Glycemic control and cancer outcomes in oncologic patients with diabetes: an Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical view.

BACKGROUND:  Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. PURPOSE:  The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.

Rachel score: a nomogram model for predicting the prognosis of lung neuroendocrine tumors.

BACKGROUND: Lung NET, classified in typical carcinoids (TC) and atypical carcinoids (AC), are highly heterogeneous in their biology and prognosis. The histological subtype and TNM stage are well-established prognostic factors for lung NET. In a previous work by our group, we demonstrated a significant impact of laterality on lung NET survival outcomes. MATERIALS AND METHODS: We developed a nomogram that integrates relevant prognostic factors to predict lung NET outcomes. By adding the scores for each of the variables included in the model, it was possible to obtain a prognostic score (Rachel score). Wilcoxon non-parametric statistical test was applied among parameters and Harrell's concordance index was used to measure the models' predictive power. To test the discriminatory power and the predictive accuracy of the model, we calculated Gonen and Heller concordance index. Time-dependent ROC curves and their area under the curve (AUC) were used to evaluate the models' predictive performance. RESULTS: By applying Rachel score, we were able to identify three prognostic groups (specifically, high, medium and low risk). These three groups were associate to well-defined ranges of points according to the obtained nomogram (I: 0-90, II: 91-130; III: > 130 points), providing a useful tool for prognostic stratification. The overall survival (OS) and progression free survival (PFS) Kaplan-Meier curves confirmed significant differences (p < 0.0001) among the three groups identified by Rachel score. CONCLUSIONS: A prognostic nomogram was developed, incorporating variables with significant impact on lung NET survival. The nomogram showed a satisfactory and stable ability to predict OS and PFS in this population, confirming the heterogeneity beyond the histopathological diagnosis of TC vs AC.

Role of thyroid stimulating hormone in the maintenance and functioning of the human corpus luteum.

PURPOSE: To evaluate the impact of high thyroid stimulating hormone (TSH) levels on human granulosa-luteal (hGL) cells. METHODS: hGL cells were isolated from follicular aspirates derived from patients undergoing IVF treatment without any thyroid disorder (serum TSH 0.5-2 mU/L). Cells were cultured at 37 °C in DMEM, supplemented with 5% FBS. The cells were treated with 1 nM LH and increasing concentrations of TSH. At the end of culture, conditioned medium and cells were collected to analyze progesterone production, cell viability, and mRNA levels of genes involved in the steroidogenesis process. Human ovarian tissues were analyzed for TSH receptor (TSHR) expression by IHC. RESULTS: The expression of TSHR was detected in human corpus luteum by IHC and in hGL by RT-PCR. In hGL cells, TSH treatment did not modulate progesterone production nor the expression of steroidogenic genes, such as p450scc and HSD3b 1/2. However, TSH induced a dose-dependent increase in cell death. Finally, TSH did not affect LH-induced p450scc and HSD3b1/2 expression while LH partially reverted TSH negative effect on cell death in hGL. CONCLUSIONS: Elevated TSH levels in hypothyroid women may be associated with impaired CL functioning and maintenance. These findings open a new line of research for the importance of the treatment of women with thyroid dysfunction that could contribute to the onset of infertility.

Gender-related differences in patients with carcinoid syndrome: new insights from an Italian multicenter cohort study.

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.

Diabetes management in cancer patients. An Italian Association of Medical Oncology, Italian Association of Medical Diabetologists, Italian Society of Diabetology, Italian Society of Endocrinology and Italian Society of Pharmacology multidisciplinary consensus position paper.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

MiRNA dysregulation underlying common pathways in type 2 diabetes and cancer development: an Italian Association of Medical Oncology (AIOM)/Italian Association of Medical Diabetologists (AMD)/Italian Society of Diabetology (SID)/Italian Society of Endocrinology (SIE)/Italian Society of Pharmacology (SIF) multidisciplinary critical view.

Increasing evidence suggests that patients with diabetes, particularly type 2 diabetes (T2D), are characterized by an increased risk of developing different types of cancer, so cancer could be proposed as a new T2D-related complication. On the other hand, cancer may also increase the risk of developing new-onset diabetes, mainly caused by anticancer therapies. Hyperinsulinemia, hyperglycemia, and chronic inflammation typical of T2D could represent possible mechanisms involved in cancer development in diabetic patients. MicroRNAs (miRNAs) are a subset of non-coding RNAs, ⁓22 nucleotides in length, which control the post-transcriptional regulation of gene expression through both translational repression and messenger RNA degradation. Of note, miRNAs have multiple target genes and alteration of their expression has been reported in multiple diseases, including T2D and cancer. Accordingly, specific miRNA-regulated pathways are involved in the pathogenesis of both conditions. In this review, a panel of experts from the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provide a critical view of the evidence about the involvement of miRNAs in the pathophysiology of both T2D and cancer, trying to identify the shared miRNA signature and pathways able to explain the strong correlation between the two conditions, as well as to envision new common pharmacological approaches.

[Atherosclerotic cardiovascular disease, lipemic disorders, hypertension, obesity and diabetes mellitus in the population of a metropolitan area of southeastern Brazil. II--Lipemic disorders]. / Doenças cardiovasculares ateroscleróticas, dislipidemias, hipertensão, obesidade e diabetes melito em população da área metropolitana da região Sudeste Do Brasil: II--dislipidemias.

This study has sought to characterize the prevalence of lipemic disorders and other risk factors of atheroschlerotic cardiovascular disease in population groups of Cotia county in Greater S. Paulo, Brazil. The population groups were defined on the basis of socio-economic characteristics and geographical location within the county such as provided elements for the delimitation of the "study areas". A sample representative of each of these areas was taken, constituting in all 1,041 individuals. The data related to eating habits were collected from a sub-sample of 568 people. The lipemic disorders diagnosed were as follows: high risk hypercholesterolemias with values approximately 240 mg/dl for total cholesterol and approximately 160 mg/dl for LDL-cholesterol; borderline risk hypercholesterolemias with values > 200 mg/dl and > 130 mg/dl for total cholesterol and LDL-cholesterol respectively; hypertriglyceridemia, with values approximately 250 mg/dl. The following risk factors were included: atherogenic eating habits (consumption of proteins of animal origin, saturated fats and cholesterol), smoking, drinking, sedentary life style, obesity (IMC > 25 kg/m2), hypertension (140/90 mmHg) and diabetes mellitus (glycemia > 120 mg/dl). The results found were the following: 1--the average number of risk factors was significant by greater among men than among women, for the age groups below 50 years of age (p < 0.01): between 50 and 55 years of age they were equal for the two groups, reaching their greatest value at 60 years of age with a sharp reduction after this latter age as regard the men but presenting a constant gradual increase for the women; 2--the average number of risk factors increased with age for both sexes (p < 0.01); 3--the prevalences of high risk hypercholesterolemias together with hypertriglyceridemia (> = 250 mg/dl) were significantly greater in the classes of higher socio-economic level; 4--the lipemic profile associated with lipemic disorders show that these latter rarely occur with just one constituent in isolation; 5--when the high-risk hypercolesterolemias are added to the borderline cases accompanied by two or more risk factors and hypertriglyceridemia they give a total of 39.2% of men and 32.8% of women, that is to say, 35.4% of the sample need immediate clinical-educational intervention.

[Atherosclerotic cardiovascular diseases, dyslipidemia, hypertension, obesity, and diabetes mellitus in a population of the metropolitan area of southeastern Brazil. I--Research methodology]. / Doenças cardiovasculares ateroscleróticas, dislipidemias, hipertensão, obesidade e diabetes melito em população da área metropolitana da região sudeste do Brasil. I--Metodologia da pesquisa.

An epidemiological study was carried out into the risk factors for the following atherosclerotic cardiovascular diseases: lipemic disorders, obesity, hypertension, diabetes mellitus as related to some factors which characterize life-style (sedentary, drinking, smoking and eating habits). The population studied belongs to the metropolitan area of S. Paulo. The research project had the following objectives: a) the development of an epidemiological baseline for the study of the risk factors for the atherosclerotics cardiovascular diseases represented by the lipimic disorders, obesity, hypertension and diabetes mellitus and their relationship with personal, family and social characteristics; b) the for clinical-educative treatment of patients or people at risk. In view of the objectives above it was decided that the project should in an integrated way with the local health centers and community associations in the field work phase. For this purpose, the methodology adopted was that of establishing small geographical areas, denominated "study areas", in accordance with socioeconomic criterion. Clinico-biochemical and eating surveys were carried out and interviews held with a view to obtaining data on socioeconomic and demographic and life-style characteristics. The clinical survey collected data on anthropometric measurements, arterial pressure, electrocardiogram and symptoms of heart disease. The biochemical survey consisted of the measurement of the following constituents of the blood: total cholesterol, HDL cholesterol, triglyceride, magnesium, glucose, sodium, potassium and phosphorous. The eating survey covered data of historic food consumption. By means of indicators such as income, schooling, occupation, position held in the occupation, ownership of property and respective size of property and employment of labour, the social classes were established. The clinico-educative intervention was carried out in the following way: a) the team made contact with the community associations and the health centers, that begin to participate in the project, permitting the use of their physical space for the carrying out of surveys and clinical exams and taking part in the work of publishing and explaining the project; b) those individuals with positive diagnosis or who are found at risk were referred to the health centers which then include assistance for the diseases in question in their permanent activities. After the end the project the team gave to the community a report on the prevalence of the morbidities researched in their population.