The value of ACR, European, Korean, and ATA ultrasound risk stratification systems combined with RAS mutations for detecting thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules.

PURPOSE: The aim of this study was to evaluate the diagnostic value of four commonly utilized ultrasound (US) RSSs, namely, the American College of Radiology [ACR], European [EU], Korean [K] TI-RADSs and American Thyroid Association [ATA] US-based RSS criteria, in combination with activating point mutations of the RAS genes (NRAS, HRAS, and KRAS) for detection of thyroid carcinoma in cytologically indeterminate and suspicious for malignancy thyroid nodules. METHODS: We retrospectively analyzed cytologically indeterminate and suspicious for malignancy thyroid nodules which underwent US, molecular testing and surgery between September 1, 2018, and December 31, 2023. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC, 95% confidence interval [CI]) was calculated. RESULTS: A total of 100 cytologically indeterminate and 24 suspicious for malignancy thyroid nodules were analyzed. Compared to the four US-based RSSs alone, the diagnostic value of the four US-based RSSs combined with RAS mutations did not significantly improved (cytologically indeterminate, AUC [95% CI] 0.6 [0.5-0.7] and 0.6 [0.5-0.7], respectively, p = 0.70; cytologically suspicious for malignancy, AUC [95% CI] 0.7 [0.5-0.9] and 0.8 [0.6-0.9], respectively, p = 0.23). CONCLUSIONS: The diagnostic value of the four main US-based RSSs (ACR, EU, K, and ATA) was not improved in conjunction with the evaluation of RAS mutations for preoperative risk stratification of cytologically indeterminate thyroid nodules. CLINICAL RELEVANCE STATEMENT: In cytologically indeterminate nodules categorized according to US-based RSSs, isolated RAS positivity does not reliably distinguish between benignity and malignancy.

Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.

Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer's disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.

Mediterranean Diet and Thyroid: An Interesting Alliance.

The Mediterranean diet, recognized as being cultural heritage by UNESCO, is mostly plant-based and includes a high consumption of whole-grain, fruit, and vegetables with a moderate consumption of alcohol during meals. Thus, it provides a small amount of saturated fatty acids and a high quantity of antioxidants and fiber. For this reason, it has been considered to have an important role in preventing cardiovascular diseases, chronic kidney diseases, type 2 diabetes mellitus, and cancer, but its relationship with thyroid function and diseases is still under debate. The aim of this review was to search for the possible correlation between the Mediterranean diet and thyroid function, and to critically evaluate the pathophysiological link between selected food intake and thyroid disorders.

Repeat thyroid FNAC: Inter-observer agreement among high- and low-volume centers in Naples metropolitan area and correlation with the EU-TIRADS.

Our institution (University Hospital "L. Vanvitelli" - Naples, Italy) is a high-volume (HV) center in Naples metropolitan area and many patients are referred there to repeat thyroid fine-needle aspiration cytology (FNAC) after initial FNAC performed in low-volume institutions (LV). The aims of the study were to 1) examine the inter-observer agreement between HV and LV institutions according to the Italian thyroid cytology system, and 2) explore how the discordant FNAC reports were distributed in the European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories. All consecutive cases of repeat FNAC performed at University Hospital "L. Vanvitelli" from January 2016 to December 2021 were retrospectively reviewed. Fleiss' kappa (κ) was used to assess the inter-observer agreement, and categorical variables were compared by chi-square testing. P < 0.05 was considered statistically significant. A total of 124 nodules from 124 adults (mean age 49 years; mean maximum diameter 19 mm) were evaluated. Initial FNAC reports at LV were: 4 (3.2%) TIR1c, 64 (51.6%) TIR2, 48 (38.7%) TIR3A, 8 (6.5%) TIR3B, 0 TIR4, 0 TIR5. The overall FNAC reports were significantly different between the LV and HV institutions. At repeated FNAC, cytological diagnosis was unchanged in 64 (51.6%) cases including TIR2 and TIR3A results. A downgraded FNAC diagnosis (i.e., TIR2 vs TIR3A, TIR2 vs TIR3B) was observed in 36 (29%) nodules. An upgraded FNAC diagnosis (i.e., TIR3B vs TIR2, TIR3B vs TIR3A, TIR4 vs TIR3A, TIR5 vs TIR2, TIR5 vs TIR3B) was recorded in 24 (19.4%) nodules. The weighted inter-observer agreement between LV and HV institutions was poor (κ=0.133). Changed FNAC results were significantly (p=0.0023) more frequent in nodules at intermediate/high-risk (i.e., EU-TIRADS 4/5) than in those at no/low risk (EU-TIRADS 2/3) [i.e., 32/48 (66.7%) and 28/76 (36.8%), respectively]. Downgraded FNAC results were significantly more frequent in EU-TIRADS 2/3 (p=0.001) while upgraded FNAC were present only in EU-TIRADS 4/5 (24/24, 100.0%). The inter-observer agreement among LV and HV thyroid services was poor. The EU-TIRADS 4 and 5 categories included all the malignant nodules with FNAC results reclassified as higher risk (i.e., TIR3B-TIR4-TIR5) by the high-volume cytology service.

Exploring the Performance of Ultrasound Risk Stratification Systems in Thyroid Nodules of Pediatric Patients.

Neck ultrasound (nUS) is the cornerstone of clinical management of thyroid nodules in pediatric patients, as well as adults. The current study was carried out to explore and compare the diagnostic performance of the main US-based risk stratification systems (RSSs) (i.e., the American College of Radiology (ACR), European (EU), Korean (K) TI-RADSs and ATA US RSS criteria) for detecting malignant thyroid lesions in pediatric patients. We conducted a retrospective analysis of consecutive children and adolescents who received a diagnosis of thyroid nodule. We included subjects with age <19 years having thyroid nodules with benign cytology/histology or final histological diagnosis. We excluded subjects with (a) a previous malignancy, (b) a history of radiation exposure, (c) cancer genetic susceptibility syndromes, (d) lymph nodes suspicious for metastases of thyroid cancer at nUS, (e) a family history of thyroid cancer, or (f) cytologically indeterminate nodules without histology and nodules with inadequate cytology. We included 41 nodules in 36 patients with median age 15 years (11-17 years). Of the 41 thyroid nodules, 29 (70.7%) were benign and 12 (29.3%) were malignant. For both ACR TI-RADS and EU-TIRADS, we found a sensitivity of 41.7%. Instead, for both K-TIRADS and ATA US RSS, we found a sensitivity of 50%. The missed malignancy rate for ACR-TIRADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 50%. The unnecessary FNA prevalence for ACR TI-RADS and EU-TIRADS was 58.3%, while that for K-TIRADS and ATA US RSS was 76%. Our findings suggest that the four US-based RSSs (i.e., ACR-TIRADS, EU-TIRADS, K-TIRADS, and ATA US RSS) have suboptimal performance in managing pediatric patients with thyroid nodules, with one-half of cancers without indication for FNA according to their recommendations.

Renal and metabolic effects of SGLT-2i and DPP-4i according to basal estimated glomerular filtration rate: Analysis from GIOIA, an observational prospective study.

In the GIOIA study, users of both SGLT-2i and DPP-4i improved glycometabolic control, after 12 months, independently from baseline eGFR levels. Moreover, both classes led to a significant decrease in eGFR in participants with eGFR ≥ 90 ml/min/1.73 m2 and no deterioration in case of mild impairment of renal function.

Hypothalamic-Pituitary Autoimmunity in Patients Treated with Anti-PD-1 and Anti-PD-L1 Antibodies.

BACKGROUND: Autoimmune hypophysitis is a frequent immune-related adverse event (irAE) in cancer patients treated with immunecheckpoint inhibitors. Studies seeking anti-pituitary (APA) and anti-hypothalamus (AHA) antibodies in patients treated with anti-PD-1 and anti-PD-L1 are scarce. The aim of this study is to search for APA and AHA and related pituitary dysfunction in patients treated with these agents. METHODS: Cross-sectional and preliminary longitudinal studies were conducted at the Medical Oncology Unit and Endocrinology and Metabolic Diseases Unit of the University of Campania "Luigi Vanvitelli". Fifty-four cancer patients on treatments with anti-PD-1 or anti-PD-L1 (Group 1) and 50 healthy controls were enrolled for a cross-sectional study; 13 cancer patients (Group 2) were enrolled for our preliminary longitudinal study. APA/AHA titers and changes in biochemical and hormonal profile were evaluated in Group 1; in Group 2, they were evaluated before and after nine weeks from the start of immunotherapy. RESULTS: Patients of Group 1 showed a higher prevalence of APA and AHA than controls: 21 of them had APA, 16 had AHA, and 11 had both autoantibodies. In total, 7 of 13 patients in Group 2 became APA-positive and 3 became AHA-positive after nine weeks of immunotherapy, showing an increase in prolactin and a decrease in ACTH and IGF-1 levels compared with basal values. CONCLUSIONS: Anti-pituitary and anti-hypothalamus antibodies seem to play a pivotal role in hypothalamic-pituitary autoimmunity and secondary endocrine-related alterations evoked by anti-PD-1 and PD-L1 antibodies.

Hypothalamic-Pituitary Autoimmunity and Related Impairment of Hormone Secretions in Chronic Fatigue Syndrome.

CONTEXT: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severe chronic illness that reduces the quality of life. A potential role of neuroendocrine autoimmune dysfunction has been hypothesized. OBJECTIVE: This work aims to investigate the occurrence of antipituitary (APA) and antihypothalamic (AHA) antibodies and possible related hypothalamic/pituitary dysfunctions in ME/CSF patients. METHODS: This is a case-control study conducted in a university hospital setting (Stanford, California, USA; and Naples, Italy). Thirty women with ME/CSF (group 1) diagnosed according to Fukuda, Canadian, and Institute of Medicine criteria, at Stanford University, were enrolled and compared with 25 age-matched healthy controls. APA and AHA were detected by immunofluorescence; moreover, we investigated hormonal secretions of anterior pituitary and respective target glands. APA and AHA titers both were assessed and the prevalence of pituitary hormone deficiencies was also investigated. RESULTS: Patients in group 1 showed a high prevalence of AHA (33%) and APA (56%) and significantly lower levels of adrenocorticotropin (ACTH)/cortisol, and growth hormone (GH) peak/insulin-like growth factor-1 (IGF-1) vs controls (all AHA/APA negative). Patients in group 1A (13 patients positive at high titers, ≥ 1:32) showed ACTH/cortisol and GH peak/IGF-1 levels significantly lower and more severe forms of ME/CFS with respect to patients in group 1B (7 positive at middle/low titers, 1:16-1:8) and 1C (10 antibody-negative patients). CONCLUSION: Both AHA and/or APA at high titers were associated with hypothalamic/pituitary dysfunction, suggesting that hypothalamic/pituitary autoimmunity may play an important role in the manifestations of ME/CFS, especially in its more severe forms.

Chronothyroidology: Chronobiological Aspects in Thyroid Function and Diseases.

Chronobiology is the scientific discipline which considers biological phenomena in relation to time, which assumes itself biological identity. Many physiological processes are cyclically regulated by intrinsic clocks and many pathological events show a circadian time-related occurrence. Even the pituitary-thyroid axis is under the control of a central clock, and the hormones of the pituitary-thyroid axis exhibit circadian, ultradian and circannual rhythmicity. This review, after describing briefly the essential principles of chronobiology, will be focused on the results of personal experiences and of other studies on this issue, paying particular attention to those regarding the thyroid implications, appearing in the literature as reviews, metanalyses, original and observational studies until 28 February 2021 and acquired from two databases (Scopus and PubMed). The first input to biological rhythms is given by a central clock located in the suprachiasmatic nucleus (SCN), which dictates the timing from its hypothalamic site to satellite clocks that contribute in a hierarchical way to regulate the physiological rhythmicity. Disruption of the rhythmic organization can favor the onset of important disorders, including thyroid diseases. Several studies on the interrelationship between thyroid function and circadian rhythmicity demonstrated that thyroid dysfunctions may affect negatively circadian organization, disrupting TSH rhythm. Conversely, alterations of clock machinery may cause important perturbations at the cellular level, which may favor thyroid dysfunctions and also cancer.

Antibiotic resistance in diabetic foot infection: how it changed with COVID-19 pandemic in a tertiary care center.

AIM: To investigate the rate of antibiotic resistance and its main risk factors in a population of patients with diabetic foot infection (DFI) during the COVID-19 pandemic, in comparison with the population of 2019. METHODS: Two hundred and twenty-five patients with DFI were admitted in a tertiary care center from January 2019 to December 2020. Antibiotic resistance was evaluated by microbiological examination of soft tissues' or bone's biopsy. RESULTS: Compared with 2019 group (n = 105), 2020 group (n = 120) had a significantly higher prevalence of antibiotic resistance [2019 vs 2020, 36% vs 63%, P <0.001] and more often was admitted with recent or current antibiotic therapy (18% vs 52%, P <0.001), which was frequently self-administered (5% vs 30%, P = 0.032). The risk of antibiotic resistance was also higher in 2020 group [OR 95% CI, 2.90 (1.68 to 4.99)]. Prior hospitalization, antibiotic self-administration and antibiotic prescription by general practitioners resulted as independent predictors of antibiotic resistance. CONCLUSIONS: In a population of people with DFI admitted in a tertiary care center during the COVID-19 pandemic the prevalence of antibiotic resistance was higher than 2019. Previous hospitalization, antibiotic self-administration /prescription by general practitioners were related to higher risk of antibiotic resistant infections.

Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease.

CONTEXT: An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD). OBJECTIVE: The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH). DESIGN: Five-year longitudinal observational study. SETTING: Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli". PATIENTS: Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only. INTERVENTION: A GFD was started in patients in group 1 after the diagnosis of CD. MAIN OUTCOME MEASURES: APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up. RESULTS: Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012). CONCLUSION: In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.

Antibodies Against Hypothalamus and Pituitary Gland in Childhood-Onset Brain Tumors and Pituitary Dysfunction.

Purpose: To detect the presence of antipituitary (APA) and antihypothalamus antibodies (AHA) in subjects treated for brain cancers, and to evaluate their potential association with pituitary dysfunction. Methods: We evaluated 63 patients with craniopharyngioma, glioma, and germinoma treated with surgery and/or radiotherapy and/or chemotherapy at a median age of 13 years. Forty-one had multiple pituitary hormone deficiencies (MPHD), six had a single pituitary defect. GH was the most common defect (65.1%), followed by AVP (61.9%), TSH (57.1%), ACTH (49.2%), and gonadotropin (38.1%). APA and AHA were evaluated by simple indirect immunofluorescence method indirect immunofluorescence in patients and in 50 healthy controls. Results: Circulating APA and/or AHA were found in 31 subjects (49.2%) and in none of the healthy controls. In particular, 25 subjects out of 31 were APA (80.6%), 26 were AHA (83.90%), and 20 were both APA and AHA (64.5%). Nine patients APA and/or AHA have craniopharyngioma (29%), seven (22.6%) have glioma, and 15 (48.4%) have germinoma. Patients with craniopharyngioma were positive for at least one antibody in 39.1% compared to 33.3% of patients with glioma and to 78.9% of those with germinoma with an analogous distribution for APA and AHA between the three tumors. The presence of APA or AHA and of both APA and AHA was significantly increased in patients with germinoma. The presence of APA (P = 0.001) and their titers (P = 0.001) was significantly associated with the type of tumor in the following order: germinomas, craniopharyngiomas, and gliomas; an analogous distribution was observed for the presence of AHA (P = 0.002) and their titers (P = 0.012). In addition, we found a significant association between radiotherapy and APA (P = 0.03). Conclusions: Brain tumors especially germinoma are associated with the development of hypothalamic-pituitary antibodies and pituitary defects. The correct interpretation of APA/AHA antibodies is essential to avoid a misdiagnosis of an autoimmune infundibulo-neurohypophysitis or pituitary hypophysitis in patients with germinoma.

Impact of Pituitary Autoimmunity and Genetic Disorders on Growth Hormone Deficiency in Children and Adults.

Growth hormone (GH), mostly through its peripheral mediator, the insulin-like growth factor 1(IGF1), in addition to carrying out its fundamental action to promote linear bone growth, plays an important role throughout life in the regulation of intermediate metabolism, trophism and function of various organs, especially the cardiovascular, muscular and skeletal systems. Therefore, if a prepubertal GH secretory deficiency (GHD) is responsible for short stature, then a deficiency in adulthood identifies a nosographic picture classified as adult GHD syndrome, which is characterized by heart, muscle, bone, metabolic and psychic abnormalities. A GHD may occur in patients with pituitary autoimmunity; moreover, GHD may also be one of the features of some genetic syndromes in association with other neurological, somatic and immune alterations. This review will discuss the impact of pituitary autoimmunity on GHD and the occurrence of GHD in the context of some genetic disorders. Moreover, we will discuss some genetic alterations that cause GH and IGF-1 insensitivity and the arguments in favor and against the influence of GH/IGF-1 on longevity and cancer in the light of the papers on these issues that so far appear in the literature.

EMPATHY: A New Tool for Identifying the Most Suitable Thyroxine Formulation in Hypothyroid Patients.

Background: Therapy of hypothyroidism is based on the administration of appropriate doses of levothyroxine (LT4). A failure to achieve the thyrotropin (TSH) target may be due to poor compliance with the LT4 therapy in about 60% of cases or to malabsorption in about 40% of cases. No tools are available for detecting malabsorption disorders before the choice of the most appropriate therapy. The aim of this study was to validate the Evaluation of Malabsorption in PATients with HYpothyroidism (EMPATHY) questionnaire and to demonstrate its usefulness in indicating the most appropriate therapy. Methods: EMPATHY consists of seven questions that allow the evaluation of several intolerances and allergies. Three hundred (100 males) newly diagnosed hypothyroid patients were enrolled and randomly assigned to complete an EMPATHY questionnaire (150 patients; group 1) or to a control group (150 patients; group 2). The choice of thyroxine formulation and dose for each group was made on the basis of the questionnaire answers or based on the history. Thyroid hormones and TSH were evaluated at enrollment and then every two months for six months; the number of the dose adjustments in the six months for each patient was recorded. Results: Of the 150 patients in each group, 21 (14%) in group 1 and 42 (28%) in group 2 (p = 0.005) needed more than two dose adjustments within six months. After six months of replacement therapy, six (4%) patients in group 1 and 17 (11%) in group 2 (p = 0.03) did not have appropriately controlled hypothyroidism (TSH ≥2.5 mIU/L). A significantly higher LT4 final dose was found in group 2 (148 ± 33 µg/day) than in group 1 (136 ± 28 µg/day; p = 0.003). Conclusions: Validation of EMPATHY provides endocrinologists with a useful tool in clinical practice, permitting a better personalization of LT4 replacement therapy, a more rapid attainment of the target TSH levels, and a decreased need for dose adjustments after initiating therapy.

Diabetes and Aging: From Treatment Goals to Pharmacologic Therapy.

Diabetes is becoming one of the most widespread health burning problems in the elderly. Worldwide prevalence of diabetes among subjects over 65 years was 123 million in 2017, a number that is expected to double in 2045. Old patients with diabetes have a higher risk of common geriatric syndromes, including frailty, cognitive impairment and dementia, urinary incontinence, traumatic falls and fractures, disability, side effects of polypharmacy, which have an important impact on quality of life and may interfere with anti-diabetic treatment. Because of all these factors, clinical management of type 2 diabetes in elderly patients currently represents a real challenge for the physician. Actually, the optimal glycemic target to achieve for elderly diabetic patients is still a matter of debate. The American Diabetes Association suggests a HbA1c goal <7.5% for older adults with intact cognitive and functional status, whereas, the American Association of Clinical Endocrinologists (AACE) recommends HbA1c levels of 6.5% or lower as long as it can be achieved safely, with a less stringent target (>6.5%) for patients with concurrent serious illness and at high risk of hypoglycemia. By contrast, the American College of Physicians (ACP) suggests more conservative goals (HbA1c levels between 7 and 8%) for most older patients, and a less intense pharmacotherapy, when HbA1C levels are ≤6.5%. Management of glycemic goals and antihyperglycemic treatment has to be individualized in accordance to medical history and comorbidities, giving preference to drugs that are associated with low risk of hypoglycemia. Antihyperglycemic agents considered safe and effective for type 2 diabetic older patients include: metformin (the first-line agent), pioglitazone, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists. Insulin secretagogue agents have to be used with caution because of their significant hypoglycemic risk; if used, short-acting sulfonylureas, as gliclazide, or glinides as repaglinide, should be preferred. When using complex insulin regimen in old people with diabetes, attention should be paid for the risk of hypoglycemia. In this paper we aim to review and discuss the best glycemic targets as well as the best treatment choices for older people with type 2 diabetes based on current international guidelines.

The role of autoimmunity in pituitary dysfunction due to traumatic brain injury.

PURPOSE: Traumatic brain injury (TBI) is one of the most common causes of mortality and long-term disability and it is associated with an increased prevalence of neuroendocrine dysfunctions. Post-traumatic hypopituitarism (PTHP) results in major physical, psychological and social consequences leading to impaired quality of life. PTHP can occur at any time after traumatic event, evolving through various ways and degrees of deficit, requiring appropriate screening for early detection and treatment. Although the PTHP pathophysiology remains to be elucitated, on the basis of proposed hypotheses it seems to be the result of combined pathological processes, with a possible role played by hypothalamic-pituitary autoimmunity (HPA). This review is aimed at focusing on this possible role in the development of PTHP and its potential clinical consequences, on the basis of the data so far appeared in the literature and of some results of personal studies on this issue. METHODS: Scrutinizing the data so far appeared in literature on this topic, we have found only few studies evaluating the autoimmune pattern in affected patients, searching in particular for antipituitary and antihypothalamus autoantibodies (APA and AHA, respectively) by simple indirect immunofluorescence. RESULTS: The presence of APA and/or AHA at high titers was associated with an increased risk of onset/persistence of PTHP. CONCLUSIONS: HPA seems to contribute to TBI-induced pituitary damage and related PTHP. However, further prospective studies in a larger cohort of patients are needed to define etiopathogenic and diagnostic role of APA/AHA in development of post-traumatic hypothalamic/pituitary dysfunctions after a TBI.

Metabolic syndrome and cancer: "The common soil hypothesis".

Metabolic syndrome (MetS) and cancer share many modifiable risk factors including age, genetic factors, obesity, physical inactivity, unhealthy diet, alcohol, smoking, endocrine disruptors exposure, circadian clock disturbances, and air pollution. MetS is closely linked to cancer, as it increases cancer risk and cancer-related mortality; moreover, cancer survivors have an increased risk of MetS. Elucidating the mechanisms linking MetS to cancer is important to prevent or delay these two conditions. Possible mechanisms explaining the relationship between MetS and cancer include hyperinsulinemia and alterations of insulin-like growth factor system, chronic subclinical inflammation, abnormalities in sex hormones metabolism and adipokines, hyperglicemia, alterations in both gene expression and hormonal profile by endocrine disruptors and air pollution, desynchronization of circadian clock. The common soil hypothesis claims that MetS may be considered a surrogate marker for dietary risk factors of cancer, and a warning sign for susceptible individuals exposed to an unhealthy diet. The common soil hypothesis and the clepsydra of foods represent a theoretical substrate to preventive intervention strategies against the pandemics of MetS and cancer: adherence to healthy dietary patterns is associated with a reduced risk of MetS, and improvement of the quality of diet is consistently associated with a reduction in cancer-related mortality.

Gender-differences in glycemic control and diabetes related factors in young adults with type 1 diabetes: results from the METRO study.

PURPOSE: To describe gender differences concerning glycemic control, cardiovascular risk factors, diabetic complications, concomitant pathologies, and circulating endothelial progenitor cells (EPCs), in a population of young adults with type 1 diabetes. METHODS: We collected data from 300 consecutively patients (168 males and 132 females), aged 18-30 years, among those admitted at Diabetes Unit of University of Campania "Luigi Vanvitelli" (Naples, Italy) from March 2012 to January 2017. Circulating levels of seven EPCs phenotypes were determined by flow cytometry. RESULTS: As compared to men, women with type 1 diabetes had a significantly higher HbA1c levels (%, 8.4 ± 1.3 vs. 8.1 ± 1.3, P = 0.020), body mass index (Kg/m2, 24.8 ± 4.2 vs. 23.9 ± 3.9, P = 0.034), HDL-cholesterol (mg/dL, 61.7 ± 13.7 vs. 54.7 ± 13.9, P < 0.001), and a lower count of both CD133+KDR+ and CD34+KDR+CD133+ EPCs (P = 0.022, P < 0.001, respectively). A higher proportion of women had overweight/obesity, and thyroiditis; smoking and sexual dysfunctions were more prevalent in men than in women. CONCLUSIONS: Young adults with type 1 diabetes present gender differences with regard to glycemic control, prevalence of some cardiovascular risk factors, sexual dysfunctions and circulating levels of EPCs, most often to the detriment of women.

Particulate matter air pollution: individual choices for improving cardiometabolic well-being.

Exposure to small particulate matter (PM2.5) has become the 5th highest ranking risk factor for death, responsible for 4.2 million deaths worldwide. PM pollution is also associated with cardiovascular disease and type 2 diabetes, and may contribute to deteriorate the already poor cardiometabolic outlook of the diabetic patient. Although most sources of outdoor air pollution are well beyond the control of individuals, there is still room for personal action. Health behaviors (smoking cessation, avoiding obesity, and increasing physical activity) may increase the poor life expectancy of individuals in the lowest income quartile of the Western population; moreover, a favorable lifestyle, (no current smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern), may cut by nearly 50% the risk of coronary heart disease among people at high genetic risk. Things seem not immutable, as individual healthy choices do matter.

Lifestyle recommendations for the prevention and management of metabolic syndrome: an international panel recommendation.

The importance of metabolic syndrome (MetS) lies in its associated risk of cardiovascular disease and type 2 diabetes, as well as other harmful conditions such as nonalcoholic fatty liver disease. In this report, the available scientific evidence on the associations between lifestyle changes and MetS and its components is reviewed to derive recommendations for MetS prevention and management. Weight loss through an energy-restricted diet together with increased energy expenditure through physical activity contribute to the prevention and treatment of MetS. A Mediterranean-type diet, with or without energy restriction, is an effective treatment component. This dietary pattern should be built upon an increased intake of unsaturated fat, primarily from olive oil, and emphasize the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, as well as moderate consumption of alcohol. Other dietary patterns (Dietary Approaches to Stop Hypertension, new Nordic, and vegetarian diets) have also been proposed as alternatives for preventing MetS. Quitting smoking and reducing intake of sugar-sweetened beverages and meat and meat products are mandatory. Nevertheless, there are inconsistencies and gaps in the evidence, and additional research is needed to define the most appropriate therapies for MetS. In conclusion, a healthy lifestyle is critical to prevent or delay the onset of MetS in susceptible individuals and to prevent cardiovascular disease and type 2 diabetes in those with existing MetS. The recommendations provided in this article should help patients and clinicians understand and implement the most effective approaches for lifestyle change to prevent MetS and improve cardiometabolic health.