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One of the notable adverse effects of sodium-glucose cotransporter 2 (SGLT2) inhibitor is diabetic ketoacidosis (DKA) often characterized by euglycemia. In this retrospective review of patients with DKA from 2015 to 2023, 21 cases of SGLT2 inhibitorassociated DKA were identified. Twelve (57.1%) exhibited euglycemic DKA (euDKA) while nine (42.9%) had hyperglycemic DKA (hyDKA). More than 90% of these cases were patients with type 2 diabetes mellitus. Despite similar age, sex, body mass index, and diabetes duration, individuals with hyDKA showed poorer glycemic control and lower C-peptide levels compared with euDKA. Renal impairment and acidosis were worse in the hyDKA group, requiring hemodialysis in two patients. Approximately one-half of hyDKA patients had concurrent hyperosmolar hyperglycemic state. Common symptoms included nausea, vomiting, general weakness, and dyspnea. Seizure was the initial manifestation of DKA in two cases. Infection and volume depletion were major contributors, while carbohydrate restriction and inadequate insulin treatment also contributed to SGLT2 inhibitor-associated DKA. Despite their beneficial effects, clinicians should be vigilant for SGLT2 inhibitor risk associated with DKA.
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While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment.
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Antitiroideos , Microbioma Gastrointestinal , Enfermedad de Graves , Humanos , Enfermedad de Graves/tratamiento farmacológico , Enfermedad de Graves/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Adulto , Antitiroideos/uso terapéutico , Persona de Mediana Edad , Heces/microbiología , Estudios de Casos y ControlesRESUMEN
CONTEXT: Thyrotoxicosis requires accurate and expeditious differentiation between Graves' disease (GD) and thyroiditis to ensure effective treatment decisions. OBJECTIVE: This study aimed to develop a machine learning algorithm using ultrasonography and Doppler images to differentiate thyrotoxicosis subtypes, with a focus on GD. METHODS: This study included patients who initially presented with thyrotoxicosis and underwent thyroid ultrasonography at a single tertiary hospital. A total of 7,719 ultrasonography images from 351 patients with GD and 2,980 images from 136 patients with thyroiditis were used. Data augmentation techniques were applied to enhance the algorithm's performance. Two deep learning models, Xception and EfficientNetB0_2, were employed. Performance metrics such as accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and F1 score were calculated for both models. Image pre-processing, neural network model generation, and neural network training results verification were performed using DEEP:PHI® platform. RESULTS: The Xception model achieved 84.94% accuracy, 89.26% sensitivity, 73.17% specificity, 90.06% PPV, 71.43% NPV, and an F1 score of 89.66 for the diagnosis of GD. The EfficientNetB0_2 model exhibited 85.31% accuracy, 90.28% sensitivity, 71.78% specificity, 89.71% PPV, 73.05% NPV, and an F1 score of 89.99. CONCLUSION: Machine learning models based on ultrasound and Doppler images showed promising results with high accuracy and sensitivity in differentiating GD from thyroiditis.
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BACKGRUOUND: There is debate about ultrasonography screening for thyroid cancer and its cost-effectiveness. This study aimed to evaluate the cost-effectiveness of early screening (ES) versus symptomatic detection (SD) for differentiated thyroid cancer (DTC) in Korea. METHODS: A Markov decision analysis model was constructed to compare the cost-effectiveness of ES and SD. The model considered direct medical costs, health outcomes, and different diagnostic and treatment pathways. Input data were derived from literature and Korean population studies. Incremental cost-effectiveness ratio (ICER) was calculated. Willingness-to-pay (WTP) threshold was set at USD 100,000 or 20,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address uncertainties of the model's variables. RESULTS: In a base case scenario with 50 years of follow-up, ES was found to be cost-effective compared to SD, with an ICER of $2,852 per QALY. With WTP set at $100,000, in the case with follow-up less than 10 years, the SD was cost-effective. Sensitivity analysis showed that variables such as lobectomy probability, age, mortality, and utility scores significantly influenced the ICER. Despite variations in costs and other factors, all ICER values remained below the WTP threshold. CONCLUSION: Findings of this study indicate that ES is a cost-effective strategy for DTC screening in the Korean medical system. Early detection and subsequent lobectomy contribute to the cost-effectiveness of ES, while SD at an advanced stage makes ES more cost-effective. Expected follow-up duration should be considered to determine an optimal strategy for DTC screening.
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Análisis Costo-Beneficio , Detección Precoz del Cáncer , Años de Vida Ajustados por Calidad de Vida , Neoplasias de la Tiroides , Ultrasonografía , Humanos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/economía , Neoplasias de la Tiroides/diagnóstico , República de Corea/epidemiología , Detección Precoz del Cáncer/economía , Detección Precoz del Cáncer/métodos , Ultrasonografía/economía , Ultrasonografía/métodos , Estudios Retrospectivos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Cadenas de MarkovRESUMEN
CONTEXT: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption. OBJECTIVE: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data. DESIGN/SETTING/PARTICIPANTS: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study. RESULTS: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study. CONCLUSION: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function.
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BACKGRUOUND: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. METHODS: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0-4), and the sum of quartiles (0-12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. RESULTS: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. CONCLUSION: Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.
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Enfermedades Cardiovasculares , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Factores de Riesgo , gamma-Glutamiltransferasa , Guanosina TrifosfatoRESUMEN
Objective: Real-world-based population data about the optimal low-density lipoprotein cholesterol (LDL-C) level for preventing cardiovascular disease in very high-risk populations is scarce. Methods: From 2009 to 2012, 26,922 people aged ≥ 40 years with type 2 diabetes mellitus (T2DM) who had a history of percutaneous coronary intervention (PCI) were analyzed. Data from the Korean National Health Insurance System were used. They were followed up to the date of a cardiovascular event or the time to death, or until December 31, 2018. Endpoints were recurrent PCI, newly stroke or heart failure, cardiovascular death, and all-cause death. Participants were divided into the following categories according to LDL-C level: <55 mg/dL, 55-69 mg/dL, 70-99 mg/dL, 100-129 mg/dL, 130-159 mg/dL, and ≥ 160 mg/dL. Results: Compared to LDL-C < 55 mg/dL, the hazard ratios (HR) for re-PCI and stroke increased linearly with increasing LDL-C level in the population < 65 years. However, in ≥ 65 years old, HRs for re-PCI and stroke in LDL-C = 55-69 mg/dL were 0.97 (95% CI: 0.85-1.11) and 0.96 (95% CI: 0.79-2.23), respectively. The optimal range with the lowest HR for heart failure and all-cause mortality were LDL-C = 70-99 mg/dL and LDL-C = 55-69 mg/dL, respectively, in all age groups (HR: 0.99, 95% CI: 0.91-1.08 and HR: 0.91, 95% CI: 0.81-1.01). Conclusion: LDL-C level below 55 mg/dL appears to be optimal in T2DM patients with established cardiovascular disease aged < 65 years, while an LDL-C level of 55-69 mg/dL may be optimal for preventing recurrent PCI and stroke in patients over 65 years old.
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BACKGROUND: Recently, active surveillance (AS) has been introduced as an alternative to early surgery (ES) for the management of papillary thyroid microcarcinoma (PTMC), because of its indolent features and low mortality. However, its cost effects have not been determined and the findings of current studies differ, according to each country's medical system. METHODS: A Markov model was constructed to compare the cost-effectiveness of AS and ES, based on a reference case of a 40-year-old patient diagnosed with PTMC. Costs and transition probabilities were derived from previous clinical studies in Korean populations, and the incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were calculated. The willingness-to-pay (WTP) threshold was set at USD 100,000 per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted to address the uncertainties in the model's variables. RESULTS: From the base scenario, the cumulative costs and effectiveness were both higher in ES than AS. The ICER for ES, compared with AS, was USD 6,619.86/QALY, lower than the set WTP. The NMB difference between AS and ES increased across the stages (USD 5,980 at the first stage and USD 159,667 at the last stage). The ICER increased along with decreasing age and increasing cost of surgery. The higher the ES utility score and the lower that of AS, the more cost-effective ES, with WTP set at USD 30,000. CONCLUSION: In the current Korean medical system, ES is more cost-effective than AS. ES is more cost-effective as it is diagnosed at young age and followed-up for a long time.
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Neoplasias de la Tiroides , Espera Vigilante , Humanos , Adulto , Cáncer Papilar Tiroideo/cirugía , Estudios Retrospectivos , Análisis Costo-Beneficio , Neoplasias de la Tiroides/cirugía , República de CoreaRESUMEN
BACKGRUOUND: To determine whether baseline thyroid-stimulating immunoglobulin (TSI) bioassay or its early response upon treatment with an anti-thyroid drug (ATD) can predict prognosis of Graves' disease (GD) in real-world practice. METHODS: This retrospective study enrolled GD patients who had previous ATD treatment with TSI bioassay checked at baseline and at follow-up from April 2010 to November 2019 in one referral hospital. The study population were divided into two groups: patients who experienced relapse or continued ATD (relapse/persistence), and patients who experienced no relapse after ATD discontinuation (remission). The slope and area under the curve at 1st year (AUC1yr) of thyroid-stimulating hormone receptor antibodies including TSI bioassay and thyrotropin-binding inhibitory immunoglobulin (TBII) were calculated as differences between baseline and second values divided by time duration (year). RESULTS: Among enrolled 156 study subjects, 74 (47.4%) had relapse/persistence. Baseline TSI bioassay values did not show significant differences between the two groups. However, the relapse/persistence group showed less decremental TSI bioassay in response to ATD than the remission group (-84.7 [TSI slope, -198.2 to 8.2] vs. -120.1 [TSI slope, -204.4 to -45.9], P=0.026), whereas the TBII slope was not significantly different between the two groups. The relapse/persistence group showed higher AUC1yr of TSI bioassay and TBII in the 1st year during ATD treatment than the remission group (AUC1yr for TSI bioassay, P=0.0125; AUC1yr for TBII,
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Enfermedad de Graves , Receptores de Tirotropina , Humanos , Estudios Retrospectivos , Autoanticuerpos , Inmunoglobulinas Estimulantes de la Tiroides/uso terapéutico , Enfermedad de Graves/tratamiento farmacológico , Pronóstico , BioensayoRESUMEN
Recently, selpercatinib, a highly selective inhibitor of RET receptor tyrosine kinase, has been used for RET-altered thyroid cancer. We present four cases of patients with advanced thyroid cancer who were treated with selpercatinib. The first patient was a 63-year-old male with advanced medullary thyroid cancer (MTC) treated with vandetanib. Six months ago, he had an intracranial hemorrhage and swallowing difficulty. He started selpercatinib with percutaneous endoscopic gastrostomy (PEG). For 11 months, a partial response (PR) was observed stably with PEG administration without any more cardiovascular events. The second patient was a 67-year-old female with advanced MTC treated with vandetatib. After selpercatinib treatment, a PR was observed for most metastatic sites, including choroidal metastasis. The third patient was a 32-year-old female with advanced papillary thyroid cancer (PTC) without history of systematic treatment. For six months, a PR was observed at her metastatic site with manageable adverse events. The last patient was a 59-year-old female with advanced PTC treated with lenvatinib. She suffered from a panic disorder and pleural pain due to metastasis during lenvatinib treatment. After selpercatinib treatment, her pain and panic symptoms were improved. Facing varying clinical obstacles of the real world, selpercatinib safely proved remarkable therapeutic efficacy regardless of previous treatment or metastatic site.
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Adenocarcinoma , Antineoplásicos , Neoplasias de la Tiroides , Masculino , Femenino , Humanos , Adulto , Anciano , Persona de Mediana Edad , Antineoplásicos/efectos adversos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Adenocarcinoma/tratamiento farmacológico , República de Corea , Proteínas Proto-Oncogénicas c-retRESUMEN
BACKGRUOUND: The prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications. METHODS: In this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends. RESULTS: The fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; p=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant. CONCLUSION: YOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Adulto , Edad de Inicio , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Glucosa , Control Glucémico , Humanos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Differential diagnosis of thyrotoxicosis is essential because therapeutic approaches differ based on disease etiology. We aimed to perform differential diagnosis of thyrotoxicosis using machine learning algorithms with initial laboratory findings. This is a retrospective study through medical records. Patients who visited a single hospital for thyrotoxicosis from June 2016 to December 2021 were enrolled. In total, 230 subjects were analyzed: 124 (52.6%) patients had Graves' disease, 65 (28.3%) suffered from painless thyroiditis, and 41 (17.8%) were diagnosed with subacute thyroiditis. In consideration that results for the thyroid autoantibody test cannot be immediately confirmed, two different models were devised: Model 1 included triiodothyronine (T3), free thyroxine (FT4), T3 to FT4 ratio, erythrocyte sediment rate, and C-reactive protein (CRP); and Model 2 included all Model 1 variables as well as thyroid autoantibody test results, including thyrotropin binding inhibitory immunoglobulin (TBII), thyroid-stimulating immunoglobulin, anti-thyroid peroxidase antibody, and anti-thyroglobulin antibody (TgAb). Differential diagnosis accuracy was calculated using seven machine learning algorithms. In the initial blood test, Graves' disease was characterized by increased thyroid hormone levels and subacute thyroiditis showing elevated inflammatory markers. The diagnostic accuracy of Model 1 was 65-70%, and Model 2 accuracy was 78-90%. The random forest model had the highest classification accuracy. The significant variables were CRP and T3 in Model 1 and TBII, CRP, and TgAb in Model 2. We suggest monitoring the initial T3 and CRP levels with subsequent confirmation of TBII and TgAb in the differential diagnosis of thyrotoxicosis.
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Objective: Thyroid-stimulating immunoglobulin (TSI) bioassay has a better ability to predict the relapse rate of Graves' disease (GD) than the thyroid-stimulating hormone (TSH)-binding inhibitory immunoglobulin method in terms of measuring the TSH receptor antibody. However, the optimal TSI bioassay cutoff for predicting relapse after antithyroid drug (ATD) withdrawal is not well evaluated. Methods: This retrospective study enrolled GD patients who had been treated with ATD and obtained their TSI bioassay <140% from January 2010 to December 2019 in a referral hospital. Results: Among 219 study subjects, 86 patients (39.3%) experienced relapse. The TSI bioassay value of 66.5% significantly predicted the relapse of GD (Pâ =â 0.049). The group with a TSI bioassay valueâ >â 66.5% were expected to show a 23.8% relapse rate at 2 from ATD withdrawal, and the group with a TSIâ <â 66.5% had a 12.7% relapse rate based on Kaplan-Meier curves analysis. The TSI bioassay showed a good ability to predict relapse GD in the female group (Pâ =â 0.041) but did not in the male group (Pâ =â 0.573). The risk scoring based on the nomogram with risk factors for GD relapse, which was constructed to overcome the limitation, increased the predictive ability of GD relapse by 11.5% compared to the use of the TSI bioassay alone. Conclusions: The cutoff value of the TSI bioassay to predict GD relapse should be lower than that for diagnosing GD. However, as the single use of the TSI bioassay has limitations, a nomogram with multiple risk factors including TSI bioassay could be helpful to predict GD relapse.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. METHODS: Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary's Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. RESULTS: Among the 191 patients, 64 (33.5%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (25 months vs. 18 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.480 (p = 0.006). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for mortality of 0.324 (p = 0.002). Patients with thyrotoxicosis showed a worse hazard ratio for mortality than those without thyroid irAE, although the difference was not statistically significant. CONCLUSIONS: It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.
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Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Pronóstico , Estudios Retrospectivos , Glándula Tiroides/patologíaRESUMEN
BACKGROUND: Microvascular ultrasonography (MVUS) is a third-generation Doppler technique that was developed to increase sensitivity compared to conventional Doppler. The purpose of this study was to compare MVUS with conventional color Doppler (CD) and power Doppler (PD) imaging to distinguish Graves' disease (GD) from destructive thyroiditis (DT). METHODS: This prospective study included 101 subjects (46 GDs, 47 DTs, and eight normal controls) from October 2020 to November 2021. All ultrasonography examinations were performed using microvascular flow technology (MV-Flow). The CD, PD, and MVUS images were semi-quantitatively graded according to blood flow patterns. On the MVUS images, vascularity indices (VIs), which were the ratio (%) of color pixels in the total grayscale pixels in a defined region of interest, were obtained automatically. Receiver operating characteristic curve analysis was performed to verify the diagnostic performance of MVUS. The interclass correlation coefficient and Cohen's kappa analysis were used to analyze the reliability of MVUS (ClinicalTrials.gov:NCT04879173). RESULTS: The area under the curve (AUC) for CD, PD, MVUS, and MVUS-VI was 0.822, 0.844, 0.808, and 0.852 respectively. The optimal cutoff value of the MVUS-VI was 24.95% for distinguishing GD and DT with 87% sensitivity and 80.9% specificity. We found a significant positive correlation of MVUS-VI with thyrotropin receptor antibody (r=0.554) and with thyroid stimulating immunoglobulin bioassay (r=0.841). MVUS showed high intra- and inter-observer reliability from various statistical method. CONCLUSION: In a real time and quantitative manner, MVUS-VI could be helpful to differentiate GD from thyroiditis in thyrotoxic patients, with less inter-observer variability.
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Enfermedad de Graves , Tiroiditis , Enfermedad de Graves/diagnóstico por imagen , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Tiroiditis/diagnóstico por imagen , UltrasonografíaRESUMEN
BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) ligands have been widely shown to correlate with epithelial-mesenchymal transition (EMT) and cancer progression. Lobeglitazone (LGZ) is a novel ligand of PPAR-γ; and its role in EMT and metastasis in papillary thyroid carcinoma (PTC) is poorly understood. We aimed to investigate the role of LGZ in metastatic behavior of PTC cells. METHODS: Half maximal inhibitory concentration (IC50) values of LGZ in BRAF-mutated PTC cell lines (BCPAP and K1) were determined using MTT assay. Rosiglitazone (RGZ), the PPAR-γ ligand was used as a positive control. The protein expression of PPAR-γ, cell-surface proteins (E-cadherin, N-cadherin), cytoskeletal protein (Vimentin), transcription factor (Snail), p38 mitogenactivated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) 1/2 pathway, and matrix metalloproteinase (MMP)-2 expression were measured using Western blotting. Changes in E-cadherin expression were also determined using immunocytochemistry. Cell migration and invasion were analyzed using wound healing and Matrigel invasion assays. RESULTS: Treatment with LGZ or RGZ significantly inhibited transforming growth factor-beta1 (TGF-ß1)-induced EMT-associated processes such as fibroblast-like morphological changes, EMT-related protein expression, and increased cell migration and invasion in BCPAP and K1 cells. LGZ restored TGF-ß1-induced loss of E-cadherin, as observed using immunocytochemistry. Furthermore, LGZ and RGZ suppressed TGF-ß1-induced MMP-2 expression and phosphorylation of p38 MAPK, but not ERK1/2. Although there was no change in PPAR-γ expression after treatment with LGZ or RGZ, the effect of downstream processes mediated by LGZ was hampered by GW9662, a PPAR-γ antagonist. CONCLUSION: LGZ inhibits TGF-ß1-induced EMT, migration, and invasion through the p38 MAPK signaling pathway in a PPAR-γ-dependent manner in PTC cells.
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Transición Epitelial-Mesenquimal/efectos de los fármacos , PPAR gamma , Pirimidinas , Tiazolidinedionas , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Movimiento Celular/efectos de los fármacos , Humanos , PPAR gamma/agonistas , Pirimidinas/farmacología , Transducción de Señal , Tiazolidinedionas/farmacología , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
PURPOSE: Studies investigating the association between vitamin D and metabolic parameters have reported inconsistent results depending on the characteristics of the subjects. We aimed to investigate the association between vitamin D levels and various metabolic indicators in healthy Korean adults by using nationally representative data. METHODS: A total of 3640 participants were included after excluding subjects who were ≤19 years of age and had a history of treatment for dyslipidemia, hypertension, or diabetes and a history of other chronic diseases such as liver and kidney diseases. After dividing the 25-hydroxyvitamin D (25(OH)D) level into quartiles, the risk of having each metabolic parameter higher than the median value was determined according to the 25(OH)D quartile by using regression analysis. RESULTS: In a multivariate regression analysis, a higher 25(OH)D quartile tended to have a significantly lower risk of having a triglyceride (TG) level higher than the median value (103.1 mg/dl). As the quartile increased, the risk of having a waist circumference or body mass index higher than the median value also decreased, but the difference was not statistically significant. No significant changes were observed in fasting glucose or glycated hemoglobin level according to quartile. CONCLUSION: We demonstrated that subjects with a higher 25(OH)D quartile exhibited a significantly lower risk of having a TG level higher than the median value in a representative Korean population. More evidence from a prospective study on whether vitamin D supplementation improves serum TG levels in healthy adults is needed.
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Papillary thyroid microcarcinoma (PTMC) has indolent features and low mortality. Recently, active surveillance (AS) instead of early surgery (ES) has been introduced as one treatment option but economical preference has not been established. The study objective was to systemically review the literature relating to cost-effectiveness of AS compared to ES for PTMC. Keywords were selected through PICO (Population, Intervention, Comparison, and Outcomes) tools. The search was conducted using PubMed, Cochrane, EMBASE, and Elsevier databases. Papers that had irrelevant titles were written in foreign languages, or had no original results were excluded. Out of the 62 papers extracted, five relevant to the subject matter of this study were identified. Three papers made their own decision models and proceeded with cost-effectiveness analysis (CEA), but the remaining two simply compared costs rather than cost-effectiveness. In terms of cost-effectiveness, three papers preferred AS, one preferred ES, and one preferred neither. The major differences in the CEA might arise from variations in each country's medical insurance system, the utility score systems, and decision models used. In subgroup analysis, two papers preferred AS to ES for patients at a younger age at diagnosis in terms of cost-effectiveness as well as tumor biological characteristics. Although AS has been generally more cost-effective than ES in previous publications, younger age at diagnosis could be one factor contributing to preference for ES. The CEA of prospective cohorts based on the decision model and utility score for thyroid cancer should be undertaken to confirm the cost-effectiveness of AS.