"Time" for obesity-related cancer: The role of the circadian rhythm in cancer pathogenesis and treatment.

The circadian rhythm is regulated by an intrinsic time-tracking system, composed both of a central and a peripheral clock, which influences the cycles of activities and sleep of an individual over 24 h. At the molecular level, the circadian rhythm begins when two basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins, BMAL-1 and CLOCK, interact with each other to produce BMAL-1/CLOCK heterodimers in the cytoplasm. The BMAL-1/CLOCK target genes encode for the repressor components of the clock, cryptochrome (Cry1 and Cry2) and the Period proteins (Per1, Per2 and Per3). It has been recently demonstrated that the disruption of circadian rhythm is associated with an increased risk of developing obesity and obesity-related diseases. In addition, it has been demonstrated that the disruption of the circadian rhythm plays a key role in tumorigenesis. Further, an association between the circadian rhythm disruptions and an increased incidence and progression of several types of cancer (e.g., breast, prostate, colorectal and thyroid cancer) has been found. As the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) and at the same time tumor promoter functions, this manuscript has the aim to report how the aberrant circadian rhythms affect the development and prognosis of different types of obesity-related cancers (breast, prostate, colon rectal and thyroid cancer) focusing on both human studies and on molecular aspects.

Sex-differences in Mediterranean diet: a key piece to explain sex-related cardiovascular risk in obesity? A cross-sectional study.

BACKGROUND: Mediterranean Diet (MD) has many health benefits, particularly in reducing cardiovascular risk (CVR). However, it is still little known if there are any sex differences in following this nutritional pattern and, thus, the potential sex-related repercussions on CVR in obesity. The study aimed to characterize sex-related adherence to MD and its association with CVR factors in subjects with obesity. METHODS: A total of 968 females (33.81 ± 11.06 years; BMI 34.14 ± 7.43 kg/m2) and 680 males (aged 34.77 ± 11.31years; BMI 33.77 ± 8.13 kg/m2) were included in a cross-sectional observational study. Lifestyle habits, anthropometric parameters, high sensitivity C-reactive protein (hs-CRP), and adherence to MD were evaluated. RESULTS: Females had significantly higher adherence to MD and lower hs-CRP levels than males (p < 0.001). Additionally, females consumed significantly more vegetables, fruits, legumes, fish/seafood, nuts, and sofrito sauce and less quantity of olive oil, butter, cream, margarine, red/processed meats, soda drinks (p = 0.001), red wine, and commercial sweets and confectionery than their counterparts. A PREDIMED score of ≤ 6 was associated with a significantly increased CVR in both sexes. CONCLUSIONS: Females had higher adherence to MD, lower CVR, and different food preferences than males. Although the same PREDIMED threshold has been identified as a spy of CVR, the sex-related preference of individual foods included in the MD could explain the different impact of this nutritional pattern on CVR in both sexes.

Very low-calorie ketogenic diet (VLCKD): a therapeutic nutritional tool for acne?

BACKGROUND: Acne, a chronic inflammatory disease impacting the pilosebaceous unit, is influenced significantly by inflammation and oxidative stress, and is commonly associated with obesity. Similarly, obesity is also associated with increased inflammation and oxidation. The role of diet in acne remains inconclusive, but the very low-calorie ketogenic diet (VLCKD), known for weight loss and generating anti-inflammatory ketone bodies, presents promising potential. Despite this, the effects of VLCKD on acne remain underexplored. This study aimed to investigate the efficacy of a 45-day active phase of VLCKD in reducing the clinical severity of acne in young women with treatment-naïve moderate acne and grade I obesity. METHODS: Thirty-one women with treatment-naïve moderate acne, grade I obesity (BMI 30.03-34.65 kg/m2), aged 18-30 years, meeting inclusion/exclusion criteria, and consenting to adhere to VLCKD were recruited. Baseline and post-intervention assessments included anthropometric measurements, body composition, phase angle (PhA), trimethylamine N-oxide (TMAO) levels, and reactive oxygen metabolite derivatives (dROMs) as markers of inflammation, dysbiosis, and oxidative stress, respectively. A comprehensive dermatological examination, incorporating the Global Acne Grading System (GAGS) and the Dermatology Life Quality Index (DLQI), was conducted for all women. RESULTS: VLCKD resulted in general improvements in anthropometric and body composition parameters. Significantly, there were significant reductions in both the GAGS score (Δ%: - 31.46 ± 9.53, p < 0.001) and the DLQI score (Δ%: - 45.44 ± 24.02, p < 0.001) after the intervention. These improvements coincided with significant decreases in TMAO (p < 0.001) and dROMs (p < 0.001) levels and a significant increase in PhA (Δ%: + 8.60 ± 7.40, p < 0.001). Changes in the GAGS score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjusting for Δ% FM. Changes in the DLQI score positively correlated with changes in dROMs (p < 0.001) and negatively with PhA (p < 0.001) even after adjustment for Δ% FM. CONCLUSION: Given the side effects of drugs used for acne, there is an increasing need for safe, tolerable, and low-cost treatments that can be used for acne disease. The 45-day active phase of VLCKD demonstrated notable improvements in acne severity, and these improvements seemed to be attributable to the known antioxidant and anti-inflammatory effects of VLCKD.

Very low-calorie ketogenic diet (VLCKD) in the management of hidradenitis suppurativa (Acne Inversa): an effective and safe tool for improvement of the clinical severity of disease. Results of a pilot study.

BACKGROUND: Hidradenitis suppurativa (HS), an inflammatory-based dermatological condition often associated with obesity, poses significant challenges in management. The very low-calorie ketogenic diet (VLCKD) has shown efficacy in addressing obesity, related metabolic disorders, and reducing chronic inflammation. However, its effects on HS remain underexplored. In this prospective pilot study, we aimed to investigate the impact of a 28-day active phase of VLCKD on HS in a sample of treatment-naive women with HS and excess weight. METHODS: Twelve women with HS and overweight or obesity (BMI 27.03 to 50.14 kg/m2), aged 21 to 54 years, meeting inclusion/exclusion criteria and agreeing to adhere to VLCKD, were included. Baseline lifestyle habits were assessed. The Sartorius score was used to evaluate the clinical severity of HS. Anthropometric parameters (waist circumference, weight, height, and body mass index), body composition via bioelectrical impedance analysis, levels of trimethylamine N-oxide (TMAO), oxidized low-density lipoprotein (oxLDL), and derivatives of reactive oxygen metabolites (dROMs) were assessed at baseline and after 28 days of the active phase of VLCKD. RESULTS: VLCKD led to general improvements in anthropometric parameters and body composition. Notably, a significant reduction in the Sartorius score was observed after the intervention (Δ%: - 24.37 ± 16.64, p < 0.001). This reduction coincided with significant decreases in TMAO (p < 0.001), dROMs (p = 0.001), and oxLDL (p < 0.001) levels. Changes in the Sartorius score exhibited positive correlations with changes in TMAO (p < 0.001), dROMs (p < 0.001), and oxLDL (p = 0.002). CONCLUSION: The 28-day active phase of VLCKD demonstrated notable improvements in HS severity and associated metabolic markers, highlighting the potential utility of VLCKD in managing HS and its association with metabolic derangements in women with overweight or obesity.

Vein wall thickness and severity of pulmonary involvement due to sars n-cov2 virus infection.

BACKGROUND: An observational study involving patients recovered from COVID-19 was conducted in order to evaluate the presence/absence of vein wall thickness increasing, according to the severity of pulmonary involvement quantified with a CT-scoring system. METHODS: The venous wall thickness (VWT) of 31 patients (23 males and 8 females) with COVID 19 previously admitted to Federico II University Hospital of Naples was evaluated through ultrasound measurement of the common femoral Vein 1 cm proximal to the saphenous-femoral junction and the popliteal Vein 1 cm distal to the confluence of gemellary veins. Measurements were taken with an automated tool to avoid human error. All patients were evaluated in the supine position. Patients were then stratified into two groups, VWT > 1 mm and VWT < 1 mm. Lung damage was assessed through thoracic High Resolution Computer Tomography and subsequently quantified using the scoring system set out by Chung et al. CEAP-C class was calculated for all patients. RESULTS: The mean value of COVID score in VWT > 1 mm group was 7.4 (S.D. 4.83), whilst the mean value of the COVID score in the VWT < 1 mm group was 3.82 (S.D 3.34). These findings were determined to be statistically significant in a two-tie Student-T test. The linear regression test between VWT and Covid score values demonstrated a direct relationship between the two variables. CONCLUSION: These results demonstrate a link between two different aspects of the pathological effects on the vessels during a SARS-COV 2 infection. As such a common primum movens can be hypothesized in both micro-thrombotic and inflammatory processes relating to COVID 19.

Prolactin effects on the pathogenesis of diabetes mellitus.

BACKGROUND: Prolactin (PRL) is a pituitary hormone promoting lactation in response to the suckling reflex. Beyond its well-known effects, novel tissue-specific and metabolic functions of PRL are emerging. AIMS: To dissect PRL as a critical mediator of whole-body gluco-insulinemic sensitivity. METHODS: PubMed-based search with the following terms 'prolactin', 'glucose metabolism', 'type 2 diabetes mellitus', 'type 1 diabetes mellitus', 'gestational diabetes mellitus' was performed. DISCUSSION: The identification of the PRL-glucose metabolism network poses the basis for unprecedented avenues of research in the pathogenesis of diabetes mellitus type 1 or 2, as well as of gestational diabetes. In this regard, it is of timely relevance to define properly the homeostatic PRL serum levels since glucose metabolism could be influenced by the circulating amount of the hormone. RESULTS: This review underscores the basic mechanisms of regulation of pancreatic ß-cell functions by PRL and provides a revision of articles which have investigated the connection between PRL unbalancing and diabetes mellitus. Future studies are needed to elucidate the burden and the role of PRL in the regulation of glucose metabolism and determine the specific PRL threshold that may impact the management of diabetes. CONCLUSION: A careful evaluation and context-driven interpretation of PRL levels (e.g., pregnancy, PRL-secreting pituitary adenomas, drug-related hyper- and hypoprolactinemia) could be critical for the correct screening and management of glucometabolic disorders, such as type 1 or 2 as well as gestational diabetes mellitus.

Obesogenic environments as major determinants of a disease: It is time to re-shape our cities.

Obesity rates are increasing in almost all high- and low-income countries, and population-based approaches are necessary to reverse this trend. The current global efforts are focused on identifying the root causes of obesity and developing effective methods for early diagnosis, screening, treatment, and long-term management, both at an individual and health system level. However, there is a relative lack of effective options for early diagnosis, treatment, and long-term management, which means that population-based strategies are also needed. These strategies involve conceptual shifts towards community- and environment-focused approaches. This review aimed to provide evidence on how environmental factors contribute to the risk of obesity and how reshaping cities can help slow down obesity prevalence rates and improve long-term management.

Chrononutrition in type 2 diabetes mellitus and obesity: A narrative review.

Chrononutrition is a nutritional regimen that follows our biological clock, marked by the changes in metabolism that occur during the day. This regimen includes the distribution of energy, the regularity and frequency of meals, and the importance of these factors for metabolic health. A growing body of animal and human evidence indicates that the timing of food intake throughout the day can have a significant and beneficial impact on the metabolic health and well-being of individuals. In particular, both the timing and frequency of meals have been associated with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and other chronic conditions. Today's busy lifestyle makes many people skip breakfast and eat late at night. Eating late at night has been shown to cause a circadian misalignment, with the latter having a negative impact on weight control and glucose metabolism. Additionally, some studies have found a relatively strong association between skipping breakfast and insulin resistance, and T2DM. Against the backdrop of escalating obesity and T2DM rates, coupled with the recognized influence of food timing on disease evolution and control, this review aimed to synthesize insights from epidemiological and intervention studies of the interplay of timing of food intake and macronutrient consumption, reporting their impact on obesity and T2DM.

Efficacy and tolerability of somatostatin analogues according to gender in patients with neuroendocrine tumors.

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.

Cardiometabolic effects of hypoprolactinemia.

The fall of PRL levels below the lower limit of the normal range configures the condition of hypoprolactinemia. Unlike PRL excess, whose clinical features and treatments are well established, hypoprolactinemia has been only recently described as a morbid entity requiring prompt identification and proper therapeutic approach. Particularly, hypoprolactinemia has been reported to be associated with the development of metabolic syndrome and impaired cardiometabolic health, as visceral obesity, insulin-resistance, diabetes mellitus, dyslipidaemia, chronic inflammation, and sexual dysfunction have been found more prevalent in patients with hypoprolactinemia as compared to those with normoprolactinemia. This evidence has been collected mainly in patients on chronic treatment with dopamine agonists for PRL excess due to a PRL-secreting pituitary tumour, and less frequently in those receiving the atypical antipsychotic aripiprazole. Nowadays, hypoprolactinemia appears to represent a novel and unexpected risk factor for cardiovascular diseases, as is the case for hyperprolactinemia. Nevertheless, current knowledge still lacks an accurate biochemical definition of hypoprolactinemia, since no clear PRL threshold has been established to rule in the diagnosis of PRL deficiency enabling early identification of those individual subjects with increased cardiovascular risk directly ascribable to the hormonal imbalance. The current review article focuses on the effects of hypoprolactinemia on the modulation of body weight, gluco-insulinemic and lipid profile, and provides latest knowledge about potential cardiovascular outcomes of hypoprolactinemia.

Endocrine involvement in hepatic glycogen storage diseases: pathophysiology and implications for care.

Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.g., hypothalamic­pituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment. Being aware of the endocrine abnormalities occurring in hepatic GSDs is essential (1) to provide optimized medical care to this group of individuals and (2) to drive research aiming at understanding the disease pathophysiology. In this review, a thorough description of the endocrine manifestations in individuals with hepatic GSDs is presented, including pathophysiological and clinical implications.

Gender Differences in Lung Neuroendocrine Tumors: A Single-Center Experience.

INTRODUCTION: Gender difference may affect lung neuroendocrine tumor (L-NET) onset, progression, and outcomes as emerged in other cancers. This study aimed to analyze gender difference in L-NET to identify potential prognostic factors, to improve patient follow-up and therapeutic strategies. METHODS: Patients with histologically confirmed L-NEN diagnosis referred to the ENETS CoE of the Endocrinology Unit, Federico II University of Naples, from 2013 to 2023, were retrospectively evaluated. RESULTS: Among 48 patients with L-NEN, 38 (79.2%) with sporadic L-NET were enrolled: 22 typical (57.9%) and 16 atypical (42.1%) carcinoids, 22 (57.9%) female and 16 (42.1%) male, mean age at diagnosis 57.3 years (range 16-84). Median follow-up was 70.5 months (range 12-305). No statistical difference resulted regarding smoking habit, BMI, primary site (left/right and central/peripheral), and histological characteristics, between cohorts. Metastasis at diagnosis was found in 20 patients (52.3%), 10 female (10%) and 10 male (10%) (p: 0.20). Progressive disease (PD) was observed in 14 (36.8%) patients, and male sex developed PD more frequently 9/14 (64.3%) than female 5 (35.7%), p: 0.05. Male sex seemed to show more frequently bone metastasis without reaching statistical difference, 7 male/10 (70%), p: 0.06. Among 9 deaths (23.7%), 7 (77.8%) were men and 7 died for PD, p < 0.03. Male had a poorer prognosis than female regarding progression-free survival (PFS) (p: 0.04) and overall survival (p: 0.001), also when sub-groups of patient metastatic at diagnosis were compared (p: 0.02 and p: 0.02). CONCLUSIONS: This study showed a worse prognosis in male than female with L-NET, despite similar clinical features, tumor type, stage, and treatment, with regard to PFS, OS, and metastatic spread. These findings may suggest a closer follow-up in men, with potential positive impact on outcomes.

d-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI).

BACKGROUND: d-Chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders. OBJECTIVES: This perspective seeks to explore the mechanisms and functions of d-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation. METHODS: A narrative review of all the relevant papers known to the authors was conducted. OUTCOME: d-Chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue transdifferentiation. These different modes of action have potential applications in a variety of therapeutic fields, including PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health. CONCLUSIONS: d-Chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between d-chiro-inositol and its isomer myo-inositol. The insulin-sensitizing activities of d-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

Supplementation with medium-chain fatty acids increases body weight loss during very low-calorie ketogenic diet: a retrospective analysis in a real-life setting.

BACKGROUND: Very low-calorie ketogenic diet (VLCKD) has shown to significantly reduce body weight and fat mass, as well as inflammation. These effects are supported by nutritional ketosis, which triggers the utilization of the ketone body as an energy source. Medium-chain fatty acids (MCTs) might serve as potential enhancers of ketone bodies production with a greater effect on weight loss. Nevertheless, no clinical studies have evaluated the effect of MCTs supplementation in addition to VLCKD. Therefore, the present study aimed to evaluate whether the supplementation with MCTs can induce a greater weight reduction during the ketogenic phase of VLCKD. METHODS: In this retrospective study, 263 women with overweight/obesity (body mass index, BMI: 35.7 ± 5.3 kg/m2) aged 37.5 ± 14.2 years followed one of these dietary protocols for 45 days: (a) Control group, 83 participants (31.6%) (VLCKD without MCTs), (b) VLCKD + MCTs group, 86 participants (32.7%) (MCTs supplementation - 20 g/day- during VLCKD starting from the first day of the active phase), (c) VLCKD + earlyMCTs, 94 participants (35.7%) (MCTs supplementation - 20 g/day-starting from 5 days before the beginning of the VLCKD active phase. Anthropometric measures, body composition, and c-reactive protein (CRP) concentrations were collected at the beginning and at the end (45 days) of the VLCKD intervention. RESULTS: MCTs supplementation significantly decreased body weight, BMI, and waist circumference as compared to the control group, with a greater effect in the VLCKD + earlyMCTs group. A two-fold decrease in fat mass and an increase in muscle mass were observed in the VLCKD + earlyMCTs group as compared to the control group. As for inflammation, hs-CRP concentrations (assessed as absolute percent change) were significantly lower in the VLCKD + MCTs group (p = 0.009) and the VLCKD + earlyMCTs group (p = 0.011) than in the control group. A logistic regression model showed that VLCKD + earlyMCTs increase the likelihood of improvement of BMI classes (OR: 1.85, 95% CI 1.02-3.36) also after adjusting for the potential confounding factors. CONCLUSION: MCTs supplementation (20 g/day) may be a useful tool to enhance the beneficial effect of VLCKD on the reduction of body weight and fat mass. In particular, MCTs supplementation before the beginning of the VLCKD active phase might facilitate ketosis thus contributing to the effectiveness of the nutritional intervention.

Can the ketogenic diet improve our dreams? Effect of very low-calorie ketogenic diet (VLCKD) on sleep quality.

BACKGROUND: Obesity is a condition that is often associated with sleep disorders, including reduced sleep quality (SQ). Very low calorie ketogenic diet (VLCKD) has proven to be effective in the management of obesity and associated metabolic disorders. However, little is still known about the effects of this promising nutritional protocol on SQ. Thus, the purpose of this study was to investigate the short-term effect of VLCKD on SQ in women with overweight/obesity and if any changes, to identify the predictive factor that through VLCKD modified SQ. METHODS: Were consecutively enrolled a total of 324 subjects, who met the inclusion criteria and accepted to adhere to VLCKD. Assessment of nutritional status, including anthropometric measurements (height, weight, and waist circumference), bioelectrical impedance analysis (phase-sensitive system, 50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy Akern), high sensitivity C reactive protein levels (hs-CRP), and SQ were carried out at baseline and after 31 days of active stage of VLCKD. SQ was evaluated using the validated questionnaire Pittsburgh Sleep Quality Index (PSQI). RESULTS: In addition to the expected general improvement of anthropometric parameters and body composition, VLCKD improved significantly SQ, as demonstrated by the improvement of all parameters included in the PSQI questionnaire (p < 0.001). Both at baseline and after 31 days of active stage of VLCKD, the PSQI score was significantly associated with BMI, waist circumference, fat mass, fat free mass (p < 0.001 for all) and hs-CRP (p = 0.023). PhA was negatively associated with PSQI score only at baseline (p < 0.001). ∆% PSQI positively correlated with ∆% BMI, ∆% fat mass, ∆% hs-CRP (p < 0.001 for all) and negatively correlated with ∆% fat free mass (p < 0.001), and ∆% PhA (p = 0.031). In the multiple regression analysis ∆% fat mass represented the only predictor of changes in SQ after VLCKD. Finally, in the ROC analysis, a threshold value of ∆% fat mass > - 8.4% predicted improvement in SQ (p < 0.001). CONCLUSION: In conclusion, VLCKD determines an improvement of SQ in women with overweight and obesity, that was mostly mediated by the reduction of fat mass related to this nutritional protocol.

Very low-calorie ketogenic diet (VLCKD): an antihypertensive nutritional approach.

BACKGROUND: Obesity is accompanied by hormonal, inflammatory and endothelial alterations. These alterations induce a stimulation of several other mechanisms that contribute to the hypertensive state and to increase the cardiovascular morbidity. This pilot, open - label, single- center, prospective clinical trial aimed to evaluate the effect of very low- calorie ketogenic diet (VLCKD) on blood pressure (BP) in women with of obesity and hypertension. METHODS: A total of 137 women, who met the inclusion criteria and accepted to adhere to VLCKD, were consecutively enrolled. Assessment of anthropometric parameters (weight, height, and waist circumference), body composition (through bioelectrical impedance analysis), systolic (SBP) and diastolic blood pressure (DBP) and blood sample collection were carried out at baseline and after 45 days of the active phase of VLCKD. RESULTS: After VLCKD all the women experienced a significant reduction in body weight and an overall improvement of body composition parameters. In addition, high sensitivity C reactive protein (hs- CRP) levels were significantly diminished (p < 0.001), while phase angle (PhA) increased by almost 9% (p < 0.001). Interestingly, both SBP and DBP were significantly improved (-12.89% and - 10.77%, respectively; p < 0.001). At baseline, SBP and DBP showed statistically significant correlations with body mass index (BMI), waist circumference, hs-CRP levels, PhA, total body water (TBW), extracellular water (ECW), Na / K ratio, and fat mass. Even after VLCKD, all correlations among SBP and DBP with the study variables were statistically significant, except for the association between DBP and Na / K ratio. Changes (%) in both SBP and DBP were associated with ∆BMI%, ∆PhA% and ∆hs- CRP levels (p < 0.001). In addition, only ∆SBP% was associated with ∆waist circumference (p = 0.017), ∆TBW (p = 0.017), and ∆fat mass (p < 0.001); while only ∆DBP% was associated with ∆ECW (p = 0.018), and ∆Na / K ratio (p = 0.048). After adjusting for ∆BMI, ∆WC, ∆PhA, ∆TBW, and ∆fat mass, the correlation between changes in ∆SBP and ∆hs -CRP levels remained statistically significant (p < 0.001). Similarly, the correlation between ∆DBP and ∆hs- CRP levels also remained statistically significant after adjustment for ∆BMI, ∆PhA, ∆Na / K ratio, and ∆ECW (p < 0.001). From multiple regression analysis ∆hs- CRP levels seemed to be the main predictor of changes of BP (p < 0.001). CONCLUSION: VLCKD reduces BP in women with of obesity and hypertension in a safely manner.

Adherence to the Mediterranean diet as a possible additional tool to be used for screening the metabolically unhealthy obesity (MUO) phenotype.

BACKGROUND: The terms metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) categorize subjects with obesity based on the presence or absence of cardio-metabolic risk factors. Detecting MUO phenotype is crucial due to the high risk of cardio-metabolic complications, requiring tailored and intensive follow-up. However, diagnosing MUO is time-consuming and costly. Thus, we aimed to investigate the role of Mediterranean diet (MD) in determining MHO/MUO phenotypes and whether adherence to MD could serve as an additional screening tool for MUO phenotype. METHODS: The study population of this cross-sectional observational study consisted of 275 subjects with obesity. We assessed their lifestyle habits (physical activity and smoking habits), anthropometric measurements (weight, height, waist circumference, body mass index), blood pressure, metabolic parameters, inflammatory marker (high sensitivity C reactive protein levels), adherence to MD (by PREvención con DIetaMEDiterránea (PREDIMED) questionnaire), and MHO/MUO phenotypes. RESULTS: The study included 275 individuals with obesity (256F/19M; 34.0 ± 10.5 years; BMI 38.3 ± 5.95 kg/m2). Among them, 114 (41.5%) exhibited MHO phenotype, while 161 (58.5%) had MUO phenotype. MHO phenotype exhibited favorable anthropometric and cardio-metabolic profiles, characterized by lower waist circumference (p < 0.001), BMI (p < 0.001), insulin resistance (p < 0.001), blood pressure (p < 0.001), inflammation (p < 0.001), and lipid levels (p < 0.001) compared to MUO phenotype. Notably, we found that MHO phenotype had higher adherence to MD (p < 0.001) and consumed more extra virgin olive oil (EVOO) (p < 0.001), vegetables (p < 0.001), fruits (p < 0.001), legumes (p = 0.001), fish (p < 0.001), wine (p = 0.008), and nuts (p = 0.001), while reporting lower intake of red/processed meats (p < 0.001), butter, cream, margarine (p = 0.008), soda drinks (p = 0.006), and commercial sweets (p = 0.002) compared to MUO phenotype. Adherence to MD (p < 0.001) and EVOO (p = 0.015) intake were identified as influential factors in determining the presence of MUO/MHO phenotypes. Furthermore, a PREDIMED score < 5 proved to be the most sensitive and specific cut-point value for predicting the presence of MUO phenotype (p < 0.001). CONCLUSION: High adherence to MD was associated with MHO phenotype. Moreover, we suggest that a specific cut-off of the PREDIMED score could be an indicator to discriminate patients with MUO/MHO phenotypes and therefore help in identifying patients at higher cardiovascular risk who will require specific dietary intervention.

Scientific evidence supporting the newly developed one-health labeling tool "Med-Index": an umbrella systematic review on health benefits of mediterranean diet principles and adherence in a planeterranean perspective.

BACKGROUND: Med-Index is a one-health front-of-pack (FOP) label, based on Mediterranean diet (MedDiet) principles, developed to summarize information about the nutritional properties and related-health benefits of any food as well as its sustainable production processes, and the associated food company's social responsibility parameters in a new "Planeterranean" perspective. Thus, Med-Index can be adopted in and by any European region and authority as well as worldwide; this is achieved by consumption and cooking of locally available and sourced foods that respect MedDiet principles, both in terms of healthy nutrition and sustainable production. The huge body of scientific evidence about the health benefits of the MedDiet model and principles requires a comprehensive framework to encompass the scientific reliability and robustness of this tool. A systematic review was carried out to examine the association between human health and adherence to MedDiet patterns upon which the "Med-Index" tool was subsequently developed. METHODS: MEDLINE and PubMed databases were searched for eligible publications from 1990 to April 2023. Systematic literature reviews, with or without meta-analysis, of clinical trials and observational studies were screened by two independent investigators for eligibility, data extraction, and quality assessment. English language and the time interval 1990-2023 were applied. A registry code CRD42023464807 was generated on PROSPERO and approved for this search protocol. The corrected covered area (CCA), calculated to quantify the degree of overlap between reviews, gave a slight overlap (CCA = 4%). RESULTS: A total of 84 systematic reviews out of 6681 screened records were selected. Eligible reviews included studies with predominantly observational designs (61/84, 72.6%%), of which 26/61 referenced studies of mixed observational and RCT designs, while 23/84 (27.4%) were RCT-only systematic reviews. Seventy-nine different entries were identified for health outcomes, clustered into 10 macro-categories, each reporting a statistically significant association with exposure to the MedDiet. Adherence to MedDiet was found to strongly benefit age-related chronic diseases (21.5%), neurological disorders (19%), and obesity-related metabolic features (12.65), followed by CVDs (11.4%), cancer (10.1%), diabetes (7.5%), liver health (6.3%), inflammation (5%), mortality (5%), and renal health (1.2%). The quality of the studies was moderate to high. CONCLUSION: In the context of a "Planeterranean" framework and perspective that can be adopted in any European region and worldwide, MedDiet represents a healthy and sustainable lifestyle model, able to prevent several diseases and reduce premature mortality. In addition, the availability of a FOP, such as Med-Index, might foster more conscious food choices among consumers, paying attention both to human and planetary health.

The environment and male reproductive system: the potential role and underlying mechanisms of cadmium in testis cancer.

Cadmium is a known human carcinogen, and has been shown to profoundly affect male reproductive function, at multiple levels, by exerting both endocrine and non-endocrine actions. Nevertheless, the potential role of cadmium in the etiology of testis cancer has been scantly investigated in humans, and, currently, available epidemiological observational studies are insufficient to draw definitive conclusions in this regard. On the contrary, experimental studies in laboratory animals demonstrated that cadmium is a strong inducer of testis tumors, mostly represented by benign Leydig cell adenoma; moreover, malignant transformation was also reported in few animals, following cadmium treatment. Early experimental studies in animals proposed an endocrine-dependent mechanism of cadmium-induced testis tumorigenesis; however, more recent findings from cell-free assays, in vitro studies, and short-term in vivo studies, highlighted that cadmium might also contribute to testis tumor development by early occurring endocrine-independent mechanisms, which include aberrant gene expression within the testis, and genotoxic effects, and take place well before the timing of testis tumorigenesis. These endocrine-independent mechanisms, however, have not been directly investigated on testis tumor samples retrieved from affected, cadmium-treated animals so far. The present review focuses on the relationship between cadmium exposure and testis cancer, by reporting the few epidemiological observational human studies available, and by providing animal-based experimental evidences of cadmium implication in the pathogenesis and progression of testis tumor. Moreover, the relevance of experimental animal studies to human cadmium exposure and the translational potential of experimental findings will be extensively discussed, by critically addressing strengths and weaknesses of available data.

Efficacy and Safety of Lanreotide Autogel and Temozolomide Combination Therapy in Progressive Thoracic Neuroendocrine Tumors (Carcinoid): Results from the Phase 2 ATLANT Study.

INTRODUCTION: Lanreotide autogel (LAN) and temozolomide (TMZ) are guidelines-recommended monotherapies for thoracic neuroendocrine tumors (carcinoids; T-NETs), but prospective data for both combined and monotherapies are lacking. ATLANT (NCT02698410) evaluated efficacy and safety of LAN/TMZ in progressive T-NETs. METHODS: ATLANT was a 12-month, Italian, phase 2, single-arm, open-label, multicenter pilot study. Eligible patients had unresectable, locally advanced/metastatic, well-/moderately differentiated T-NETs with radiological progression. Patients received subcutaneous LAN 120 mg every 28 days and oral TMZ 250 mg/day for 5 consecutive days every 28-day cycle. Main endpoints are disease control rate (DCR) at 9 months (primary; investigator-assessed), median progression-free survival (PFS), biomarkers, and safety. RESULTS: The number of patients was 40; 60% were male. Primary tumor site was lung (90%) and thymus (10%). Carcinoid type was typical (20.0%) and atypical (52.5%). DCR at 9 months was 35.0% (95% confidence interval (CI) 20.63-51.68; nonacceptability threshold ≤10%, p < 0.0001; not significantly above clinically relevant threshold ≥30%, p = 0.2968). DCR between 7.5 and 10.5 months (sensitivity analysis) was 45.0% (95% CI: 29.26-61.51) and clinically relevant (p = 0.0320 at ≥30% threshold). Median PFS was 37.1 (95% CI: 24.1-52.9) weeks. No association was observed between biomarker variations (chromogranin A, neuron-specific enolase, somatostatin receptor type-2, Ki-67, 6-O-methylguanine-DNA-methyl-transferase) and DCR or PFS. Most patients (97.5%) had treatment-emergent adverse events (TEAEs); 72.5% had treatment-related TEAEs. TEAEs were mainly grade 1/2. No unanticipated TEAEs were reported. CONCLUSIONS: This study showed that the LAN/TMZ combination has promising efficacy in progressive T-NETs, and was well tolerated. Larger studies are warranted to support the clinical benefits of LAN/TMZ in patients with T-NETs.