Combining CEUS and ultrasound parameters in thyroid nodule and cancer diagnosis: a TIRADS-based evaluation.

Contrast-enhanced ultrasonography (CEUS) has been established as a diagnostic tool for assessing microvascularization, essential for understanding angiogenesis in neoplastic development. AIM: This study assesses the effectiveness of CEUS as a supplementary tool to TIRADS in enhancing the ultrasound-based diagnosis of thyroid cancer. METHODS AND MATERIALS: Over one year, 157 nodules in 133 patients, with predominantly solid thyroid nodules, were examined using ultrasound and CEUS and underwent thyroidectomy, allowing for a comparison of ultrasound findings with pathological reports. RESULTS: Thyroid cancer was identified in 31.21% (49/157) of cases. Significant CEUS high-risk features included inhomogeneous enhancement, enhancement defects, and complete hypoenhancement (AUC 0.818, 0.767, 0.864 respectively). Nodules exhibiting any of these features were classified as high-risk in CEUS. The diagnostic performance of TIRADS improved when combined with CEUS, with AUC increasing from 0.707 to 0.840 and improved sensitivity. CONCLUSION: The integration of CEUS with TIRADS significantly enhances the diagnostic accuracy and specificity in identifying thyroid cancer. This combination proves to be a more effective method for risk stratification and diagnosis, highlighting the value of CEUS as an adjunctive tool in thyroid cancer evaluation.

Impact of ultrasound elastography in evaluating Bethesda category IV thyroid nodules with histopathological correlation.

Introduction: Fine needle aspiration (FNA) is the gold standard method recommended in the diagnosis of thyroid nodules. Bethesda IV cytology results are identified in 7-9% of nodules investigated through FNA, with reported malignancy rate in a wide range of 10-40%. The recommended treatment is either surgical or risk additional molecular testing before surgery. However, a large number of nodules belonging to this category (60-80%) are observed to be benign after surgical excision, which can put the patient at risk of unnecessary surgical morbidity. This study aimed to assess the diagnostic performance of conventional ultrasound, the ACR TI-RADS score and elastography in cases of Bethesda IV cytology on FNA. Methods: We evaluated ninety-seven consecutive cases with Bethesda category IV results on FNA by using conventional B-mode ultrasound, qualitative strain or shear-wave elastography (Hitachi Preirus Machine, Hitachi Inc., Japan and Aixplorer Mach 30 Supersonic Imagine, Aix-en-Provence, France) and all nodules were classified according to the ACR TI-RADS system. Conventional ultrasound was used to categorize the nodules as potentially malignant based on the following features: hypoechogenicity, inhomogeneity, a taller than wide shape, irregular margins, presence of microcalcifications, an interrupted thyroid capsule and suspicious cervical lymph nodes. Elastography classified nodules with increased stiffness as suspicious for malignancy. Results: We considered pathology results as the gold standard diagnosis, finding that 32 out of 97 nodules were carcinomas (33%) and 65 out of 97 were benign nodules (67%). The benign group included twenty cases of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Finally, we compared ultrasound data with pathology results, which showed that nineteen out of the 32 malignant nodules presented with increased stiffness on elastography (p=0.0002). On conventional ultrasound, we found that microcalcifications (p=0.007), hypoechogenicity and irregular margins (p=0.006) are features which can distinguish between benign and malignant nodules with statistical significance. Discussion: Integrating elastography as a parameter of the ACR TI-RADS score in the evaluation of Bethesda category IV nodules showed a sensitivity of 90.62% in detecting thyroid cancer cases (p=0.006). We can conclude that elastographic stiffness as an addition to high risk features observed on conventional ultrasound improves the detection of malignant nodules in cases with Bethesda IV cytology.

Breast Cancer Risk Factors among Women with Solid Breast Lesions.

BACKGROUND: Breast cancer is the most frequent malignancy in women worldwide and one of the most curable cancers if diagnosed at an early stage. Female patients presenting solid breast lesions are greatly predisposed to breast cancer development, and as such, effective screening of high-risk patients is valuable in early-stage breast cancer detection. OBJECTIVES: The aim of our study was to identify the most relevant demographic, reproductive and lifestyle risk factors for breast cancer among women with solid breast lesions living in western Romania, namely the urban region consisting of Timisoara and the rural surrounding regions. METHODS: From January 2017 to December 2021, 1161 patients with solid breast lesions, as detected by sonoelastography, were divided into two groups: patients with benign lesions (1019, 87.77%) and patients with malignant nodules (142, 12.23%). The malignancy group was confirmed by a histopathological result. Variables including age, BMI, menarche, menopause, years of exposure to estrogen, number of births, breastfeeding period, use of oral combined contraceptives, smoker status, family medical history and living area (rural-urban) were recorded. RESULTS: It was evidenced by our study that the main risk factors for malignancy were elevated age (OR = 1.07, 95% CI 1.05-1.08), BMI (OR = 1.06, 95% CI 1.02-1.10), living area (rural) (OR = 1.86, 95% CI 1.13-2.85) and family medical history (negative) (OR 3.13, 95% CI 1.43-8.29). The other proposed risk factors were not found to be statistically significant. CONCLUSIONS: Age and BMI were observed to be the most significant factors for breast cancer risk increase, followed by living in a rural area. A family history of breast cancer was shown to be inversely correlated with cancer risk increase.

Differentiating thyroid nodules parathyroid lesions using 2D-shear-wave elastography: a novel approach for enhanced diagnostic accuracy.

Differentiating between thyroid and parathyroid lesions by means of ultrasound can be a challenge in some cases. This study explores the diagnostic efficacy of bidimensional shear wave elastography planewave ultrasound (2D SWE PLUS) as an auxiliary technique in distinguishing these superficial structures. We evaluated 86 cases, presenting with concurrent thyroid nodules and hyperparathyroidism, through conventional ultrasound and 2D SWE PLUS, employing an Aixplorer Supersonic Mach30 with a 5-18 MHz linear probe. Statistically significant differences were observed for the elasticity index (EI) between parathyroid and normal thyroid tissue (p<0.0001, U=291), and between parathyroid lesions and thyroid nodules (p<0.0001, U=248.5). An area under the curve (AUC) of 0.961, with an optimal cut-off value of ≤8.9 kPa, was established to effectively distinguish parathyroid tissue from normal thyroid tissue (sensitivity of 91.9%; specificity of 97.5%). Furthermore, an AUC of 0.963 and an optimal cut-off of 9.24 kPa (sensitivity of 94.2%, specificity of 91.1%) were determined for parathyroid vs thyroid lesions. Elasticity values were significantly elevated in the cancer group compared to benign thyroid nodules (p<0.0001). Our findings suggest that 2D SWE PLUS is an effective tool in differentiating between thyroid nodules and parathyroid lesions, enhancing diagnostic performance in neck ultrasonography.

The impact of the COVID-19 pandemic on thyroid nodular disease: a retrospective study in a single center in the western part of Romania.

Introduction: The COVID-19 pandemic had a significant impact on the healthcare system, leading to a prioritization of hospital admissions in many countries. Romania was no exception, and it had to restrict patient access to medical services in hospitals with chronic diseases and oncological pathology, including thyroid cancer. This study aimed to compare the clinical and pathological factors of patients with nodular thyroid disease diagnosed and surgically treated during the two years before and after the COVID-19 pandemic, in a single medical institution. Methods: The retrospective study included 1505 patients who were diagnosed and operated on for nodular thyroid disease between January 2018 and December 2021. The patients were divided into two groups: the "PRECOVID" group (January 2018 to February 2020), and the "POSTCOVID" group (March 2020 to December 2021). The analyzed parameters included patients' gender, age, preoperative diagnosis, type of surgical intervention, and pathological diagnosis. Results: A significant decrease was observed in the number of surgeries performed for thyroid nodular disease during the COVID-19 pandemic period (450 versus 1055 cases, p<0.00001). There was a significant decrease in the number of surgical reinterventions (0.9% in the POSTCOVID group versus 2.9% in the PRECOVID group, p=0.01) and a significant increase in the number of total thyroidectomies (84.9% in the POSTCOVID group versus 80.1% in the PRECOVID group, p=0.02). We also observed a higher incidence of malignant/borderline tumors in the POSTCOVID group compared to the PRECOVID group (p=0.04) and a significantly higher frequency of aggressive forms of thyroid cancer in the POSTCOVID group (p=0.0006). Discussion: The COVID-19 pandemic had a significant impact on the surgical management of nodular thyroid disease, resulting in a decrease in surgeries and a change in the type of surgical interventions performed. The higher incidence of malignant/borderline tumors diagnosed during the pandemic highlights the importance of timely diagnosis and treatment of thyroid nodules to prevent cancer progression.

The Oscillometric Pulse Wave Analysis Is Useful in Evaluating the Arterial Stiffness of Obese Children with Relevant Cardiometabolic Risks.

Early detection of all complications of childhood obesity is imperative in order to minimize effects. Obesity causes vascular disruptions, including early increased arterial stiffness and high blood pressure. This study's aim is to assess the reliability of pulse wave analysis (PWA) in obese children and how additional risk factors influence the evaluated parameters. We analyzed 55 children aged 6-18 years old by measuring their pulse wave velocity (PWV), augmentation index (AIx), peripheral blood pressure (SBP, DBP), heart rate, central blood pressure (cSBP, cDBP) and central pulse pressure (cPP). We used the oscillometric IEM Mobil-O-Graph and performed a single-point brachial measurement. The subjects were divided into two groups: obese (n = 30) and normal-weight (n = 25) and were clinically and anamnestically assessed. BMI and waist circumference are significantly correlated to higher values for PWV, SBP, DBP, cSBP, and cDBP. Weight significantly predicts PWV, SBP, DBP and cPP. The risk factors that significantly influence the PWA and BP values are: a cardiometabolically risky pregnancy (higher PWV, AIx, SBP), active and passive smoking (higher PWV, SBP, cSBP, cDBP), sleep deprivation (higher PWV, SBP, cSBP) and sedentariness (higher PWV, AIx, peripheral and central BP). We conclude that obese children with specific additional cardiometabolic risk factors present increased arterial stiffness and higher blood pressure values.

Vitamin D Status and Steatohepatitis in Obese Diabetic and Non-Diabetic Patients.

BACKGROUND AND AIMS: The presence of steatohepatitis in obese patients can be multifactorial. The current study tries to determine the differences between diabetic and non-diabetic patients regarding the presence of steatohepatitis. We evaluated sequential liver samples and collected the times of bariatric surgery to assess the presence of NASH in patients with obesity, in the circuit of bariatric surgery. METHODS: We performed a retrospective study of 49 patients presenting high-grade obesity in the circuit of bariatric surgery, with liver biopsy. The patients underwent bariatric surgery at a single center in France and were followed for 2 years. The liver biopsies were performed intraoperatively on all 49 patients before the bariatric surgery. The primary endpoint of the study was to evaluate the relationships between steatohepatitis/liver fibrosis and the presence of diabetes and to evaluate the current relationships between the biochemical work-ups. Special importance was accorded to the correlations between vitamin D levels and the presence of hepatic steatosis, due to the antifibrogenic pattern in the liver, as shown in many important papers in the field. RESULTS: Significant correlations were found between the presence of liver fibrosis and the presence of diabetes (p = 0.022), but not regarding the antidiabetic treatment. An important correlation was found between the vitamin D levels and the presence of liver fibrosis, as well as with the levels of A1C hemoglobin and LDL cholesterol levels. CONCLUSIONS: Vitamin D deficiency presents a strong correlation with hepatic steatosis in individuals with morbid obesity. Correcting vitamin D deficiency may present a beneficial role in treating hepatic steatosis, diabetes, and cardiovascular risk in patients with morbid obesity.

Effects of Anthocyanins on Vascular Health.

Cardiovascular disorders are leading mortality causes worldwide, often with a latent evolution. Vascular health depends on endothelial function, arterial stiffness, and the presence of atherosclerotic plaques. Preventive medicine deserves special attention, focusing on modifiable cardiovascular risk factors, including diet. A diet rich in fruits and vegetables has well-known health benefits, especially due to its polyphenolic components. Anthocyanins, water-soluble flavonoid species, responsible for the red-blue color in plants and commonly found in berries, exert favorable effects on the endothelial function, oxidative stress, inhibit COX-1, and COX-2 enzymes, exert antiatherogenic, antihypertensive, antiglycation, antithrombotic, and anti-inflammatory activity, ameliorate dyslipidemia and arterial stiffness. The present review aims to give a current overview of the mechanisms involved in the vascular protective effect of anthocyanins from the human diet, considering epidemiological data, in vitro and in vivo preclinical research, clinical observational, retrospective, intervention and randomized studies, dietary and biomarker studies, and discussing preventive benefits of anthocyanins and future research directions.

Plasma ghrelin, adiponectin and leptin levels in obese rats with type 2 diabetes mellitus after sleeve gastrectomy and gastric plication.

The prevalence of obesity has increased in recent decades and has become a public health problem. In obesity patients the metabolism of almost all adipokines is markedly dysregulated. Studies regarding levels of ghrelin, leptin, and adiponectin after bariatric surgery reveal contradictory results. The purpose of the present study was to analyze modification of body weight and plasma levels of fasting glucose, ghrelin, adiponectin and leptin, in obese rats with T2DM after sleeve gastrectomy (SG), gastric plication (GP) and sham-operated (SO). Eighteen specimens where randomized to three weight-matched groups: Group SG underwent sleeve gastrectomy (n=6), group GP underwent gastric plication (n=6) and the control group SO underwent sham surgery (n=6). Upon surgery a normal rat chow diet (Bio-Serv® product no. F4031) was fed to the rats until the end of the experiment. Additional blood samples were harvested after 4 weeks. The results revealed that body mass decreased in the SG (783.17±101.39 vs. 658.33±86.57 g; P<0.0001) and the GP (781.33±103.12 vs. 702.33±84.06 g; P=0.004) rats after surgery. There were significant lower fasting glucose levels at 4 weeks postoperative in the SG group compared to the SO group (83.1±12.81 vs. 104.5±9.81 mg/dl; P=0.016). The same trend was observed in the GP group vs. the SO group (86.7±11.43 vs. 104.5±9.81 mg/dl; P=0.026). There was no difference regarding mean glucose levels between the SG group compared to the GP group (P>0.05). Plasma acylated ghrelin and leptin levels decreased four weeks after surgery compared to preoperative levels, while adiponectin levels increased four weeks after surgery in the SG and GP groups, respectively. The present study revealed that plasma glucose levels, ghrelin and leptin levels decreased after SG and GP, while adiponectin levels improved. This suggests that there may be hormonal contribution in weight loss.

Shear Wave Elastography in Patients with Primary and Secondary Hyperparathyroidism.

OBJECTIVES: In this study, we aim to determine the elastographic characteristics of both primary and secondary hyperparathyroidism using shear wave elastography. We also aim to evaluate the elastographic differences between them, as well as the differences between the parathyroid, thyroid, and muscle tissue, in order to better identify a cutoff value for the parathyroid tissue. METHODS: In this prospective study, we examined a total of 68 patients with hyperparathyroidism, divided into two groups; one group consisted of 27 patients with primary hyperparathyroidism and the other group consisted of 41 selected patients with confirmed secondary hyperparathyroidism. The elasticity index (EI) was determined in the parathyroid, thyroid, and muscle tissue. The determined values were compared to better identify the parathyroid tissue. RESULTS: The median value of mean SWE values measured for parathyroid adenomas from primary hyperparathyroidism was 4.86 kPa. For secondary hyperparathyroidism, the median value of mean SWE was 6.96 KPa. The median (range) presurgical values for parathormone (PTH) and calcium were 762.80 pg/mL (190, 1243) and 9.40 mg/dL (8.825, 10.20), respectively. We identified significant elastographic differences between the two groups (p < 0.001), which remained significant after adjusting elastographic measures to the nonparametric parameters, such as the parathormone value and vitamin D (p < 0.001). The cutoff values found for parathyroid adenoma were 5.96 kPa and for parathyroid tissue 9.58 kPa. CONCLUSIONS: Shear wave elastography is a helpful tool for identifying the parathyroid tissue, in both cases of primary and secondary hyperparathyroidism, as there are significant differences between the parathyroid, thyroid, and muscle tissue. We found a global cutoff value for the parathyroid tissue of 9.58 kPa, but we must keep in mind that there are significant elastographic differences between cutoffs for primary and secondary hyperparathyroidism.

Lemon Balm Extracts Prevent Breast Cancer Progression In Vitro and In Ovo on Chorioallantoic Membrane Assay.

Breast cancer is the most frequently diagnosed malignant pathology, representing the primary cause of cancer death in women. Natural products are an appealing strategy to limit the progression of the disease. Targeting angiogenesis in breast cancer may positively impact on poor prognosis of breast cancer. As source of natural compounds, we investigated the leaves of Melissa officinalis L. (MO), known as lemon balm, an aromatic plant that spontaneously grows in the South and Western areas of Romania, being traditionally recommended as anxiolytic, antispasmodic, or as digestive remedy. Our aim was to investigate the phytochemical profiling and the antiangiogenic and chemopreventive bioactivity of MO from Banat region, on breast cancer. Two ethanolic extracts of MO (MOE96 and MOE70) and one methanolic extract (MOM80) were subjected to polyphenol and triterpene profiling by HPLC-MS, and the antioxidant capacity was evaluated. The antiangiogenic potential was investigated using the chorioallantoic membrane assay (CAM). The MTT(3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide) assay was used to investigate the cytotoxic effects on MCF-7 and MDA-MB-231breast cancer cells, as well as on MCF-10A normal breast epithelial cells, while apoptosis was performed by DAPI staining. Rosmarinic acid (RA) and ursolic acid (UA) were revealed as dominant phytocompounds. The highest concentration in phytochemicals were found in MOM80; MOE96 was more concentrated in UA, while MOE70 extracted more RA. MOE96 inhibited cancer progression and angiogenesis in the in ovo CAM model using MDA-MB-231 cells, inhibiting breast cancer progression and angiogenesis for the MDA-MB-231 breast cancer cell line; no secondary tumoral areas were registered, indicative for a preventive effect against breast tumor cell invasiveness. The highest cell inhibitory activity was also exhibited by MOE96, in particular against the estrogen receptor positive MCF7 breast cancer cell line, with no cytotoxic effect on healthy cells. The estrogen receptor positive MCF7 cell line proved to be more sensitive to the extract antiproliferative activity than the triple negative MDA-MB-231 breast cancer cell line. Nevertheless, the chemopreventive potential of MOE96 extract is phenotype-dependent and is rather related to the apoptosis and antiangiogenic effects suggesting a multitargeted mechanism of action due to its multiple compound composition next to a concentration ratio of RA : UA in favor of UA.

Thyroid Pathology in End-Stage Renal Disease Patients on Hemodialysis.

OBJECTIVES: Chronic kidney disease is a rising cause of morbidity and mortality in developed countries, including end-stage renal disease (ESRD). The prevalence of thyroid comorbidities in persons with chronic kidney disease is documented higher than in normal population. The study aims to investigate the prevalence of morphological and functional thyroid disorders in patients with chronic kidney disease, with renal replacement therapy (hemodialysis). METHODS: A cross-sectional study was performed on 123 consecutive patients with chronic kidney disease stage 5, on hemodialysis during a period of one month (May 2019-June 2020). All patients were enrolled for maintenance hemodialysis in B Braun Hemodialysis Center Timisoara and were examined on conventional 2B ultrasound. Thyroid blood tests were done, including serum free thyroxin (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) at the time of starting hemodialysis. RESULTS: We evaluated 123 patients (male to female ratio 70/53) mean age 62.2 ± 11.01, mostly above 65 years old, enrolled in the end-stage renal disease program, on renal replacement therapy. From the cohort, 76/123 presented thyroid disease, including autoimmune hypothyroidism, nodular goiter or thyroid cancer. Among them, 63 patients presented nodular goiter, including 3 thyroid cancers, confirmed by surgery and histopathological result, 22 patients had thyroid autoimmune disease. The serum thyroid-stimulating hormone levels found in the cohort was 3.36 ± 2.313 mUI/mL, which was in the normal laboratory reference range. The thyroid volume was 13 ± 7.18 mL. A single patient in the cohort presented Graves Basedow disease, under treatment and three patients present subclinical hyperthyroidism. We have found that thyroid disease risk is increased by 3.4-fold for the female gender and also the increase of body mass index (BMI) with one unit raises the risk of developing thyroid disease with 1.083 times (p = 0.018). CONCLUSION: To conclude, this study aimed to quantify the prevalence of thyroid disease in end-stage kidney disease population, especially nodular goiter, important for differential diagnosis in cases with secondary hyperparathyroidism. Thyroid autoimmune disease can be prevalent among these patients, as symptoms can overlap those of chronic disease and decrease the quality of life. We have found that thyroid disease has a high prevalence among patients with end-stage renal disease on hemodialysis. Thyroid goiter and nodules in ESRD patients were more prevalent than in the general population. Clinical surveillance and routine screening for thyroid disorders can improve the quality of life in these patients.

TI-RADS Diagnostic Performance: Which Algorithm is Superior and How Elastography and 4D Vascularity Improve the Malignancy Risk Assessment.

Given the increased prevalence of thyroid nodules in the general population (~50%), the real challenge resides in correctly recognizing the suspicious ones. This study proposes to compare four important Thyroid Imaging and Reporting Data Systems (TI-RADS) and evaluate the contribution of elastography and 4D Color Doppler assessment of vascularity in estimating the risk of malignancy. In the study, 133 nodules with histopathological examination were included. Of these, 35 (26.31%) proved to be malignant. All nodules were classified using the four selected systems and our proposed improved score. The American College of Radiology (ACR) and EU TI-RADS had good sensitivity (94.28%, 97.14%) and NPV (93.33%, 95.83%), but fairly poor specificity (31.81%, 23.46%) and PPV (35.48%, 31.19%), with an accuracy of 42.8% and 45.8%, respectively. Horvath TI-RADS had better accuracy of 66.9% and somewhat improved specificity (62.24%), but poorer sensitivity (80%). Russ' French TI-RADS includes elastography in the risk assessment strategy. This classification proved superior in all aspects (Se: 91.42%, Sp:82.65%, NPV:96.42%, PPV:65.30%, and Acc of 84.96%). The mean strain ratio (SR) value for malignant lesions was 5.56, while the mean SR value for benign ones was significantly lower, 2.54 (p < 0.05). It also correlated well with the response variable: histopathological result (p < 0.001). Although, adding 4D vascularity to the French score generated a similar calculated accuracy and from a statistical point of view, the parameter itself proved beneficial for predicting the malignancy risk (p < 0.001) and may add important knowledge in uncertain situations. Advanced ultrasound techniques definitely improved the risk estimation and should be used more extensively.

Shear Wave Elastography versus Strain Elastography in Diagnosing Parathyroid Adenomas.

OBJECTIVES: The aim of the study was to compare elastographic means in parathyroid adenomas, using shear wave elastography and strain elastography. METHODS: This prospective study examined 20 consecutive patients diagnosed with primary hyperparathyroidism and parathyroid adenoma, confirmed by biochemical assay, technetium-99 sestamibi scintigraphy, and pathology report, after parathyroid surgery. All patients were examined on conventional 2B ultrasound, 2D shear wave elastography, and strain elastography. We determined using 2D shear wave elastography (SWE) the elasticity index (EI) in parathyroid adenoma, thyroid parenchyma, and surrounding muscle and examined using strain elastography the parathyroid adenoma, and determined the strain ratio with the thyroid tissue and muscle tissue. RESULTS: All patients had positive sestamibi scintigraphy and underwent surgery, with confirmation of parathyroid adenoma in all cases. The mean parathormone (PTH) value before surgery was 153.29 pg/ml (36.5, 464.8) and serum calcium concentration was 10.5 mg/dl (9, 11.5). We compared using 2D-SWE and strain elastography parathyroid adenoma with thyroid tissue and with surrounding muscle. The mean EI measured by SWE in parathyroid adenoma was 4.74 ± 2.74 kPa and in thyroid parenchyma was 11.718 ± 4.206 kPa (mean difference = 6.978 kPa, p < 0.001), and the mean EI value in muscle tissue was 16.362 ± 3.829 kPa (mean difference = 11.622, p < 0.001). Using ROC analysis, we found that an EI below 7 kPa correctly identifies parathyroid tissue. We evaluated parathyroid adenomas using strain elastography by color mapping and strain ratio as a semiquantitative measurement; however, we could not find any statistical correlation comparing the strain ratio obtained from the parathyroid adenoma with the thyroid tissue (p=0.485). CONCLUSION: Ultrasound elastography is a helpful tool in identifying parathyroid adenomas. A cutoff value below 7 kPa can be used in 2D-SWE. Color maps in strain elastography without adding strain ratio can be used, parathyroid adenoma being identified as score 1 in the Rago criteria.

Advanced Ultrasound Application - Impact on Presurgical Risk Stratification of the Thyroid Nodules.

AIM: Current major guidelines recommend risk stratification of the thyroid nodules, after each diagnostic evaluation, in order to focus attention on potentially risky nodules. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in this process, compared with conventional stratification models, in order to reduce unnecessary fine-needle biopsies, respectively, surgery. MATERIAL AND METHODS: We evaluated 261 cases (261 nodules) using conventional ultrasound (2B), real-time Doppler evaluation (4D) respectively, real-time elastography, using a linear multifrequency probe and a linear volumetric probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All the nodules were classified using a risk stratification model comprising seven conventional US characteristics, two 4 D characteristics and a color map RTE aspect. The results were compared with the pathology results, considered the golden standard diagnosis. RESULTS: The prevalence of malignant nodules was 21.83% (57 cases). Conventional risk classification generated: 106 low-risk cases, 113 intermediate-risk and 42 high-risk cases. Our proposed risk classification changes the conventional risk classification with a risk upgrade in 27 cases and with a risk downgrade in 69 cases. The diagnostic quality of the combined risk stratification model was better, considering a low-risk category predictive for benignancy and a high category predictive for malignancy: Sensitivity: 80.88% versus 49.01%, respectively, Specificity: 91.22% versus 54.38. The diagnostic power differences were observed regardless of the nodule size. CONCLUSION: Advanced ultrasound techniques did add diagnostic value in the presurgical risk assessment of the thyroid nodules.

Shear Wave Elastography in Diagnosing Secondary Hyperparathyroidism.

This study evaluates the diagnostic value of two-dimensional shear wave elastography (2 D-SWE) technique in the evaluation of hyperplastic parathyroid glands in cases with secondary and tertiary hyperparathyroidism. A total of 59 patients (end-stage renal disease, under supplemental dialysis program) with visible parathyroid hyperplastic glands on ultrasound, confirmed by biochemical assay and scintigraphy, were enrolled; they were examined on grayscale ultrasound and 2 D shear wave elastography. We determined the elasticity index (EI) in the parathyroid gland, thyroid parenchyma and surrounding muscles, and the elasticity ratio of hyperplastic parathyroid glands compared to muscle, specifically sternocleidomastoid muscle. Patients presented fibrocystic bone disease with secondary hyperparathyroidism induced by end-stage chronic kidney disease; being on prolonged chronic dialysis therapy, they had positive sestamibi scintigraphy and high values of serum parathormone (1141.04 pg/mL). Nodules placed posterior to the thyroid capsule that were cystic, had a hypoechoic aspect, and were homogenous with an independent afferent artery were found. Mean EI in the parathyroid gland was 7.83 kPa, the median value in thyroid parenchyma was 13.76 kPa, and mean muscle EI value was 15.78 kPa. The observed mean parathyroid/muscle SWE ratio was 0.5356 and the value for parathyroid/normal thyroid parenchyma was 0.5995. Using receiver operating characteristic (ROC) analysis, we found that EI below 9.74 kPa correctly identifies parathyroid tissue, with a sensitivity of 94.8%, specificity of 90.7%, and accuracy of 92.26% when compared to normal thyroid tissue. Compared with the muscle tissue, we identified that EI below 9.98 kPa has a sensitivity, specificity, and accuracy of 93.8%, 90.7%, and 91.75%, respectively. Ultrasound elastography is a helpful tool in identifying parathyroid hyperplasia in patients with chronic kidney disease. A cutoff value of 9.98 kPa can be used in 2 D-SWE for accurate diagnosis of parathyroid disease.

Strain Elastography as a Valuable Diagnosis Tool in Intermediate Cytology (Bethesda III) Thyroid Nodules.

Fine needle aspiration (FNA) is considered the gold standard in the diagnostic of thyroid nodules. Using the recommended BETHESDA reporting system, up to 20% of results are classified as intermediate cytology. As there is no consensus whether ultrasound evaluation, lobectomy or surgery is the best treatment option, intermediate cytology results are considered a grey zone of the FNA. The main aim of our study was to evaluate the performance of combined advanced ultrasound techniques in the process of diagnosis and evaluation of the intermediate cytology cases after FNA. We evaluated 54 consecutive cases with intermediate cytology on FNA, using conventional B-mode ultrasound (2B), and strain elastography, using a linear multifrequency 6-13 MHz linear probe (Hitachi Prerius Machine, Hitachi Inc, Japan). All nodules were classified with our Thyroid Imaging Report and Data System (TI-RADS) proposed model, considering: vertical appearance, with antero-posterior diameter bigger than the transvers diameter, the so called taller than wide shape, irregular borders, intranodular inhomogeneity, marked hypoecogenicity, micro calcifications, the presence of suspect lymph nodes, and increased stiffness as suspicious for malignancy. The classification outcomes were compared with the pathology results, considered the gold standard diagnosis. The prevalence of cancer was 28.8%, with 13/45 cases having a clear diagnostic of cancer. Six cases were diagnosed with borderline follicular neoplasia, a category with unclear evolution, also considered as malignant in the analysis of the imaging results. In total, 16/19 cancer cases had increased stiffness on elastography. The cancer prevalence increased with TI-RADS category, being 25% in TI-RADS 4b category and 92.8% in TI-RADS 5 category. The AUROC (Area Under Receiver Operating Curve) of elastography alone, in differentiation of malignant thyroid nodules was 74.9%; the combination of elastographic and conventional ultrasound characteristics generated an even better AUROC, of 84.5%. The combined conventional ultrasound and elastography identified thyroid cancer in cases with intermediate cytology with a sensitivity of 89.5% with a specificity of 50%. High risk thyroid nodules, identified by combined high risk conventional ultrasound characteristics and increased stiffness, on strain elastography, are highly predictive for malignancy, in the intermediate cytology cases.

Ethinylestradiol and Levonorgestrel as Active Agents in Normal Skin, and Pathological Conditions Induced by UVB Exposure: In Vitro and In Ovo Assessments.

The link between melanoma development and the use of oral combined contraceptives is not fully elucidated, and the data concerning this issue are scarce and controversial. In the present study, we show that the components of oral contraceptives, ethinylestradiol (EE), levonorgestrel (LNG), and their combination (EE + LNG) ± UVB (ultraviolet B radiation) induced differential effects on healthy (human keratinocytes, fibroblasts, and primary epidermal melanocytes, and murine epidermis cells) and melanoma cells (human-A375 and murine-B164A5), as follows: (i) at low doses (1 µM), the hormones were devoid of significant toxicity on healthy cells, but in melanoma cells, they triggered cell death via apoptosis; (ii) higher doses (10 µM) were associated with cytotoxicity in all cells, the most affected being the melanoma cells; (iii) UVB irradiation proved to be toxic for all types of cells; (iv) UVB irradiation + hormonal stimulation led to a synergistic cytotoxicity in the case of human melanoma cells-A375 and improved viability rates of healthy and B164A5 cells. A weak irritant potential exerted by EE and EE + LNG (10 µM) was assessed by the means of a chick chorioallantoic membrane assay. Further studies are required to elucidate the hormones' cell type-dependent antimelanoma effect and the role played by melanin in this context.

Inflammatory Markers for Arterial Stiffness in Cardiovascular Diseases.

Arterial stiffness predicts an increased risk of cardiovascular events. Inflammation plays a major role in large arteries stiffening, related to atherosclerosis, arteriosclerosis, endothelial dysfunction, smooth muscle cell migration, vascular calcification, increased activity of metalloproteinases, extracellular matrix degradation, oxidative stress, elastolysis, and degradation of collagen. The present paper reviews main mechanisms explaining the crosstalk between inflammation and arterial stiffness and the most common inflammatory markers associated with increased arterial stiffness, considering the most recent clinical and experimental studies. Diverse studies revealed significant correlations between the severity of arterial stiffness and inflammatory markers, such as white blood cell count, neutrophil/lymphocyte ratio, adhesion molecules, fibrinogen, C-reactive protein, cytokines, microRNAs, and cyclooxygenase-2, in patients with a broad variety of diseases, such as metabolic syndrome, diabetes, coronary heart disease, peripheral arterial disease, malignant and rheumatic disorders, polycystic kidney disease, renal transplant, familial Mediterranean fever, and oral infections, and in women with preeclampsia or after menopause. There is strong evidence that inflammation plays an important and, at least, partly reversible role in the development of arterial stiffness, and inflammatory markers may be useful additional tools in the assessment of the cardiovascular risk in clinical practice. Combined assessment of arterial stiffness and inflammatory markers may improve non-invasive assessment of cardiovascular risk, enabling selection of high-risk patients for prophylactic treatment or more regular medical examination. Development of future destiffening therapies may target pro-inflammatory mechanisms.

Gender Differences of Arterial Stiffness and Arterial Age in Smokers.

The present study aimed to find gender differences for arterial stiffness and arterial aging in smokers. A total of 147 smokers (71 male and 76 female, matched for age) were explored using an Arteriograph in a cross-sectional survey. Pulse wave velocity (PWV), arterial age (AA), brachial and aortic augmentation index (AixBrach, AixAo), and blood pressure variables were assessed. Data about smoking intensity, such as the number of cigarettes smoked daily, smoking period, and smoking pack years (SPY) were used. No significant differences were found for PWV, AA, AixBrach and AixAo. Significant correlations were found between SPY and PWV, augmentation indices, and AA, respectively. The cut-off values for SPY were higher for an increased arterial stiffness in male compared to female smokers (18.5 and 7.5 pack year, respectively). SPY is significantly associated with an increased arterial stiffness in smokers regardless of gender, and with an increased SBPAo only in female smokers. The results of our study indicate gender differences for arterial stiffness and arterial age in smokers.