Thyroid ultrasonography reporting: consensus of Italian Thyroid Association (AIT), Italian Society of Endocrinology (SIE), Italian Society of Ultrasonography in Medicine and Biology (SIUMB) and Ultrasound Chapter of Italian Society of Medical Radiology (SIRM)

Thyroid ultrasonography (US) is the gold standard for thyroid imaging and its widespread use is due to an optimal spatial resolution for superficial anatomic structures, a low cost and the lack of health risks. Thyroid US is a pivotal tool for the diagnosis and follow-up of autoimmune thyroid diseases, for assessing nodule size and echostructure and defining the risk of malignancy in thyroid nodules. The main limitation of US is the poor reproducibility, due to the variable experience of the operators and the different performance and settings of the equipments. Aim of this consensus statement is to standardize the report of thyroid US through the definition of common minimum requirements and a correct terminology. US patterns of autoimmune thyroid diseases are defined. US signs of malignancy in thyroid nodules are classified and scored in each nodule. We also propose a simplified nodule risk stratification, based on the predictive value of each US sign, classified and scored according to the strength of association with malignancy, but also to the estimated reproducibility among different operators

Vitamin D deficiency: A new risk factor for type 2 diabetes?

Recent compelling evidence suggests a role of vitamin D deficiency in the pathogenesis of insulin resistance and insulin secretion derangements, with a consequent possible interference with type 2 diabetes mellitus. The mechanism of this link is incompletely understood. In fact, vitamin D deficiency is usually detected in obesity in which insulin resistance is also a common finding. The coexistence of insulin resistance and vitamin D deficiency has generated several hypotheses. Some cross-sectional and prospective studies have suggested that vitamin D deficiency may play a role in worsening insulin resistance; others have identified obesity as a risk factor predisposing individuals to exhibit both vitamin D deficiency and insulin resistance. The available data from intervention studies are largely confounded, and inadequate considerations of seasonal effects on 25(OH)D concentrations are also a common design flaw in many studies. On the contrary, there is strong evidence that obesity might cause both vitamin D deficiency and insulin resistance, leaving open the possibility that vitamin D and diabetes are not related at all. Although it might seem premature to draw firm conclusions on the role of vitamin D supplementation in reducing insulin resistance and preventing type 2 diabetes, this manuscript will review the circumstances leading to vitamin D deficiency and how such a deficiency can eventually independently affect insulin sensitivity. © 2012 S. Karger AG, Basel

25-hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25-hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin-sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin-sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin-sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low-density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin-sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = -0.58; P = 0.01), PTH (r = -0.44; P 0.01), insulin-sensitivity (r = -0.43; P < 0.01), total (r = -0.34; P = 0.030) and LDL (r = -0.40; P = 0.023) (but not high-density lipoprotein (HDL)) cholesterol, and triglycerides (r = -0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin-sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = -0.52; P < 0.01), whereas insulin-sensitivity was not significant. Our study suggested that there is no cause-effect relationship between vitamin D and insulin-sensitivity. In obesity, both low 25(OH)D concentration and insulin-resistance appear to be dependent on the increased body size. © 2010 The Obesity Society

PARP inhibitors affect growth, survival and radiation susceptibility of human alveolar and embryonal rhabdomyosarcoma cell lines

PARP inhibitors (PARPi) are used in a wide range of human solid tumours but a limited evidence is reported in rhabdomyosarcoma (RMS), the most frequent childhood soft-tissue sarcoma. The cellular and molecular effects of Olaparib, a specific PARP1/2 inhibitor, and AZD2461, a newly synthesized PARP1/2/3 inhibitor, were assessed in alveolar and embryonal RMS cells both as single-agent and in combination with ionizing radiation (IR)

High-normal TSH values in obesity: is it insulin resistance or adipose tissue's guilt?

Objective: Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross-sectionally investigated the influence of metabolic features on hypothalamic-pituitary-thyroid axis in obesity. Design and methods: We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity-glucose uptake: r = -0.40; P = 0.04). Results: After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (β = 3.05; P = 0.01), whereas glucose uptake, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high-normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30-35 kg/m(2). This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg · kg(-1) · min(-1), respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m(2) vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se. Conclusion: Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance

Sotagliflozin, the first dual SGLT inhibitor. Current outlook and perspectives

Sotagliflozin is a dual sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor for the treatment of both type 1 (T1D) and type 2 diabetes (T2D). Sotagliflozin inhibits renal sodium-glucose co-transporter 2 (determining significant excretion of glucose in the urine, in the same way as other, already available SGLT-2 selective inhibitors) and intestinal SGLT-1, delaying glucose absorption and therefore reducing post prandial glucose. Well-designed clinical trials, have shown that sotagliflozin (as monotherapy or add-on therapy to other anti-hyperglycemic agents) improves glycated hemoglobin in adults with T2D, with beneficial effects on bodyweight and blood pressure. Similar results have been obtained in adults with T1D treated with either continuous subcutaneous insulin infusion or multiple daily insulin injections, even after insulin optimization. A still ongoing phase 3 study is currently evaluating the effect of sotagliflozin on cardiovascular outcomes (ClinicalTrials.gov NCT03315143). In this review we illustrate the advantages and disadvantages of dual SGLT 2/1 inhibition, in order to better characterize and investigate its mechanisms of action and potentialities

Smoke Evacuation During Laparoscopic Surgery: A Problem Beyond the COVID-19 Period. A Quantitative Analysis of CO2 Environmental Dispersion Using Different Devices

Background. The COVID-19 pandemic leads to several debates regarding the possible risk for healthcare professionals during surgery. SAGES and EAES raised the issue of the transmission of infection through the surgical smoke during laparoscopy. They recommended the use of smoke evacuation devices (SEDs) with CO2 filtering systems. The aim of the present study is to compare the efficacy of different SEDs evaluating the CO2 environmental dispersion in the operating theater. Methods. We prospectively evaluated the data of 4 group of patients on which we used different SEDs or standard trocars: AIRSEAL system (S1 group), a homemade device (S2 group), an AIRSEAL system + homemade device (S3 group), and with standard trocars and without SED (S4 group). Quantitative analysis of CO2 environmental dispersion was carried out associated to the following data in order to evaluate the pneumoperitoneum variations: a preset insufflation pressure, real intraoperative pneumoperitoneum pressure, operative time, total volume of insufflated CO2, and flow rate index. Results. 16 patients were prospectively enrolled. The [CO2] mean value was 711 ppm, 641 ppm, 593 ppm, and 761 ppm in S1, S2, S3, and S4 groups, respectively. The comparison between data of all groups showed statistically significant differences in the measured ambient CO2 concentration. Conclusion. All tested SEDs seem to be useful to reduce the CO2 environmental dispersion respect to the use of standard trocars. The association of AIRSEAL system and a homemade device seems to be the best solution combining an adequate smoke evacuation and a stable pneumoperitoneum during laparoscopic surgery

Analysis of adenomatous polyposis coli gene in thyroid tumours.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma

Insulin resistance alters islet morphology in nondiabetic humans

Type 2 diabetes is characterized by poor glucose uptake in metabolic tissues and manifests when insulin secretion fails to cope with worsening insulin resistance. In addition to its effects on skeletal muscle, liver, and adipose tissue metabolism, it is evident that insulin resistance also affects pancreatic β-Cells. To directly examine the alterations that occur in islet morphology as part of an adaptive mechanism to insulin resistance, we evaluated pancreas samples obtained during pancreatoduodenectomy from nondiabetic subjects who were insulin-resistant or insulin-sensitive. We also compared insulin sensitivity, insulin secretion, and incretin levels between the two groups. We report an increased islet size and an elevated number of band a-cells that resulted in an altered β-Cell-to-a-cell area in the insulin- resistant group. Our data in this series of studies suggest that neogenesis from duct cells and transdifferentiation of a-cells are potential contributors to the β-Cell compensatory response to insulin resistance in the absence of overt diabetes. © 2014 by the American Diabetes Association.