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.

Iron Levels and Markers of Inflammation in a Population of Adults with Severe Obesity, a Cross-Sectional Study.

Low-grade chronic inflammation linked to obesity can lead to alterations in biomarkers of iron status. The aim of this study was to investigate the primary determinant of serum iron levels among anthropometric measurements, body fat, and serum biomarkers of low-grade chronic inflammation in a group of adult individuals with severe obesity. We enrolled 114 individuals (84 females; 30 males) aged 40.96 ± 12.54 years. Weight and body mass index (BMI) were 121.20 ± 22.33 kg and 44.94 ± 7.29 kg/m2, respectively. Some 30% of individuals had class-II obesity (BMI ≥ 35 ≤ 39.9 kg/m2) and 70% had class-III obesity (BMI ≥ 40 kg/m2). A weak, albeit significant, inverse correlation was found between serum iron levels and c-reactive protein (CRP) (r = -0.259, p = 0.008), fibrinogen (r = -0.261, p = 0.006), BMI (r = -0.186, p = 0.04), waist circumference (WC) (r = -0.265, p = 0.004), and fat mass % (r = -0.285, p = 0.003). With multiple linear regression analysis including CRP, fibrinogen, BMI, WC, and fat mass % as independent variables and serum iron levels as dependent variable, WC was entered in the first step (p = 0.001), which was followed by fat mass % (p = 0.047) and CRP (p = 0.047). Grouping the individuals according to the interquartile range of BMI, WC, and fat mass % (Q1-Q4), the lowest serum iron levels were found in Q4 groups of WC and fat mass % (p = 0.02), while no significant differences were found between groups in BMI quartiles. In conclusion, in our study, population serum iron levels were inversely associated with BMI, visceral obesity, fat mass %, CRP, and fibrinogen, but WC was the major negative predictor of serum iron level. These results supported the fact that visceral distribution of body fat, more than obesity per se, was associated with low serum iron levels in adult individuals with severe obesity.

Visceral Obesity and Cytokeratin-18 Antigens as Early Biomarkers of Liver Damage.

Visceral obesity is linked to the progression of fatty liver to nonalcoholic steatohepatitis (NASH). Cytokeratin-18 (CK18) epitopes M30 (CK18M30) and M65 (CK18M65) represent accurate markers for detecting NASH. The aim of this study was to evaluate the association of CK18M30 and CK18M65 levels with anthropometric and metabolic characteristics, liver stiffness, and liver indices of steatosis and fibrosis in a cohort of subjects with visceral obesity; in this cross-sectional study, transient elastography (TE-Fibroscan®), anthropometric measurements, metabolic parameters, High Sensitivity C-Reactive Protein (hsCRP), and CK18M30 and CK18M65 levels (Apoptosense ELISA, PEVIVA, Germany) were evaluated. Fatty Liver Index (FLI), Fibrosis 4 (FIB-4), and Aspartate transaminase (AST)-platelet ratio index (APRI) were calculated; among 48 subjects, 47.2% presented metabolic syndrome, 93.8% hepatic steatosis, 60.4% high liver stiffness, and 14.6% hypertransminasemia, while FIB-4 and APRI were normal. CK18M30 and CK18M65 levels were significantly correlated with waist circumference, AST, ALT, HoMA-IR, liver stiffness, and APRI (p < 0.001). Subjects with CK18 fragments above the median values showed significantly higher waist circumference, HbA1c, AST, ALT, HoMA-IR, FLI, and APRI compared to those with values below the median; CK18M30 and CK18M65 levels correlated well with anthropometric and metabolic characteristics, representing good biomarkers for early identification of NASH in subjects with visceral obesity.

Evening chronotype is associated with hormonal and metabolic disorders in polycystic ovary syndrome.

Despite current treatments for polycystic ovary syndrome (PCOS), a considerable number of women with this syndrome do not reach the treatment goal, suggesting the presence of other probable misdiagnosed features of this syndrome that are not taken into account in the assessment and therefore in the therapeutical approach. The aim of this study was to investigate the prevalence of chronotype categories in women with PCOS and their role in determining hormonal and metabolic aspects of PCOS. This observational case-control study was conducted on 112 women with PCOS and 112 healthy women matched for age and body mass index (BMI). At baseline anthropometric parameters such as weight, height, BMI and waist circumference, clinical parameters such as Ferriman-Gallwey (FG) score, biochemical parameters such as fasting plasma glucose, insulin levels and assessment of the homeostasis model of insulin resistance (HoMA-IR), inflammatory parameters such as C-reactive protein (CRP) and hormonal parameters such as testosterone levels were evaluated. Women with PCOS had a lower chronotype score (p < .001) which indicates a higher prevalence of evening chronotype (EC) category (p = .037) compared to controls. After adjustment for BMI, chronotype score was significantly negatively correlated with CRP levels (r = -0.418, p < .001), testosterone levels (r = -0.543, p < .001) and FG score (r = -0.514, p < .001). Linear regression analysis showed that high testosterone levels were among the factors most associated with a lower chronotype score (p < .001), followed by BMI (p < .001) and HoMA-IR (p < .05). In conclusion, there is a higher prevalence of EC in women with PCOS than in women without the condition, which in turn was associated with a worse hormonal and metabolic profile. These findings provide support for the relevance of including chronotype assessment in the treatment of women with PCOS.

Impact of a Very Low-Calorie Ketogenic Diet (VLCKD) on Changes in Handgrip Strength in Women with Obesity.

The preservation of muscle mass, which is positively associated with muscle strength, has been included among the benefits of ketogenic diets due to the synergistic effects exerted by the reduction in visceral adipose tissue and obesity-related pro-inflammatory status. The handgrip strength (HGS) test is widely used as a single indicator to represent overall muscle strength. The possible association of changes in HGS in patients with obesity during the consumption of a very low-calorie ketogenic diet (VLCKD) has not yet been investigated. The aim of this prospective study was to assess the efficacy of VLCKD on promoting changes in HGS and high-sensitivity C-reactive protein (hs-CRP) levels, as a serological marker of obesity-related, low-grade inflammation, in a population of women with obesity after 45 days of active phase of the VLCKD. This pilot, uncontrolled, single-center, open-label clinical trial examined 247 Caucasian women, aged 18−51 years (body mass index, BMI: 30.0−50.9 kg/m2) who were consecutively enrolled following 45 days of active phase the VLCKD. Anthropometric measures and physical activity were evaluated. Muscle strength was measured by HGS using a grip strength dynamometer. Body composition was evaluated using a bioelectrical impedance analysis (BIA) phase-sensitive system. hs-CRP levels were determined by nephelometric assay. Adherence to the VLCKD, ketosis status, and physical activity were checked weekly by phone call. At day 45, BMI, fat mass (FM), and hs-CRP levels were significantly decreased (∆-7.5 ± 3.1%, ∆-15.6 ± 9.0%, and ∆-39.9 ± 44.6%; respectively; p < 0.001 for all three parameters), while HGS had increased (∆+17.4 ± 13.2%; p < 0.001). After adjusting for ∆BMI, ∆waist circumference, ∆hs-CRP levels, and physical activity, the correlation among changes in ∆HGS (kg), ∆FM (kg), and ∆ fat free mass (FFM) (kg) remained statistically significant (r = −0.331, and r = 0.362, respectively; p < 0.001). Interestingly, the correlation between ∆HGS with ∆FM (r = −0.288, p < 0.001) and ∆FFM (r = 0.395, p < 0.001) were also independent of the percentage of weight loss. We are the first to report that, along with a significant reduction in body weight and an overall improvement in body composition and inflammatory status, the muscle strength evaluated by the HGS test increased in a population of women with obesity after 45 days of the active phase of the VLCKD, also following adjustment for common confounding variables.

Prader-Willi Syndrome in Adults: An Update On Nutritional Treatment and Pharmacological Approach.

PURPOSE OF REVIEW: Prader-Willi syndrome (PWS) is a rare and complex genetic disorder with multiple effects on the metabolic, endocrine, and neurological systems, as well as behavioral and intellectual difficulties. Despite advances in understanding the genetic basis of obesity in PWS, there are conflicting data on its management. Therefore, the present manuscript aims to provide an update on the nutritional treatment and pharmacological approach in adult patients with PWS. RECENT FINDINGS: The management of obesity in patients with PWS is challenging and requires the cooperation of an experienced multidisciplinary team, including the nutritionist. An adequate clinical evaluation including nutritional and biochemical parameters should be performed to tailor the best therapeutic strategy. Both lifestyle and pharmacological interventions may represent useful strategies to prevent the high rate of morbidity and mortality related to PWS. The use of bariatric surgery is still controversial. Although it is imperative to adopt an obesity prevention strategy in childhood, there is promising evidence for the treatment of obesity in adulthood with current obesity medications in conjunction with lifestyle interventions.

Chronotype and Sleep Quality in Obesity: How Do They Change After Menopause?

PURPOSE OF REVIEW: This review primarily provides an overview of the current evidence on chronotype (which reflects an individual's preference for the timing of sleeping, eating, and activity in a 24-h period) and sleep quality changes in obesity in postmenopausal women. It also explores possible nutritional strategies to manage these changes in this phase of a woman's life. RECENT FINDINGS: Menopause is a life stage frequently associated with sleep disturbances and changes in circadian rhythms. Sleep disturbances are one of the main symptoms of menopause and are caused by several factors such as hormonal changes, obesity, and melatonin reduction. In addition, the chronotype also changes following menopause. Nutritional strategies are essential because they could help manage menopausal sleep disturbances and circadian misalignment, particularly by tackling obesity and overweight. In the management of postmenopausal women, especially those experiencing obesity, careful assessment of sleep disturbances and chronotype and subsequent development of the most appropriate treatment, including nutritional management, should be part of the treatment routine.

Adherence to the Mediterranean Diet as a Modifiable Risk Factor for Thyroid Nodular Disease and Thyroid Cancer: Results From a Pilot Study.

Iodine deficiency is the most important established nutritional risk factor for the development of thyroid nodular disease. Nevertheless, to the best of our knowledge, to date no study focused on the association between the adherence to the Mediterranean diet (MD) and thyroid nodular disease. Adherence to the MD was evaluated using the PREvención con DIetaMEDiterránea (PREDIMED) questionnaire. Physical activity, smoking habits, and anthropometric parameters were studied. PREDIMED was used to evaluate the degree of adherence to the MD. Evaluation of fine needle aspiration cytology of thyroid lesions based on 2013 Italian thyroid cytology classification system. Cytology of thyroid nodules was carried out through sonography-guided fine-needle aspiration and patients were divided into 5 categories: TIR2, TIR3a, TIR3b, TIR4, and TIR5. The study population consisted of 794 subjects (554 females, 69.8%), aged 18-65 years, with BMIs ranging from 19.4 to 55.3 kg/m2. Thyroid nodular disease was present in 391 participants (49.2%), and the most frequent cytological categories was TIR2 (18.3 %), followed by a TIR4 (8.9 %). The presence of thyroid nodules was also significantly associated with the lowest adherence to the MD (OR 6.16, p < 0.001). Patients with TIR5 had the lower adherence to the MD (2.15 ± 1.12 score) compared to other TIRs (p < 0.001). The cytological category with high-risk of malignancy (TIR4/TIR5) was significantly associated with the lowest adherence to the MD (OR 137.55, p < 0.001) and PREDIMED score (OR = 0.33, p < 0.001, 95% IC = 0.26-0.41, R 2 = 0.462). At multiple regression analysis, PREDIMED score was the main predictor of both the presence of nodules (p < 0.001) and the cytological category with high-risk of malignancy (p < 0.001). At ROC analysis PREDIMED score ≤ 5 and ≤ 4 (p = 0.001) were the values that predicted the presence of thyroid nodular disease and cytological category with high-risk of malignancy, respectively. In conclusion, our study demonstrated that the low adherence to the MD is associated with the presence of thyroid nodular disease and in particular with those at high-risk of malignancy.

Evening chronotype is associated with severe NAFLD in obesity.

BACKGROUND/OBJECTIVES: Chronotype, i.e., the individual attitude to carry out the daily activities at a certain time of the day, has been reported to play a role in metabolic diseases. Thus, the aim of our study was to investigate the association of non-alcoholic fatty liver disease (NAFLD) with chronotype categories in individuals with obesity. SUBJECTS/METHODS: In this cross-sectional study, participants underwent to anthropometric, biochemical, and the Visceral Adiposity Index (VAI) assessment. Chronotype categories were assessed by the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ). The following indirect indices of NAFLD were calculated: Liver Fat Equation (LFE), Hepatic Steatosis Index (HSI) and Index of Non-alcoholic steatohepatitis (ION). RESULTS: The study population consisted of 87 participants (40.3 ± 12.3 years; BMI 45.6 ± 6.3 kg/m2; 64F/23M). According to the chronotype score, 31.0% were morning (MC), 36.8% were intermediate (IC), and 32.2% evening chronotype (EC). Individuals with IC were significantly younger than those with MC and EC (p = 0.002 and p = 0.047, respectively). EC presented significantly higher BMI (p < 0.001), waist circumference (p = 0.007), and hip circumference (p = 0.001) than MC. Moreover, EC had higher BMI (p < 0.001) and waist circumference (p = 0.011) than IC. All participants presented NAFLD (HSI ≥ 36 and LFE ≥ 5). Nevertheless, only individuals with EC were above the threshold of non-alcoholic steatohepatitis evaluated as ION index (ION ≥ 50). Individuals with EC presented significantly higher VAI (p = 0.036), LFE (p = 0.034), HSI (p < 0.001) and ION (p = 0.014) than MC, also after the adjustment for age, gender, and BMI. CONCLUSION: EC is associated with more severe NAFLD independently of age, gender, and BMI than MC and IC in individuals with obesity.

Mediterranean Diet: What Are the Consequences for Menopause?

Menopause is a natural event occurring in a woman's life that is often accompanied by symptoms that might affect the quality of life. Diet has been shown to influence menopausal-related symptoms. Therefore, the present study aimed to investigate whether the adherence to the Mediterranean Diet (MD) might influence menopausal symptoms in women with obesity. This cross-sectional study involved postmenopausal women with obesity. Anthropometric and clinical parameters, and lifestyle habits were evaluated. All participants underwent interview questionnaires to assess: the adherence to the MD (PREDI PREvencion con DIetaMEDiterranea, PREDIMED), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and severity of menopausal symptoms (Menopausal Rating Scale, MRS). One hundred postmenopausal women were enrolled (age 57.1 ± 7.3 years, BMI 35.0 ± 5.5 kg/m2). The mean PREDIMED score was 7.82 ± 1.66 showing moderate adherence to MD. Women in the marked MRS class had a significantly lower PREDIMED score than the none-to-moderate MRS class (p=0.036). The intake of legumes was associated with a lower MRS class (r= -0.201, p=0.045). In addition, the intake of extra-virgin olive oil inversely correlated with psychological symptoms (r= -0.230 p=0.021). Finally, 79% of participants were poor sleepers (mean PSQI score was 8.68 ± 3.6) and women in the severe MRS class had a worse sleep quality compared to other MRS classes. Post-menopausal women with marked menopausal symptoms had low adherence to MD. Legume consumption was associated with lower menopausal symptoms severity while extra virgin olive oil consumption was associated with lower psychological symptoms.

Phase angle as an easy diagnostic tool for the nutritionist in the evaluation of inflammatory changes during the active stage of a very low-calorie ketogenic diet.

BACKGROUND AND AIMS: Very low-calorie ketogenic diets (VLCKDs) have recently gained increasing interest for their anti-inflammatory effects. Phase angle (PhA), a bioelectrical impedance analysis (BIA)-derived measure used as a screening tool to assess inflammatory status in various clinical conditions has recently been suggested as a novel predictor of inflammatory status in correlation with high-sensitivity C-reactive protein (hs-CRP) levels. PhA's usefulness in monitoring inflammatory status changes in patients with obesity during active phase VLCKD has not yet been explored. The aim of this pilot study was to examine the role of PhA as a biomarker detecting early inflammatory status changes in women with overweight and obesity 1 month into the active stage of a VLCKD. METHODS-RESULTS: This uncontrolled, single-center, open-label pilot clinical study investigated 260 consecutively enrolled Caucasian women aged 18-69 years (BMI 25.0-50.9 kg/m2) after 31 days of an active stage VLCKD. Anthropometric measurements and PhA were assessed. hs-CRP levels were determined by nephelometric assay. Dietary compliance, physical activity recommendations, and ketosis status were tested weekly by telephone recall. At Day 31, BMI, WC, and hs-CRP levels were observed to have decreased (∆-7.3 ± 2.9%, ∆-6.3 ± 5.0%, and ∆-38.9 ± 45.6%; respectively), while PhA had increased (∆+8.6 ± 12.5%). Changes in ∆ hs-CRP were significantly correlated with changes in BMI, WC, and PhA (p < 0.001). After adjusting for confounding variables, the correlation between changes in ∆ PhA and ∆ hs-CRP remained statistically significant, albeit attenuated (p = 0.024). CONCLUSION: This is the first study reporting how, along with the expected rapid effect on body weight, PhA changes during active stage VLKCD occurred very early on and independently of weight loss, and were negatively associated with hs-CRP levels. These findings further support the VLCKD as a first-line dietary intervention to obtain a rapid effect on the obesity-related inflammatory status. They also suggest the possible role of PhA as an easy diagnostic tool to detect inflammation, thereby avoiding blood sampling and expensive biochemical assays. It is also posited that changes in PhA could help nutritionists correctly plan the different stages of the VLCKD protocol.

Dietary Recommendations for Post-COVID-19 Syndrome.

At the beginning of the coronavirus disease (COVID-19) pandemic, global efforts focused on containing the spread of the virus and avoiding contagion. Currently, it is evident that health professionals should deal with the overall health status of COVID-19 survivors. Indeed, novel findings have identified post-COVID-19 syndrome, which is characterized by malnutrition, loss of fat-free mass, and low-grade inflammation. In addition, the recovery might be complicated by persistent functional impairment (i.e., fatigue and muscle weakness, dysphagia, appetite loss, and taste/smell alterations) as well as psychological distress. Therefore, the appropriate evaluation of nutritional status (assessment of dietary intake, anthropometrics, and body composition) is one of the pillars in the management of these patients. On the other hand, personalized dietary recommendations represent the best strategy to ensure recovery. Therefore, this review aimed to collect available evidence on the role of nutrients and their supplementation in post-COVID-19 syndrome to provide a practical guideline to nutritionists to tailor dietary interventions for patients recovering from COVID-19 infections.

Metabolically Healthy Obesity (MHO) vs. Metabolically Unhealthy Obesity (MUO) Phenotypes in PCOS: Association with Endocrine-Metabolic Profile, Adherence to the Mediterranean Diet, and Body Composition.

Obesity and obesity-related low-grade inflammation are common findings in polycystic ovary syndrome (PCOS), the most common endocrine-metabolic disorder-affecting women in reproductive age. The terms metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) have been introduced to define individuals with obesity in whom cardio-metabolic risk factors are absent or present, respectively. To date, evidence investigating differences in body composition and adherence to the Mediterranean diet (MD) between MHO and MUO-PCOS women are lacking. Aim of this study was to better characterize the determinants of the metabolic health status in PCOS patients with obesity according to MHO and MUO phenotypes by evaluating endocrine-metabolic profile, inflammatory status, adherence to the MD, and body composition. The study population consisted of 94 treatment-naïve women with PCOS and obesity (BMI = 38.23 ± 6.62 kg/m2 and age = 24.12 ± 3.68 years). Compared PCOS MHO with PCOS MUO patients, the latter had higher levels of high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), testosterone (p < 0.001), and insulin (p < 0.001), worse metabolic parameters, and higher Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI), and Fatty liver Index (FLI) (p < 0.001). Furthermore, PCOS MUO patients had lower adherence to the MD (p < 0.001) in spite of the same total energy intake (p = 0.102) as compared to PCOS MHO. The presence of MUO was associated with highest hs-CRP levels (OR = 1.49, p < 0.001), more severe hyperandrogenism and cardio-metabolic indices (p < 0.001). On the contrary, being PCOS MUO was associated with lower adherence to the MD (OR = 0.28, p < 0.001), and smaller PhAs (OR = 0.04, p < 0.001). Using a regression linear analysis model PREDIMED score entered at the first step (p < 0.001), followed by VAI (p < 0.001), and FLI (p = 0.032) in this analysis. At ROC analysis, a PREDIMED score of ≤4 (p < 0.001, AUC 0.926) could serve as a threshold for a significantly increased risk of presence the MUO-PCOS phenotype. To the best of our knowledge, this is the first study that characterized MHO and MUO-PCOS women on the basis of their adherence to the MD, body composition, and cardio-metabolic indices, providing evidence of the usefulness of adjunctive diagnostic parameters to better differentiate the MHO/MHO phenotypes in this cohort of PCOS patients with obesity.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile.

AIM: To investigate the potential association among Craniopharyngioma (CP), chronotypes and metabolic risk profile. SUBJECTS AND METHODS: The study population included 28 patients (46.4% males; 42.6 ± 15.8 years) and 28 controls, age, gender and BMI matched (46.4% males; 46.5 ± 12.9 years). In this study sample, we evaluated: anthropometric measurements (waist circumference, WC; BMI), plasma glucose, lipid profile, and systolic (SBP) and diastolic (DBP) blood pressure. Morningness-Eveningness was measured with the Horne-Ostberg Morningness-Eveningness Questionnaire (MEQ), which included 19 questions about preferred sleep time and daily performance. RESULTS: in both patients and controls grade I obesity was detected in 15 subjects (53.6%), grade II obesity in 13 subjects (46.4%). In the patient group, the mean score of chronotype was 47.8 ± 12.6. In particular, 9 patients (32.1%) exhibited the morning chronotype, 6 (21.4%) the intermediate chronotype and 13 (46.4.%) the evening chronotype. No significant difference was found in gender and age among the chronotype categories. Patients with the evening chronotype had higher blood pressure values and worse metabolic parameters than those with the morning chronotype. In the control group, the mean score of the chronotype was 57.6 ± 9.5. In particular, 16 (57.1%) subjects exhibited the morning chronotype, 10 (35.7%) the intermediate chronotype and only 2 (7.1.%) the evening chronotype. The prevalence of intermediate and evening chronotypes was higher in females than males (p = 0.021), while males have a higher prevalence of the morning chronotype. Subjects with intermediate and evening chronotypes had worse metabolic parameters than those with the morning chronotype. In patients, the chronotype score was inversely correlated to WC, BMI, SBP, DBP, plasma glucose, total cholesterol, triglycerides, LDL cholesterol and positively correlated with HDL cholesterol. No correlation was found between age and chronotype. In controls, the chronotype score was inversely correlated to WC, BMI, plasma glucose, total cholesterol, LDL cholesterol. No correlation was found among chronotype and age, blood pressure, triglycerides, HDL cholesterol. Considering the whole population of the study (patients and controls), at logistic regression the chronotype score was significantly associated with the presence of CP. CONCLUSIONS: for the first time thus far, our study puts the light on the association of the CP with chronotypes and metabolic alterations in this disease, which are the main determinants of the reduced quality of life, higher morbidity and mortality in this setting of patients. This finding suggests that alterations of chronotype might represent an adjunctive risk for CP patients and a possible target for their integrate management.

Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa).

In this case-control, cross-sectional, observational study, we evaluated circulating trimethylamine n-oxide (TMAO) levels, a gut-derived metabolite associated with inflammation and cardiometabolic risk, in patients with hidradenitis suppurativa (HS), a highly disabling inflammatory skin disease associated with an elevated prevalence of comorbidities, especially cardiovascular and metabolic diseases. In this study, we enrolled 35 naive-treatment patients with HS and 35 controls, matched for sex, age, and body mass index (BMI). HS Sartorius score was 49.0 (33.0-75.0), while according to the Harley system 12 and 23 patients presented grade 1 and grade 2 severity, respectively. HS patients had a lower adherence to the Mediterranean diet (MD) (p = 0.002), lower phase angle (PhA) (p < 0.001), and higher circulating TMAO levels (p < 0.001) than the control group. HS patients with grade 2 rather than grade 1 of Harley grade severity showed a higher BMI (p = 0.007), waist circumference (p = 0.016), total energy intake (p = 0.005), and lower PhA (p < 0.001) and adherence to the MD (p = 0.003). Of interest, patients with Hurley grade 2 of severity exhibited higher circulating TMAO levels (p < 0.001) compared to grade 1. Circulating TMAO levels showed a positive correlation with HS Sartorius score even after adjustment for confounding covariates, including BMI, waist circumference, adherence to the MD, total energy intake, and PhA (r = 0.570, p = 0.001). Using a linear regression model, circulating TMAO levels and PhA were the main predictors of the clinical severity of HS.

Phase Angle as an Easy Diagnostic Tool of Meta-Inflammation for the Nutritionist.

Phase angle (PhA), a noninvasive bioimpedance marker, is a useful tool for nutritional screening in several diseases. C-reactive protein (CRP), a strong risk factor for metabolic and cardiovascular diseases, is a commonly used biomarker of meta-inflammation. As both PhA and CRP are influenced by age, BMI, and nutritional status, and exhibit a clear sex dimorphism, we examined the association between PhA and CRP levels in 1855 subjects (680 males and 1175 females), aged 18-59 years, with BMIs ranging from 19.5 to 69.4 kg/m2, stratified according to sex. PhA values and CRP levels were significantly lower in females than males (p < 0.001), while the adherence to the Mediterranean diet (MD) was lower in males compared to females (p < 0.001). After adjusting for age, physical activity, BMI, waist circumference, and adherence to the MD, PhA remained negatively associated with CRP levels in both genders (p < 0.001). In the ROC analysis, PhA ≤ 5.5° in males and ≤5.4° in females were the threshold values predicting increased hs-CRP levels. These results suggested that PhA might represent a valid predictor of CRP levels in both sexes regardless of body weight and adherence to the MD, which avoids the collection of blood sampling and expensive biochemical assays.

Impact of Long-Term Growth Hormone Replacement Therapy on Metabolic and Cardiovascular Parameters in Adult Growth Hormone Deficiency: Comparison Between Adult and Elderly Patients.

Growth hormone deficiency (GHD) in adults is due to a reduced growth hormone (GH) secretion by the anterior pituitary gland which leads to a well-known syndrome characterized by decreased cognitive function and quality of life (QoL), decreased bone mineral density (BMD), increased central adiposity with a reduction in lean body mass, decreased exercise tolerance, hyperlipidemia and increased predisposition to atherogenesis. Considering some similar features between aging and GHD, it was thought that the relative GH insufficiency of the elderly person could make an important contribution to the fragility of elderly. GH stimulation tests are able to differentiate GHD in elderly patients (EGHD) from the physiological reduction of GH secretion that occurs with aging. Although there is no evidence that rhGH replacement therapy increases the risk of developing Diabetes Mellitus (DM), reducing insulin sensitivity and inducing cardiac hypertrophy, long-term monitoring is, however, also mandatory in terms of glucose metabolism and cardiovascular measurements. In our experience comparing the impact of seven years of rhGH treatment on metabolic and cardiovascular parameters in GHD patients divided in two groups [adult (AGHD) and elderly (EGHD) GHD patients], effects on body composition are evident especially in AGHD, but not in EGHD patients. The improvements in lipid profile were sustained in all groups of patients, and they had a lower prevalence of dyslipidemia than the general population. The effects on glucose metabolism were conflicting, but approximately unchanged. The risk of DM type 2 is, however, probably increased in obese GHD adults with impaired glucose homeostasis at baseline, but the prevalence of DM in GHD is like that of the general population. The increases in glucose levels, BMI, and SBP in GHD negatively affected the prevalence of Metabolic Syndrome (MS) in the long term, especially in AGHD patients. Our results are in accordance to other long-term studies in which the effects on body composition and lipid profile are prominent.

Papillary thyroid carcinoma arising in ectopic thyroid tissue within sternocleidomastoid muscle: a review of current literature.

The prevalence of ectopic thyroid tissue as consequence of an aberrant migration of thyroid during embryogenesis ranges up to 10% in autopsy studies. The differential diagnosis between the relatively rare occurrence of a primary carcinoma arising in ectopic thyroid tissue and the more frequent presence of cervical lymph node metastasis from papillary thyroid carcinoma (PTC) might represent a difficult challenge in the clinical practice. The clinical relevance of these lesions lies in their risk of hidden primary thyroid cancer. Our intention is to provide in this review the current limited data available and to report an unusual localization of primary PTC arising from an extra-thyroid area, responsible for a solitary cervical mass as initial manifestation. The tumor developed in an ectopic thyroid tissue embedded within the clavicular head of the sternocleidomastoid muscle and was completely separated from the thyroid. Surgical excision of ectopic thyroid tissue with clavicular head of sternocleidomastoid muscle along with total thyroidectomy and central and selective lateral neck dissection were carried out. Histopathology was diagnostic for ectopic PTC and no primary lesions in the thyroid gland neither metastatic lymph nodes were found. Tumor cells were positive for thyroid transcription factor-1and thyroglobulin, and negative for CD56. A postoperative adjuvant radioiodine ablation was given after recombinant human thyroid-stimulating hormone (TSH) stimulation and the post-treatment whole body scan was negative. After the evaluation at six months showing negative neck ultrasound and undetectable thyroglobulin levels, while TSH suppressed and after recombinant human TSH stimulation, the patient was re-evaluated every six months. At two years, the patient remained completely free of disease and is currently on substitutive dose of l-thyroxine. Endocrinologists and neck surgeons must be aware of the rare possibility of primary PTC arising from ectopic thyroid tissue within the sternocleidomastoid muscle.

Phase Angle: Could Be an Easy Tool to Detect Low-Grade Systemic Inflammation in Adults Affected by Prader-Willi Syndrome?

Prader-Willi syndrome (PWS) is the most common genetic inherited obesity syndrome. Obesity-related complications, mostly related to chronic low-grade systemic inflammation (LGI), are the commonest cause of mortality and morbidity in PWS adults. Phase angle (PhA) is an easy tool to screen a state of LGI in healthy subjects and in subjects with obesity and is obtained from bioelectrical impedance analysis (BIA). The aim of this study was to validate the PhA in PWS adults as a potential biomarker of LGI. In this single-center, cross-sectional study, fifteen PWS adults (six males, aged 19-41 years, and body mass index (BMI) 31.0-68.0 Kg/m2) and fifteen control subjects matched by gender, age, and BMI were evaluated. PhA values were significantly lower (p < 0.001), while high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher (p < 0.001) in PWS adults compared with controls (p < 0.001), without a gender difference in the latter. After adjustment for gender, BMI, and waist circumference, significant correlation was found between PhA and hs-CRP levels (r = -0.69, p = 0.01). At the ROC analysis, the threshold value of PhA predicting the highest hs-CRP levels above the median value was found at PhA ≤ 4.8° (p = 0.01; AUC, 0.82; standard error, 0.12; 95% CI, 0.58 to 1.00). These results suggest that PWS adults had a significant higher degree of LGI compared with their counterparts. Moreover, our finding suggest that PhA is a valid biomarker of LGI also in PWS adults.

Influence of the Mediterranean Diet on 25- Hydroxyvitamin D Levels in Adults.

The Mediterranean diet (MD) is a dietary pattern effective in terms of prevention of obesity-related diseases, and represents the gold standard in preventive medicine, due to the synergistic action of many nutrients with antioxidant and anti-inflammatory properties. In addition, excess body weight significantly increases the risk of hypovitaminosis D, a well-recognized common feature of individuals with obesity. It is well-known that there is a clear gender difference in the adherence to the MD. The aim of this study was to investigate the association between adherence to the MD and 25-hydroxyvitamin D (25OHD) levels in adults, according to gender. Study population consisted of 617 participants; 296 were males and 321 were females, matched by age and body mass index (BMI). A validated 14-item questionnaire PREDIMED (Prevención con dieta Mediterránea) was used for the assessment of adherence to the MD. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Females have a higher PREDIMED score than males (7.4 ± 2.8 vs. 6.7 ± 3.1 score, p = 0.001), and according to PREDIMED categories, a greater percentage of males had low adherence to the MD compared to their female counterparts (40.2% vs. 37.1%; χ2 = 8.94, p = 0.003). The 25OHD levels were higher in males than in females (18.3 ± 7.3 vs. 16.8 ± 7.8 ng/mL, p = 0.01), and a higher percentage of males had sufficient 25OHD levels (>30 ng/mL) than their female counterparts (10.5% vs. 3.4%, χ2 = 10.96, p < 0.001). Stratifying the sample population according to 25OHD categories, BMI decreased and PREDIMED score increased significantly along with the increased 25OHD levels, in both males and females, respectively (p < 0.001). Looking at the bivariate correlations, PREDIMED score was positively correlated with 25OHD levels after adjusting for age and BMI, in both males (r = 0.21, p < 0.001) and females (r = 0.30, p < 0.001). At the bivariate proportional odds ratio (OR) model, 25OHD levels presented the highest OR values in the category low adherence vs. high adherence to the MD, in both genders (OR 1.21 and OR 1.31, in males and females, respectively). Receiver operator characteristic (ROC) analysis was performed to determine the cut-off values of PREDIMED scores predictive of 25OHD levels: PREDIMED score >5 in males (p < 0.001) and >7 in females (p < 0.001) could serve as thresholds for 25OHD levels above the median. The results of our study highlighted a novel positive association between adherence to the MD and 25OHD levels in both genders. Although 25OHD levels were higher in males than females, 69.7% were deficient. To the best of our knowledge, this is the first study to show that high adherence to the MD is associated with low BMI and high 25OHD levels in both genders, probably through the anti-inflammatory and anti-oxidant effects that are synergistically exerted by either MD or vitamin D on body weight.