methods: We conducted a retrospective multicenter study across four hospital databases encoded in the Observational Medical Outcomes Partnership (OMOP) CDM. LT3 users were defined as those who received an LT3 prescription for at least 90 days (with or without LT4), and their safety outcomes were compared with those in LT4-only users after 1:4 propensity score matching. Safety outcomes included the incidences of osteoporosis, cardiovascular disease, cancer, anxiety disorder, and mood disorder. Results: We identified 1434 LT3 users and 3908 LT4-only users. There was a statistically significant difference in the incidence rate of safety outcomes between LT3 users and LT4-only users. The risks of heart failure (incidence rate ratio [IRR] = 1.664, 95% confidence interval [95% CI] 1.002-2.764, p = 0.049) and stroke (IRR = 1.757, CI 1.073-2.877, p = 0.025) were higher in LT3 users than in LT4-only users. When subgroup analysis was performed according to the presence/absence of thyroid cancer history and duration of thyroid hormone replacement, the risk of heart failure was higher in LT3 users with a history of thyroid cancer and those who underwent ≥52 weeks of LT3 therapy. In addition, the risk of stroke was higher in LT3 users without thyroid cancer history and those who underwent ≥52 weeks of LT3 therapy. Conclusions: The use of LT3 was associated with increased incidence of heart failure and stroke in patients with a longer duration of LT3 use and history of thyroid cancer. Therefore, clinicians should consider the risk of heart failure and stroke in thyroid cancer patients with long-term use of LT3. These findings require confirmation in other populations.

Effect of oligonol, a lychee-derived polyphenol, on skeletal muscle in ovariectomized rats by regulating body composition, protein turnover, and mitochondrial quality signaling.

Oligonol is a low-molecular-weight polyphenol product derived from lychee (Litchi chinensis Sonn.) fruits. This study was focused on the effects of oligonol on the skeletal muscle of ovariectomized rats. We randomly divided female Sprague-Dawley rats into three groups: a sham surgery control group (Sham), an ovariectomy (OVX) group, and an OVX group treated with oligonol (OVX + Oligonol). Oligonol was intraperitoneally administrated at 30 mg/kg daily for 6 weeks. Oligonol treatment after OVX decreased body weight and fat mass, regulated lipid metabolism in skeletal muscle, without loss of lean mass and bone. Bone turnover was not affected by oligonol. In protein synthesis and degradation, oligonol increased the levels of the mammalian target of rapamycin and its downstream targets, eukaryotic initiation factor 4E-binding protein 1 and 70-kDa ribosomal protein S6 kinase, and it stimulated the expression of ubiquitin-proteasome pathway proteins, the forkhead box transcription factors of the class O and the muscle ring-finger protein-1. Moreover, oligonol treatment enhanced mitochondrial biogenesis and dynamics. Thus, our results indicated that oligonol treatment had beneficial effects on the skeletal muscle in an estrogen-deficiency rat model.

Association between visceral adipose tissue volume, measured using computed tomography, and cardio-metabolic risk factors.

We evaluated the associations between metabolic parameters with visceral adipose tissue (VAT) volume in women with prediabetes or type 2 diabetes (T2DM), and we compared the VAT volume with the VAT area. We enrolled women aged > 20 years with prediabetes or T2DM, who underwent oral glucose tolerance test and whose VAT was evaluated using computed tomography (CT) at our institution between 2017 and 2019. All participants underwent unenhanced spiral CT with a 3-mm slice thickness from the level of the diaphragm to the level of the mid-thigh. The two VAT areas were defined as the free drawn area on the levels of the umbilicus and L2 vertebra. The VAT areas were also manually drawn from the level of the diaphragm to the level of the pelvic floor and were used to calculate the VAT volumes by summing all areas with a slice thickness of 3 mm after setting the attenuation values from -45 to -195 Hounsfield Unit. All metabolic characteristics, except blood pressure, were significantly correlated with the VAT volume. The VAT areas measured at the level of the L2 vertebra and umbilicus were correlated with serum triglyceride, high-density lipoprotein cholesterol, and Framingham steatosis index alone. Multivariable regression analyses revealed that the VAT volume was significantly associated with several metabolic parameters. In conclusion, in women with prediabetes and T2DM, the VAT volume acquired from CT-based calculation has more significant correlations with metabolic risk factors compared with the VAT area.

Whole-Exome Sequencing in Papillary Microcarcinoma: Potential Early Biomarkers of Lateral Lymph Node Metastasis.

BACKGROUND: Early identification of patients with high-risk papillary thyroid microcarcinoma (PTMC) that is likely to progress has become a critical challenge. We aimed to identify somatic mutations associated with lateral neck lymph node (LN) metastasis (N1b) in patients with PTMC. METHODS: Whole-exome sequencing (WES) of 14 PTMCs with no LN metastasis (N0) and 13 N1b PTMCs was performed using primary tumors and matched normal thyroid tissues. RESULTS: The mutational burden was comparable in N0 and N1b tumors, as the median number of mutations was 23 (range, 12 to 46) in N0 and 24 (range, 12 to 50) in N1b PTMC (P=0.918). The most frequent mutations were detected in PGS1, SLC4A8, DAAM2, and HELZ in N1b PTMCs alone, and the K158Q mutation in PGS1 (four patients, Fisher's exact test P=0.041) was significantly enriched in N1b PTMCs. Based on pathway analysis, somatic mutations belonging to the receptor tyrosine kinase-RAS and NOTCH pathways were most frequently affected in N1b PTMCs. We identified four mutations that are predicted to be pathogenic in four genes based on Clinvar and Combined Annotation-Dependent Depletion score: BRAF, USH2A, CFTR, and PHIP. A missense mutation in CFTR and a nonsense mutation in PHIP were detected in N1b PTMCs only, although in one case each. BRAF mutation was detected in both N0 and N1b PTMCs. CONCLUSION: This first comprehensive WES analysis of the mutational landscape of N0 and N1b PTMCs identified pathogenic genes that affect biological functions associated with the aggressive phenotype of PTMC.

Spine-Hip Discordance and FRAX assessment Fracture Risk in Postmenopausal Women with Osteopenia from Concordant Diagnosis Between Lumbar Spine and Femoral Neck.

The diagnostic criteria proposed by the World Health Organization did not consider the discrepancy in diagnosis between lumbar spine (LS) and femoral neck (FN) and the clinical implications is unclear. Therefore, this retrospective study evaluated the probability of fracture risk in postmenopausal women with lumbar spine (LS)-femoral neck (FN) bone mineral density (BMD) discordance or not Patients included 1066 healthy postmenopausal women (median age 55.5 years) who visited our hospital for a health check-up between May 2013 and April 2017. Discordance was defined as a difference of one or two degrees between LS BMD and FN BMD. TBS was calculated from dual energy absorptiometry (DXA) images. Fracture risk was assessed using the Fracture Risk Assessment Tool (FRAX), including TBS-adjusted FRAX Seven hundred and two patients (65.9%) showed concordant LS and FN results, whereas 364 patients (34.1%) exhibited discordance. Normal BMD was found in 519 concordant patients (73.9%). Concordant patients showed significantly higher FRAX scores, including TBS-adjusted FRAX results, than discordant patients with low LS or FN. Furthermore, FRAX results in concordant osteopenia patients were similar to that of osteoporosis patients with osteopenia or a normal result at one site. FRAX and TBS-adjusted FRAX results in concordant osteopenia patients were comparable to that of discordant osteoporosis patients We concluded that patients with colncordant osteopenia in both the FN and LS should be managed in a similar way to patients with discordant osteoporosis.

Effect of tamoxifen with or without gonadotropin-releasing hormone analog on DXA values in women with breast cancer.

The purpose of this study was to compare the changes in DXA values including trabecular bone score (TBS) and bone mineral density (BMD) of lumbar spine (LS) and femur according to the hormone therapies including tamoxifen (TMXF) treatment with or without gonadotropin releasing hormone analog (GnRH analog) in women with breast cancer. We enrolled 119 women with breast cancer who had undergone breast-conserving surgery or mastectomy followed by TMXF treatment for postmenopausal women (TMXF group, n = 63, 52.9%) or by combination therapy of TMXF combined with GnRH analog for premenopausal women (TMXF + GnRH group, n = 56, 47.1%) from December 2013 to December 2017. The median follow-up period was 13 months (interquartile range [IQR], 12.0-14.75) for TMXF group and 13.5 months (IQR, 12.00-16.00) for TMXF + GnRH group, respectively. Patients did not receive bone-modifying therapy. The baseline dual-energy X-ray absorptiometry (DXA) scan before breast cancer surgery and follow-up DXA during hormone therapy. Comparing the first and follow-up DXA results, BMD in LS were significantly decreased in both TMXF (P < 0.001, mean difference: - 0.06) and TMXF + GnRH (P < 0.001, mean difference: - 0.09) groups. BMD values of femoral neck (P = 0.0011, mean difference: - 0.01) and total femur (P < 0.001, mean difference: - 0.03) was significantly changed between the baseline and follow-up DXA in TMXF + RnRH group. In the TMX group, a significant changed occurred in the BMD in total femur (P < 0.001, mean difference: - 0.030) but not the BMD of femoral neck (P = 0.095, mean difference: - 0.007). Regarding TBS, no significant change was found in the TMXF (P = 0.574, mean difference: - 0.004) group, whereas there was a significant decrease in TBS in the TMXF + GnRH (P < 0.001, mean difference: - 0.02) group during follow-up. TBS is more sensitive in reflecting the bone microarchitecture changes by TMXF or GnRH agonist in breast cancer patients than BMD. This finding demonstrates that TBS can be a useful parameter to detect bone microarchitectural changes in clinical applications.

Thyroid cancer after hysterectomy and oophorectomy: a nationwide cohort study.

OBJECTIVE: Little is known about the role of estrogen in thyroid cancer development. We aimed to evaluate the association between hysterectomy or bilateral salpingo-oophorectomy (BSO) and the risk of subsequent thyroid cancer. DESIGN: A nationwide cohort study. METHODS: Data from the Korea National Health Insurance Service between 2002 and 2017 were used. A total of 78 961 and 592 330 women were included in the surgery group and no surgery group, respectively. The surgery group was categorized into two groups according to the extent of surgery: hysterectomy with ovarian conservation (hysterectomy-only) and BSO with or without hysterectomy (BSO). RESULTS: During 8 086 396.4 person-years of follow-up, 12 959 women developed thyroid cancer. Women in the hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) and BSO (adjusted hazard ratio = 1.4, P < 0.001) groups had increased risk of thyroid cancer compared to those in the no surgery group. In premenopausal women, hysterectomy-only (adjusted hazard ratio = 1.7, P < 0.001) or BSO (adjusted hazard ratio = 1.4, P < 0.001) increased the risk of subsequent thyroid cancer, irrespective of hormone therapy, whereas, there was no significant association between hysterectomy-only (P = 0.204) or BSO (P = 0.857) and thyroid cancer development in postmenopausal women who had undergone hormone therapy. CONCLUSIONS: Our findings do not support the hypotheses that sudden or early gradual decline in estrogen levels is a protective factor in the development of thyroid cancer, or that exogenous estrogen is a risk factor for thyroid cancer.

Vascular dysfunction as a potential culprit of sarcopenia.

Aging-related changes to biological structures such as cardiovascular and musculoskeletal systems contribute to the development of comorbid conditions including cardiovascular disease and frailty, and ultimately lead to premature death. Although, frail older adults often demonstrate both cardiovascular and musculoskeletal comorbidities, the etiology of sarcopenia, and especially the contribution of cardiovascular aging is unclear. Aging-related vascular calcification is prevalent in older adults and is a known risk factor for cardiovascular disease and death. The effect vascular calcification has on function during aging is not well understood. Emerging findings suggest vascular calcification can impact skeletal muscle perfusion, negatively affecting nutrient and oxygen delivery to skeletal muscle, ultimately accelerating muscle loss and functional decline. The present review summarizes existing evidence on the biological mechanisms linking vascular calcification with sarcopenia during aging.

Short-term bone marrow suppression in differentiated thyroid cancer patients after radioactive iodine treatment.

After thyroidectomy in differentiated thyroid cancer (DTC), radioactive iodine (RAI) treatment is often used for remnant ablation. However, RAI treatment has been associated with bone marrow suppression, and leukopenia, anemia, and thrombocytopenia may occur after a single RAI administration. In this study, we examined the change in complete blood counts at 1 week after RAI administration; this is less well studied. A group of 189 DTC patients who received RAI treatment and underwent blood tests before and after treatment, were included. Peripheral blood counts at baseline were compared to those obtained at 1 week, 1-6 months, and 6-12 months after RAI treatment in order to test for bone marrow suppression. At 1 week after RAI treatment, there was a significant decrease in the white blood cell count (WBC, 5.8 ± 1.6 × 109/L vs. 5.4 ± 1.5 × 109/L, p < 0.001) and hemoglobin level (Hb, 13.5 ± 1.7 g/dL vs. 13.3 ± 1.4 g/dL, p = 0.001). The WBC decrease was mostly due to lymphocyte counts (2.2 ± 0.6 × 109/L vs. 1.6 ± 0.5 × 109/L, p < 0.001), with no decrease in the neutrophil count. Although not significantly changed at 1 week, platelets counts were altered within 6 months (265 ± 69 × 109/L vs. 239 ± 53 × 109/L, p < 0.001). The decline in the WBC count recovered within 6 months; lymphocyte and platelet counts recovered within 12 months. In conclusion, RAI treatment after a thyroidectomy was associated with a statistically significant but temporary decline in WBC counts and Hb levels at 1 week. Physicians treating DTC patients should not decrease usage of moderate dose RAI treatments.

Association between Serum Free Thyroxine and Anemia in Euthyroid Adults: A Nationwide Study.

BACKGROUND: Studies on the relationship between thyroid function and anemia in the euthyroid range are scarce. We aimed to evaluate the association between anemia and serum free thyroxine (fT4) and thyrotropin (TSH) in euthyroid adults. METHODS: Data on 5,352 participants aged ≥19 years were obtained from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Anemia was defined as hemoglobin (Hb) <13 and <12 g/dL for men and women, respectively. RESULTS: Overall, 6.1% of participants had anemia, and more women (9.9%) had anemia than men (2.8%, P<0.001). In multivariate analysis, serum fT4 levels, but not TSH, were positively associated with serum Hb levels in both sexes (P<0.001, each). Serum Hb levels linearly reduced across decreasing serum fT4 quartile groups in both sexes (P<0.001, each). After adjusting for potential confounding factors, participants with low-normal fT4 had 4.4 (P=0.003) and 2.8 times (P<0.001) higher risk for anemia than those with high-normal fT4 among men and women, respectively. When participants were divided into two groups at 50 years of age, in younger participants, men and women with the first quartile were at higher risk of anemia than men with the second quartile (odds ratio [OR], 3.3; P=0.029) and women with the forth quartile (OR, 3.2; P<0.001), respectively. This association was not observed in older participants. CONCLUSION: These results suggest that a low-normal level of serum fT4 was associated with a lower serum Hb level and a higher risk of anemia in euthyroid adults, especially in younger participants.

Combined Aerobic and Resistance Exercise Training Reduces Circulating Apolipoprotein J Levels and Improves Insulin Resistance in Postmenopausal Diabetic Women.

BACKGROUND: Circulating apolipoprotein J (ApoJ) is closely associated with insulin resistance; however, the effect of exercise on circulating ApoJ levels and the association of ApoJ with metabolic indices remain unknown. Here, we investigated whether a combined exercise can alter the circulating ApoJ level, and whether these changes are associated with metabolic indices in patients with type 2 diabetes mellitus. METHODS: Postmenopausal women with type 2 diabetes mellitus were randomly assigned into either an exercise (EXE, n=30) or control (CON, n=15) group. Participants in the EXE group were enrolled in a 12-week program consisting of a combination of aerobic and resistance exercises. At baseline, 4, 8, and 12 weeks, body composition and metabolic parameters including homeostatic model assessment of insulin resistance (HOMA-IR) and serum ApoJ levels were assessed. RESULTS: In the EXE group, ApoJ levels decreased 26.3% and 19.4%, relative to baseline, at 8 and 12 weeks, respectively. Between-group differences were significant at 8 and 12 weeks (P<0.05 and P<0.001, respectively). In the EXE group, 12 weeks of exercise resulted in significant decreases in body weight, percent body fat, and HOMA-IR indices. Concurrently, weight-adjusted appendicular skeletal muscle mass (ASM/wt) was increased in the EXE group compared with the CON group. Importantly, changes in the ApoJ level were significantly correlated with changes in ASM/wt. CONCLUSION: Exercise training resulted in a significant decrease in the circulating ApoJ level, with changes in ApoJ associated with an improvement in some insulin resistance indices. These data suggest that circulating ApoJ may be a useful metabolic marker for assessing the effects of exercise on insulin resistance.

Effect of sex hormones on extracellular matrix of lamina propria in rat vocal fold.

OBJECTIVES: The role of sex hormones for voice changes in men and women is presently unknown. To determine the effect of sex hormone on the vocal fold, changes of the extracellular matrix (ECM) in vocal fold lamina propria were assessed in orchiectomized (ORX) and ovariectomized (OVX) rats. METHODS: Male and female Sprague-Dawley rats were divided into sham-operated control male (CON-ORX), ORX, sham-operated female (CON-OVX), and OVX rats. Histological changes and expression of ECM-related genes in lamina propria of the vocal fold were evaluated at 4 and 12 weeks after surgery. RESULTS: Testosterone and estradiol levels decreased in the ORX and OVX groups, respectively. ORX groups did not have significant changes compared with CON-ORX groups. However, the expression of hyaluronic acid (HA) was decreased in the OVX group compared with the CON-OVX group. The expression of collagen I in OVX was lower than in the CON-OVX group. Collagen III levels were elevated at 4 weeks in the OVX group, but collagen III levels were diminished at 12 weeks in the OVX group. Expression of elastin in the ECM was less dense in the OVX group compared with controls. The expression MMP-1 and MMP-9 showed significantly increase in the OVX group compared to the CON-OVX group. CONCLUSION: No changes of the ECM-related genes in the vocal fold lamina propria were observed in ORX groups with reduced testosterone. However, changes of several ECM-related genes were observed in OVX groups with decreased estrogen. These results indicate that the vocal fold is an estrogen-sensitive target organ and that decreased estrogen, not testosterone, can affect the expression of several ECM-related molecules of vocal fold. LEVEL OF EVIDENCE: NA Laryngoscope, 130:732-740, 2020.

High neutrophil-to-lymphocyte ratio is associated with relapse in Graves' disease after antithyroid drug therapy.

PURPOSE: Antithyroid drugs (ATDs) are effective in controlling hyperthyroidism due to Graves' disease (GD); however, long-term remission rates are low. The neutrophil-to-lymphocyte ratio (NLR) is a useful prognostic marker in many inflammatory diseases. We aimed to evaluate whether NLR can be used as a prognostic marker for relapse in patients with GD after ATD therapy. METHODS: This retrospective cohort study included 108 patients with newly diagnosed GD who achieved remission after ATD therapy and were followed-up for >12 months after ATD discontinuation. The primary outcome was relapse-free survival (RFS). RESULTS: Patients were classified into two groups according to baseline NLR: low NLR group with NLR < 1.14 (n = 59; 55%) and high NLR group with NLR ≥ 1.14 (n = 49; 45%). During the median follow-up of 6.5 years, disease relapse after a year of ATD withdrawal occurred in 23 (21%) patients. The patients with high NLR had poorer RFS than those with low NLR, and RFS curves were significantly different between the two groups (p = 0.002). In multivariate analysis, a high NLR (OR = 4.22, p = 0.016) was an independent prognostic factor for relapse in patients with GD after adjusting for age, sex, goiter, orbitopathy, thyroid hormone levels, thyrotropin binding inhibiting immunoglobulin titer, and the duration of ATD therapy. CONCLUSIONS: This study showed that NLR can be an early and cost-effective prognostic biomarker for relapse in patients with GD after ATD therapy. Further studies are needed to validate the prognostic role of NLR in GD.