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

Trimethylamine-N-oxide (TMAO) as novel potential biomarker of early predictors of metabolic syndrome

There is a mechanistic link between the gut-derived metabolite trimethylamine-N-oxide (TMAO) and obesity-related diseases, suggesting that the TMAO pathway may also be linked to the pathogenesis of obesity. The Visceral Adiposity Index (VAI), a gender-specific indicator of adipose dysfunction, and the Fatty Liver Index (FLI), a predictor of non-alcoholic fatty liver disease (NAFLD), are early predictors of metabolic syndrome (MetS). In this cross-sectional observational study, we investigated TMAO levels in adults stratified according to Body Mass Index (BMI) and the association of TMAO with VAI and FLI. One hundred and thirty-seven adult subjects (59 males; 21⁻56 years) were enrolled. TMAO levels were detected using HPLC/MS analysis. Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), VAI and FLI were included as cardio-metabolic indices. TMAO levels increased along with BMI and were positively associated with VAI and FLI, independently, on common potential covariates. The most sensitive and specific cut-offs for circulating levels of TMAO to predict the presence of NAFLD-FLI and MetS were ≥8.02 µM and ≥8.74 µM, respectively. These findings allow us to hypothesize a role of TMAO as an early biomarker of adipose dysfunction and NAFLD-FLI in all borderline conditions in which overt MetS is not present, and suggest that a specific cut-off of TMAO might help in identifying subjects at high risk of NAFLD

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

Prader&ndash;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&ndash;41 years, and body mass index (BMI) 31.0&ndash;68.0 Kg/m2) and fifteen control subjects matched by gender, age, and BMI were evaluated. PhA values were significantly lower (p &lt; 0.001), while high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher (p &lt; 0.001) in PWS adults compared with controls (p &lt; 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 = &minus;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 &le; 4.8&deg; (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

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 &lt; 0.001), testosterone (p &lt; 0.001), and insulin (p &lt; 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 &lt; 0.001). Furthermore, PCOS MUO patients had lower adherence to the MD (p &lt; 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 &lt; 0.001), more severe hyperandrogenism and cardio-metabolic indices (p &lt; 0.001). On the contrary, being PCOS MUO was associated with lower adherence to the MD (OR = 0.28, p &lt; 0.001), and smaller PhAs (OR = 0.04, p &lt; 0.001). Using a regression linear analysis model PREDIMED score entered at the first step (p &lt; 0.001), followed by VAI (p &lt; 0.001), and FLI (p = 0.032) in this analysis. At ROC analysis, a PREDIMED score of ≤4 (p &lt; 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

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 (Prevenci&oacute;n con dieta Mediterr&aacute;nea) 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 &plusmn; 2.8 vs. 6.7 &plusmn; 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%; &chi;2 = 8.94, p = 0.003). The 25OHD levels were higher in males than in females (18.3 &plusmn; 7.3 vs. 16.8 &plusmn; 7.8 ng/mL, p = 0.01), and a higher percentage of males had sufficient 25OHD levels (&gt;30 ng/mL) than their female counterparts (10.5% vs. 3.4%, &chi;2 = 10.96, p &lt; 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 &lt; 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 &lt; 0.001) and females (r = 0.30, p &lt; 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 &gt;5 in males (p &lt; 0.001) and &gt;7 in females (p &lt; 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

Thyroid papillary carcinoma arising in ectopic thyroid tissue within sternocleidomastoid muscle: case report and 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 review the current limited data available and to report an unusual localization of primary PTC arising from an extrathyroid 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 131I 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 lthyroxine. Endocrinologists and neck surgeons must be aware of the rare possibility of primary PTC arising from ectopic thyroid tissue within the sternocleidomastoid muscle

The Sun’s Vitamin in Adult Patients Affected by Prader–Willi Syndrome

Prader&ndash;Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia with progressive, severe obesity, and an increased risk of obesity-related comorbidities in adult life. Although low dietary vitamin D intake and low 25-hydroxy vitamin D (25OHD) levels are commonly reported in PWS in the context of bone metabolism, the association of low 25OHD levels with fat mass has not been extensively evaluated in PWS adults. The aims of this study were to investigate the following in PWS adults: (1) 25OHD levels and the dietary vitamin D intake; (2) associations among 25OHD levels with anthropometric measurements and fat mass; (3) specific cut-off values for body mass index (BMI) and fat mass predictive of the 25OHD levels. In this cross-sectional, single-center study we enrolled 30 participants, 15 PWS adults (age 19&ndash;41 years and 40% males) and 15 control subjects matched by age, sex, and BMI from the same geographical area (latitude 40&deg; 49&rsquo; N; elevation 17 m). Fat mass was assessed using a bioelectrical impedance analysis (BIA) phase-sensitive system. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Dietary vitamin D intake data was collected by three-day food records. The 25OHD levels in the PWS adults were constantly lower across all categories of BMI and fat mass compared with their obese counterpart. The 25OHD levels were negatively associated with BMI (p = 0.04), waist circumference (p = 0.03), fat mass (p = 0.04), and dietary vitamin D intake (p &lt; 0.001). During multiple regression analysis, dietary vitamin D intake was entered at the first step (p &lt; 0.001), thus explaining 84% of 25OHD level variability. The threshold values of BMI and fat mass predicting the lowest decrease in the 25OHD levels were found at BMI &ge; 42 kg/m2 (p = 0.01) and fat mass &ge; 42 Kg (p = 0.003). In conclusion, our data indicate that: (i) 25OHD levels and dietary vitamin D intake were lower in PWS adults than in the control, independent of body fat differences; (ii) 25OHD levels were inversely associated with BMI, waist circumference, and fat mass, but low dietary vitamin D intake was the major determinant of low vitamin D status in these patients; (iii) sample-specific cut-off values of BMI and fat mass might help to predict risks of the lowest 25OHD level decreases in PWS adults. The presence of trained nutritionists in the integrated care teams of PWS adults is strongly suggested in order to provide an accurate nutritional assessment and tailored vitamin D supplementations

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

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

A New Light on Vitamin D in Obesity: A Novel Association with Trimethylamine-N-Oxide (TMAO)

Vitamin D deficiency and obesity are two public health problems extensively exacerbated over the last years. Among the several mechanisms proposed to account for the complex interplay between vitamin D and obesity, one that has gained particular attention is related to the emerging role of obesity-related changes in gut microbiota and gut-derived metabolites, such as Trimethylamine-N-oxide (TMAO). Vitamin D deficiency and high circulating TMAO levels are associated with body weight and the severity of non-alcoholic fatty liver disease (NAFLD). Considering the link of obesity with vitamin D on the one hand and obesity with TMAO on the other hand, and the central role of the liver in both the vitamin D and TMAO metabolism, the aim of this cross-sectional observational study was first, to confirm the possible inverse association between vitamin D and TMAO across different body mass index (BMI) classes and second, to investigate if this association could be influenced by the presence of NAFLD. One hundred and four adult subjects (50 males and 54 females; 35.38 &plusmn; 7.49 years) were enrolled. The fatty liver index (FLI) was used as a proxy for the diagnosis of NAFLD. Vitamin D deficiency was found in 65 participants (62.5%), while 33 subjects (31.7%) had insufficient levels, and the remaining subjects had sufficient levels of vitamin D. Subjects with both vitamin D deficiency and FLI-NAFLD had the highest TMAO levels (p &lt; 0.001). By stratifying the sample population according to the BMI classes, vitamin D levels decreased significantly along with the increase of plasma TMAO concentrations, with the lowest vitamin D levels and highest TMAO, respectively, in class III obesity. Vitamin D levels showed significant opposite associations with circulating levels of TMAO (r = &minus;0.588, p &lt; 0.001), but this association was no longer significant after the adjustment for FLI values. The highest values of TMAO were significantly associated with the severity of obesity (OR 7.92; p &lt; 0.001), deficiency of vitamin D (OR 1.62; p &lt; 0.001), and FLI-NAFLD (OR 3.79; p &lt; 0.001). The most sensitive and specific cut-off for vitamin D to predict the circulating levels of TMAO was &le;19.83 ng/mL (p &lt; 0.001). In conclusion, our study suggests that high TMAO levels are associated with vitamin D deficiency and NAFLD. Further studies are required to investigate if there is a causality link or whether all of them are simply the consequence of obesity