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Purpose: Dyslipidemia plays a pivotal role in increasing cardiovascular risk. In clinical practice the misleading association between altered lipid profile and obesity is common, therefore genetically inherited dyslipidemias may not completely be addressed among patients with overweight. Thus, we aim to investigate the influence of overweight and obesity on the lipid phenotype in a cohort of patients with different forms of dyslipidemia. Methods: A retrospective analysis was conducted on patients with dyslipidemia from 2015 to 2022. Patients were stratified in familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), non-familial hyperlipidemia or polygenic hypercholesterolemia (PH). Clinical characteristics and lipid profile were evaluated. Results: Of the total of 798 patients, 361 were affected by non-familial hyperlipidemia (45.2%), while FCHL, FH and PH was described in 19.9%, 14.0% and 20.9% of patients, respectively. Overweight prevalence was higher in FCHL and non-familial hyperlipidemia patients than FH and PH patients. Subjects with overweight and obesity were independently associated with lower levels of high-density lipoprotein cholesterol (HDL-C) compared to patients with normal weight (52.4 and 46.0 vs 58.1, respectively; p< 0.0001); levels of triglycerides (TG) and non-HDL-C were higher in patients with overweight and obesity than patients with normal weight (257.3 and 290.9 vs 194.8, and 221.5 and 219.6 vs 210.1, p< 0.0001 and p= 0.01, respectively), while no differences were observed between patients with overweight and obesity. Conclusion: While dyslipidemias can be influenced by various factors, an important determinant may lie in genetics, frequently acting as an underlying cause of altered lipid profiles, even in cases of overweight conditions.

Purpose: Primary hyperparathyroidism (PHPT) is associated with long-term implications on many aspects of general health and has been linked to various tumor types. This retrospective monocentric study aimed to evaluate the prevalence of primary hyperparathyroidism in a cohort of thyroid cancer patients and its impact on their general prognosis. Methods: The prevalence of primary hyperparathyroidism (concomitant or subsequent) was retrospectively evaluated in a cohort of 450 patients with a diagnosis of differentiated thyroid cancer. Its association with oncological outcomes and overall survival was analysed. Results: Among the study population, 30 patients (6,7%) were diagnosed with primary hyperparathyroidism. This subgroup displayed older age at diagnosis and a higher prevalence of prior cardiovascular disease, other primary tumors and multinodular goiter (p < 0.001). PHPT was associated with increased mortality; however, no significant difference in thyroid cancer-specific mortality was found. Conclusion: A significant proportion of thyroid cancer patients may present concomitant primary hyperparathyroidism, which appears to negatively affect long-term prognosis, independently from their oncological outcomes.

Purpose: Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC. Methods: In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography. Results: An impaired thyroid function was recorded in 23.4% of patients (n= 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p= 0.021) and multivariate analyses (p= 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p= 0.031). Conclusions: Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.

Background: The incidence of neuroendocrine neoplasm (NEN) and related carcinoid syndrome (CaS) has increased markedly in recent decades, and women appear to be more at risk than men. As per other tumors, gender may be relevant in influencing the clinical and prognostic characteristics of NEN-associated CS. However, specific data on carcinoid syndrome (CaS) are still lacking. Purpose: To evaluate gender differences in clinical presentation and outcome of CaS. Methods: Retrospective analysis of 144 CaS patients from 20 Italian high-volume centers was conducted. Clinical presentation, tumor characteristics, therapies, and outcomes (progression-free survival, PFS, overall survival, OS) were correlated to gender. Results: Ninety (62.5%) CaS patients were male. There was no gender difference in the site of primary tumor, tumor grade and clinical stage, as well as in treatments. Men were more frequently smokers (37.2%) and alcohol drinkers (17.8%) than women (9.5%, p= 0.002, and 3.7%, p= 0.004, respectively). Concerning clinical presentation, women showed higher median number of symptoms (p= 0.0007), more frequent abdominal pain, tachycardia, and psychiatric disorders than men (53.3% vs 70.4%, p= 0.044; 6.7% vs 31.5%, p= 0.001; 50.9% vs. 26.7%, p= 0.003, respectively). Lymph node metastases at diagnosis were more frequent in men than in women (80% vs 64.8%; p= 0.04), but no differences in terms of PFS (p= 0.51) and OS (p= 0.64) were found between gender. Conclusions: In this Italian cohort, CaS was slightly more frequent in males than females. Gender-related differences emerged in the clinical presentation of CaS, as well as gender-specific risk factors for CaS development. A gender-driven clinical management of these patients should be advisable.

Purpose: In the last edition of the American Joint Committee on Cancer (AJCC) staging system, differentiated thyroid cancers (DTC) showing microscopic extrathyroidal extension (mETE) are considered comparable to intrathyroidal cancers for their clinical behavior and prognosis. The aim of the study is to evaluate the impact of this updated assessment of T, when applied to the postoperative recurrence risk stratification, according to the American Thyroid Association Guidelines (ATA-RR). Methods: One-hundred DTC patients who underwent total thyroidectomy were retrospectively evaluated. The downstaging of mETE was introduced in the definition of T, and the updated classification defined as modified ATA-RR (ATAm-RR). For each patient, post-surgical basal and stimulated thyroglobulin (Tg) levels, neck ultrasound (US) and post-ablative 131-I whole body scan (WBS) reports were considered. The predictive performance (PP) of disease recurrence was calculated both for each single parameter, as well as for all of them. Results: According to ATAm-RR classification, 19/100 patients (19%) were downstaged. ATA-RR proved a significant PP for disease recurrence (DR) (sensitivity 75.0%, specificity 63.0%, p= 0.023). However, ATAm-RR performed slightly better due to an increased specificity (sensitivity 75.0%, specificity 83.7%, p< 0.001). For both classifications, the PP was optimal when all the above-mentioned predictive parameters were considered. Conclusion: Our results suggest that the new assessment of T considering mETE resulted in a downgrading of ATA-RR class in a significant number of patients. This provides a better PP for disease recurrence, and the best PP was obtained when considering the whole predictive variables together.

Purpose: Sodium is essential to life. However, its dietary excess is detrimental to the cardiovascular system, and sodium restriction is a crucial step in cardiovascular prevention. Iodine deficiency has been fought worldwide for decades, and substantial success has been achieved introducing the use of iodine-enriched salt. Nevertheless, areas of iodine deficiency persist around the world, both in developing and industrialized countries, and a major concern affecting dietary sodium reduction programs is represented by a possible iodine intake deficiency. There are substantial differences in the source of alimentary iodine among countries, such as iodized salt added, household tap water, seafood, or salt employed in packaged food. It is clear that a sodium-restricted diet can induce differences in terms of iodine intake, depending on the country considered. Moreover, iodine status has undergone relevant changes in many countries in the last years. Methods: Systematic review of literature evidence about the possible effects of sodium restriction on population iodine status. Results: To date, the available results are conflicting, depending on country, salt iodization policy, as well as time frame of data collection. However, to ensure an optimal iodine supply by salt fortification, without exceeding the current recommendation by World Health Organization for salt intake, seems to be an achievable goal. Conclusion: A balanced approach may be obtained by an adequate iodine concentration in fortified salt and by promoting the availability of iodized salt for household consumption and food industry use. In this scenario, updated prospective studies are strongly needed.

Octreotide and lanreotide, the first-generation somatostatin analogs, successfully control hormone hyperproduction, and related syndromes, in patients with acromegaly and neuroendocrine tumors. However, their anti-tumor effect, rather evident in large number of pituitary adenomas in acromegalic patients, has been hypothesized for a long time in patients with neuroendocrine tumors as well, although a significant tumor shrinkage has rarely been observed. However, the recent publication of the CLARINET study has strengthened the evidence, already emerged with the PROMID trial, that the long-term treatment with the first-generation long-acting somatostatin analogs may exert an anti-tumor activity on G1 and G2 enteropancreatic neuroendocrine tumors, as well. After the publication, majority of international guidelines have updated their algorithms in line with these results and this class of drugs obtained the indication as anti-tumor agents in the majority of patients with neuroendocrine tumors.

The shape optimisation involving complex flows, and based on direct CFD approaches, has now become very possible within industrial contexts, thanks to recent advances in optimal design technologies. However, one key remaining issue is related with the way the shape deformations are modelled. This paper presents the development of such an optimisation procedure, applied to a car engine air intake port, and compares two alternative methods for the shape deformation modelling. Global port variations are defined through a set of shape parameters. The first option consists in building a CAD model (Catia v5) to allow deformations, followed by a grid generation stage with tools enabling to generate and adapt the mesh to shape variations (Gridgen). The second option consists in starting from a grid done for a given shape, and defining parametric deformations on this grid, with a morphing tool (Sculptor). Then, after both modelling methods, the flow calculation is carried out with a CFD solver (Fluent). The resulting fields are processed by a flow post-processor (Fieldview) and by a Matlab procedure to extract the global criteria involved as optimisation objectives: the flow rate and the tumble. All this process is bundled within the modeFRONTIER multi-objective design environment. Similar optimisation approaches were led on both cases, involving mixed response surfaces – direct calculation evaluations of the designs, and a multi-objective genetic algorithm. The paper presents the main results, highlights the advantages and shortcomings of both modelling methods, and provides guidelines for their use and improvements, in view of practical industrial applications.

The shape optimisation involving complex flows, and based on direct CFD approaches, has now become very possible within industrial contexts, thanks to recent advances in optimal design technologies. However, one key remaining issue is related with the way the shape deformations are modelled. This paper presents the development of such an optimisation procedure, applied to a car engine air intake port, and compares two alternative methods for the shape deformation modelling. Global port variations are defined through a set of shape parameters. The first option consists in building a CAD model (Catia v5) to allow deformations, followed by a grid generation stage with tools enabling to generate and adapt the mesh to shape variations (Gridgen). The second option consists in starting from a grid done for a given shape, and defining parametric deformations on this grid, with a morphing tool (Sculptor). Then, after both modelling methods, the flow calculation is carried out with a CFD solver (Fluent). The resulting fields are processed by a flow post-processor (Fieldview) and by a Matlab procedure to extract the global criteria involved as optimisation objectives: the flow rate and the tumble. All this process is bundled within the modeFRONTIER multi-objective design environment. Similar optimisation approaches were led on both cases, involving mixed response surfaces ? direct calculation evaluations of the designs, and a multi-objective genetic algorithm. The paper presents the main results, highlights the advantages and shortcomings of both modelling methods, and provides guidelines for their use and improvements, in view of practical industrial applications.