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.

Recent advances and future challenges in the diagnosis of neuroendocrine neoplasms.

Neuroendocrine neoplasms (NEN) are a heterogeneous group of malignancies with increasing incidence, whose diagnosis is usually delayed, negatively impacting on patients' prognosis. The latest advances in pathological classifications, biomarker identification and imaging techniques may provide early detection, leading to personalized treatment strategies. In this narrative review the recent developments in diagnosis of NEN are discussed including progresses in pathological classifications, biomarker and imaging. Furthermore, the challenges that lie ahead are investigated. By discussing the limitations of current approaches and addressing potential roadblocks, we hope to guide future research directions in this field. This article is proposed as a valuable resource for clinicians and researchers involved in the management of NEN. Update of pathological classifications and the availability of standardized templates in pathology and radiology represent a substantially improvement in diagnosis and communication among clinicians. Additional immunohistochemistry markers may now enrich pathological classifications, as well as miRNA profiling. New and multi-analytical circulating biomarkers, as liquid biopsy and NETest, are being proposed for diagnosis but their validation and availability should be improved. Radiological imaging strives for precise, non-invasive and less harmful technique to improve safety and quality of life in NEN patient. Nuclear medicine may benefit of somatostatin receptors' antagonists and membrane receptor analogues. Diagnosis in NEN still represents a challenge due to their complex biology and variable presentation. Further advancements are necessary to obtain early and minimally invasive diagnosis to improve patients' outcomes.

Harnessing the Synergy of SGLT2 Inhibitors and Continuous Ketone Monitoring (CKM) in Managing Heart Failure among Patients with Type 1 Diabetes.

Heart failure (HF) management in type 1 diabetes (T1D) is particularly challenging due to its increased prevalence and the associated risks of hospitalization and mortality, driven by diabetic cardiomyopathy. Sodium-glucose cotransporter-2 inhibitors (SGLT2-is) offer a promising avenue for treating HF, specifically the preserved ejection fraction variant most common in T1D, but their utility is hampered by the risk of euglycemic diabetic ketoacidosis (DKA). This review investigates the potential of SGLT2-is in T1D HF management alongside emergent Continuous Ketone Monitoring (CKM) technology as a means to mitigate DKA risk through a comprehensive analysis of clinical trials, observational studies, and reviews. The evidence suggests that SGLT2-is significantly reduce HF hospitalization and enhance cardiovascular outcomes. However, their application in T1D patients remains limited due to DKA concerns. CKM technology emerges as a crucial tool in this context, offering real-time monitoring of ketone levels, which enables the safe incorporation of SGLT2-is into treatment regimes by allowing for early detection and intervention in the development of ketosis. The synergy between SGLT2-is and CKM has the potential to revolutionize HF treatment in T1D, promising improved patient safety, quality of life, and reduced HF-related morbidity and mortality. Future research should aim to employ clinical trials directly assessing this integrated approach, potentially guiding new management protocols for HF in T1D.

Investigational drugs for the Treatment of Acromegaly: new agents to transform therapy.

INTRODUCTION: Disease control is essential to decrease morbidity burden and mortality in acromegaly patients. In the last decades, the availability of new drugs increased the rate of disease control. However, up to 55% of patients remain uncontrolled despite available treatment strategies in real-world data. The reasons for this finding may include poor adherence, inadequate tolerability, therapeutic inertia, and high costs. Since acromegaly is a chronic disease and medical therapy is usually life-long, patient's adherence to treatment is fundamental in both achieving and maintaining disease control. Less invasive routes of administration could improve adherence and concur to increase disease control rate. AREAS COVERED: The aim of current review is to provide a detailed update about investigational drugs for acromegaly treatment currently under investigation as paltusotine, ONO-5788, AP102, GT-02037, ISIS 766,720, CAM2024, Lanreotide PRF, DP1038, MTD201, solid dose injection of octreotide. EXPERT OPINION: Medical therapy of acromegaly is an evolving field. Current studies are addressing patient's needing for both new molecules and less invasive routes of administration for already existing drugs. It cannot be ruled out that drugs currently used for other disease such as cancers could be considered in the future for the treatment of acromegaly.

Dyslipidemia, lipid-lowering agents and neuroendocrine neoplasms: new horizons.

PURPOSE: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies originating from cells with a neuroendocrine phenotype. The complex relationship between lipid metabolism and cancer is gaining interest and a potential anti-cancer effect of lipid lowering agents is being considered. This review aims to discuss the current understanding and treatment of dyslipidaemia in NENs, focusing on the role of lipid lowering agents, including new therapeutic approaches, and future perspectives as possible tool in cancer prevention and tumor-growth control. METHODS: We performed an electronic-based search using PubMed updated until December 2023, summarizing the available evidence both in basic and clinical research about lipid lowering agents in NENs. RESULTS: Dyslipidemia is an important aspect to be considered in NENs management, although randomized studies specifically addressing this topic are lacking, unlike other cancer types. Available data mainly regard statins, and in vitro studies have demonstrated direct antitumor effects, including antiproliferative effects in some cancers, supporting possible pleiotropic effects also in NENs, but data remain conflicting. Ezetimibe, omega 3-fatty acids, fibrates and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may enhance the regulation of lipid homeostasis, as demonstrated in other cancers. CONCLUSIONS: Targeting dyslipidemia in NENs should be part of the multidisciplinary management and an integrated approach may be the best option for both metabolic and tumor control. Whether lipid lowering agents may directly contribute to tumor control remains to be confirmed with specific studies, focusing on association with other metabolic risk, disease stage and primary site.

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.

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.

Sharing the multidisciplinary clinical approach to peri- and postmenopausal women: A Delphi consensus among Italian gynecologists, endocrinologists, and cardiologists for an integrated and optimal approach to clinical practice.

OBJECTIVE: The critical phase of perimenopausal period is marked by a reduction in estrogen levels, leading to various clinical issues (vasomotor and neurodegenerative symptoms, increased osteoporosis risk and cardiovascular risk). These complex clinical scenarios pose challenges to clinicians in providing the right support for diagnosis and treatment. A group of Italian cardiologists, endocrinologists, and gynecologists conducted a survey among expert colleagues to assess consensus on controversial issues and best practices for screening and treating peri- and postmenopausal women. METHODS: The Delphi methodology was used to analyze responses from a qualitative expert panel comprising 25 cardiologists, 25 endocrinologists, and 25 gynecologists, selected nationwide. Two consecutive questionnaires were proposed between February and May 2023. Agreement among experts was assessed following the Delphi method as developed by the RAND Corporation. RESULTS: The results of this Delphi Consensus have been shared by the leading scientific societies: Italian Society of Cardiology, Italian Society of Endocrinology, Italian Society of Gynecology and Obstetrics, and Italian Hospital Obstetricians Gynecologists Association. CONCLUSIONS: The experts highlighted comorbidities and hormone deprivation as crucial clinical problems to be evaluated in perimenopausal women, requiring investigation from cardiovascular and endocrinologic perspectives to assess cardiovascular risk, involving the use of BMI, standard blood samples, endocrine-metabolic tests, and lifestyle assessment, particularly in women with higher cardiovascular and metabolic risks candidates for hormone replacement therapy (HRT). The experts also agreed on the benefits of HRT in improving lipid metabolism and reducing insulin resistance, thereby mitigating the metabolic risks associated with menopause. However, this therapy should be tailored considering individual women's comorbidities and thrombotic risk.

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.

Nutritional interventions in prison settings: a scoping review.

BACKGROUND: Mounting evidence has shown that incarceration can affect the health and well-being of individuals and increase the risk of noncommunicable diseases (NCDs). Diet quality is known to be one of the main determinants of risk of NCDs, and dietary changes are the first approach used in primary care to reduce the incidence of NCDs. OBJECTIVE: This scoping review aimed to summarize the evidence for (1) the diet quality of inmates, and (2) the effect of nutritional intervention in prison systems. In addition, we aimed to describe limitations in the current literature and to suggest potential future research areas. METHOD: A systematic search was performed in 2 databases (PubMed and Web of Science) using predefined search terms and covering the period May 2023 to June 2023. Additionally, reference lists from the retrieved studies were hand-searched to identify any additional relevant publications. The identified literature was screened based on defined search strategies, criteria, and research questions defined using the PICo (population or problem, interest, and context) framework. The review was conducted referring to the PRISMA-ScR and the PICo framework. RESULTS: A total of 19 studies out of 63 initially identified records were included in this review (11 cross-sectional evaluations and 9 intervention-based studies). In almost all studies, assessment of the diet quality of menus showed the menus to be nutritionally adequate, except for having a higher-than-recommended intake of total energy, saturated fatty acids, sodium, cholesterol, and sugar. In addition, some studies reported a lower-than-recommended intake of fiber, magnesium, potassium, vitamins D, E, and A, and omega-3 fatty acids. Nutritional interventions were mainly planned in the form of workshops, seminars, and written material to deliver information on healthy dietary choices. Although no significant changes in inmates' dietary choices were observed in any of the studies, a high participation rate was detected. CONCLUSION: Inmates might require additional prevention intervention to reduce their susceptibility to cardiometabolic diseases by virtue of their isolation from community facilities. Interventions should be tailored to the characteristics of prison settings and inmates to increase adherence to nutritional recommendations.

Exploring the Impact of Glycemic Control on Diabetic Retinopathy: Emerging Models and Prognostic Implications.

This review addresses the complexities of type 1 diabetes (T1D) and its associated complications, with a particular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of this review is devoted to technological advances in diabetes management, particularly the use of hybrid closed-loop systems (HCLSs) and to the potential of open-source HCLSs, which could be easily adapted to different patients' needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient 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 trans differentiation. 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.

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.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083).

Factors associated with disease control failure in acromegaly patients treated with pegvisomant: an ACROSTUDY analysis.

Purpose: The aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally. Methods: We analyzed data from ACROSTUDY, an open-label, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed-effects logistic regression models, taking into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% CI. Results: Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1 <300 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-500 µg/L (ES = 0.37, 95% CI: 0.32-0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53-0.64). Conclusion: Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI and pegvisomant dose as predictors of long-term control of acromegaly. Significance statement: Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.

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.

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.

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.

Current understanding of pathogenetic mechanisms in neuroendocrine neoplasms.

INTRODUCTION: Despite the fact that important advances in research on neuroendocrine neoplasms (NENs) have been made, consistent data about their pathogenetic mechanism are still lacking. Furthermore, different primary sites may recognize different pathogenetic mechanisms. AREAS COVERED: This review analyzes the possible biological and molecular mechanisms that may lead to NEN onset and progression in different organs. Through extensive research of the literature, risk factors including hypercholesterolemia, inflammatory bowel disease, chronic atrophic gastritis are evaluated as potential pathogenetic mechanisms. Consistent evidence is available regarding sporadic gastric NENs and MEN1 related duodenopancreatic NENs precursor lesions, and genetic-epigenetic mutations may play a pivotal role in tumor development and bone metastases onset. In lung neuroendocrine tumors (NETs), diffuse proliferation of neuroendocrine cells on the bronchial wall (DIPNECH) has been proposed as a premalignant lesion, while in lung neuroendocrine carcinoma nicotine and smoke could be responsible for carcinogenic processes. Also, rare primary NENs such as thymic (T-NENs) and Merkel cell carcinoma (MCC) have been analyzed, finding different possible pathogenetic mechanisms. EXPERT OPINION: New technologies in genomics and epigenomics are bringing new light to the pathogenetic landscape of NENs, but further studies are needed to improve both prevention and treatment in these heterogeneous neoplasms.

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.