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Although it has been recognized for almost two centuries, myocarditis is still a challenging diagnosis due to the wide heterogeneity of its clinical manifestations and evolution. Moreover, the diagnostic gold standard, endomyocardial biopsy (EMB), is infrequently used, making hard to determine the exact incidence of myocarditis. Clinical presentation includes a wide range of symptoms, ranging from asymptomatic or subclinical disease with mild dyspnea and chest pain to sudden death, due to cardiogenic shock or malignant ventricular arrhythmias. Equally, the evolution of myocarditis largely varies: albeit short-term prognosis is usually good, with complete or partial recovery, dilated cardiomyopathy with chronic heart failure is the major long-term consequence of myocarditis, developing often several years after the acute onset. This narrative review aims to summarize the current knowledge about myocarditis, with a particular attention to predictors of short- and long-term prognosis, in order to provide a rational and practical approach to the diagnosis, evaluation and treatment of suspected myocarditis.

AimsTo explore variables associated with the serological response following COVID-19 mRNA vaccine.MethodsHealthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by three weeks. Blood samples were collected before the first and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry.ResultsEighty-six patients were enrolled. Those with central obesity had lower antibody (Ab) titers compared with those with no central obesity [1426(1436)vs1971(1819), p=0.04]; smokers had a blunted response compared to non-smokers [1099(1350)vs1921(1375), p=0.007], as well as hypertensive vs normotensive [650±1192vs1911(1364), p=0.001] and dyslipidemic compared to those with normal serum lipids [534(972)vs 1872(1406), p=0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension and longer time elapsed since second vaccine inoculation were associated with lower Ab titers, independent of BMI, age and gender. The association between waist circumference and Ab titers was lost when controlling for body fat, suggesting that visceral accumulation may explain this result.ConclusionsIt is currently impossible to determine whether lower SARS CoV-2 Abs lead to higher likelihood of developing COVID-19. However, neutralizing abs correlate with protection against several viruses including SARS-CoV-2, and the finding that central obesity, hypertension and smoking are associated with a blunted response warrants further attention. Our findings must lead to a vigilant approach, as these subjects could benefit from earlier vaccine boosters or different vaccine schedules.

Idiopathic Intracranial Hypertension is a neurological disorder primarily affecting overweight women of childbearing age. It is often characterized by radiologic evidence of empty sella (ES), which is in turn frequently associated with pituitary dysfunction, with the somatotropic axis most commonly affected. No recent evidence is available relative to the presence of pituitary hormone deficiencies in adult patients with Idiopathic Intracranial Hypertension (IIH) under pharmacological therapy. We therefore explored pituitary function and morphology in a small cohort of female patients with IIH treated with acetazolamide. Fifteen female patients aged 42 ± 13 years with IIH lasting between 12 and 18 months were evaluated. All patients were affected by recurrent headaches in addition to visual changes of variable severity. IIH diagnosis was made after exclusion of other causes of raised intracranial pressure, and a specific ophthalmological evaluation was conducted to assess for the presence of papilledema. No particular endocrinological disturbances were detected during the enrolment visits, except for a high obesity prevalence (87%, BMI 35.16 ± 8.21 kg/m2), one case of total thyroidectomy for papillary thyroid carcinoma and two patients with irregular menses and mild hirsutism. All the participants underwent a pituitary MRI with contrast, and two different operators performed pituitary measurements in coronal and sagittal scans for morphologic assessment. Blood samples for the anterior pituitary axis evaluation were collected, and the somatotropic axis was further evaluated with a GHRH + Arginine test; other dynamic tests were performed in case of suspected hormonal deficiency. Despite ES being found in 73% of the patients, pituitary volume was preserved, ranging from 213.85 to 642.27mm3 (389.20 ± 125.53mm3); mean coronal pituitary height was 4.53 ± 1.33 mm. Overall, baseline anterior pituitary hormones levels were within normal ranges, and none of the patients with ES had an altered response to the GHRH + arginine stimulation test. We found one patient suffering from iatrogenic hyperthyroidism and two diagnosed with subclinical primary hypothyroidism due to Hashimoto’s thyroiditis. Two young patients were suspected of having polycystic ovary syndrome, and they were therefore further investigated. In conclusion, this case series shows that, despite the high prevalence of ES, the pituitary function of IIH patients treated with acetazolamide is preserved. To date, there is no evidence regarding the trend over time or upon treatment discontinuation in regard to the pituitary function of patients with IIH, and it is therefore not possible to infer whether our finding would be replicable in such settings. We therefore suggest an endocrine follow-up over time in order to monitor for potential pituitary dysfunction.

Aims To explore variables associated with the serological response following COVID‐19 mRNA vaccine. Methods Eighty‐six healthcare workers adhering to the vaccination campaign against COVID‐19 were enrolled in January–February 2021. All subjects underwent two COVID‐19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by 3 weeks. Blood samples were collected before the 1st and 1–4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual‐energy‐X‐ray absorptiometry. Results Higher waist circumference was associated with lower antibody (Ab) titres (R = −0.324, p = 0.004); smokers had lower levels compared to non‐smokers [1099 (1350) vs. 1921 (1375), p = 0.007], as well as hypertensive versus normotensive [650 ± 1192 vs. 1911 (1364), p = 0.001] and dyslipideamic compared to those with normal serum lipids [534 (972) vs 1872 (1406), p = 0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension, and longer time elapsed since second vaccine inoculation were associated with lower Ab titres, independent of BMI, age. and gender. Conclusions Central obesity, hypertension, and smoking are associated with lower Ab titres following COVID‐19 vaccination. Although it is currently impossible to determine whether lower SARS‐CoV‐2 Abs lead to higher likelihood of developing COVID‐19, it is well‐established that neutralizing antibodies correlate with protection against several viruses including SARS‐CoV‐2. Our findings, therefore, call for a vigilant approach, as subjects with central obesity, hypertension, and smoking could benefit from earlier vaccine boosters or different vaccine schedules.

Severe obesity is associated with an increased risk of admission to intensive care units and need for invasive mechanical ventilation in patients with COVID-19. The association of obesity and COVID-19 prognosis may be related to many different factors, such as chronic systemic inflammation, the predisposition to severe respiratory conditions and viral infections. The ketogenic diet is an approach that can be extremely effective in reducing body weight and visceral fat in the short term, preserving the lean mass and reducing systemic inflammation. Therefore, it is a precious preventive measure for severely obese people and may be considered as an adjuvant therapy for patients with respiratory compromise.

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited—besides lowering blood glucose levels—direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug–drug interactions with anti-platelet agents. We aimed at expanding clinicians’ understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies.

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan&ndash, Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model.

Background Obesity was recently identified as a major risk factor for worse COVID-19 severity, especially among the young. The reason why its impact seems to be less pronounced in the elderly may be due to the concomitant presence of other comorbidities. However, all reports only focus on BMI, an indirect marker of body fat. Aim To explore the impact on COVID-19 severity of abdominal fat as a marker of body composition easily collected in patients undergoing a chest CT scan. Methods Patients included in this retrospective study were consecutively enrolled among those admitted to an Emergency Department in Rome, Italy, who tested positive for SARS-Cov-2 and underwent a chest CT scan in March 2020. Data were extracted from electronic medical records. Results 150 patients were included (64.7% male, mean age 64 ± 16 years). Visceral fat (VAT) was significantly higher in patients requiring intensive care (p = .032), together with age (p = .009), inflammation markers CRP and LDH (p, Highlights • High BMI is a risk factor of COVID-19 severity especially among the young • BMI in an indirect marker of body fat excess • COVID-19 patients routine chest CT scan may be leveraged to directly quantify body fat • Visceral fat deposition is higher in COVID-19 patients accessing ICU • Visceral fat is associated with the need of intensive care (OR = 2.474)

Evidence has lately emerged regarding an increased risk of SARS-CoV-2 with worse prognosis in patients with obesity, especially among the young. Weight excess is a well-established respiratory disease risk factor, and the newly reported correlation is therefore unsurprising. The underlying pathophysiology is likely multi-stranded, ranging from complement system hyperactivation, increased Interleukin-6 secretion, chronic inflammation, presence of comorbidities such as diabetes and hypertension, and a possible local, detrimental effect within the lung. Further understanding the link between obesity and SARS-CoV-2 is crucial, as this could aid proper tailoring of immunomodulatory treatments, together with improving stratification among those possibly requiring critical care.

The prevalence of obesity is soaring all over the world, and Italy is reaching the same pace. Similar to other countries, the Italian healthcare system counts on a three-tier model for obesity care, and each region has freedom in the implementation of guidelines. No national record is currently available to monitor the actual situation throughout the country. To provide a report of the current status on the availability of specialized public obesity care services in Italy. Regional prevalence of obesity was extrapolated from publicly available data. Data on facilities for the management of obesity were retrieved from records provided by national scientific societies. Whenever possible, data was verified through online research and direct contact. We report a north–south and east–west gradient regarding the presence of obesity focused facilities, with an inverse correlation with the regional prevalence of obesity (R = 0.25, p = 0.03). Medical-oriented centers appear homogeneous in the multidisciplinary approach, the presence of a bariatric surgery division, the availability of support materials and groups, with no major difference on follow-up frequency. Surgery-oriented centers have a more capillary territorial distribution than the medically oriented, but not enough data was retrieved to provide a thorough description of their characteristics. Obtaining a clear picture of the situation and providing consistent care across the country is a challenging task due to the decentralized organization of regions. We provide a first sketch, reporting that the model is applied unevenly, and we suggest feasible actions to improve the situation in our country and elsewhere. Level V, narrative review.

Background. Short-term interventions based on very low-calorie ketogenic diets (VLCKDs) and meal replacements may be prescribed to selected overweight or obese patients. Few, inconsistent data are available on protein intake from various sources on body weight, composition of gut microbiota and metabolic outcomes in these patients. Aim. To compare efficacy, safety and effect on microbiota composition of short-term isocaloric very low-calorie ketogenic diets encompassing whey, vegetable or animal proteins, in obese patients with insulin resistance. Materials and Methods. 48 obese patients (19 males and 29 females) with HOMA-index ≥ 2.5, age mean: 55.2 years (range: 45-73), BMI mean 35.9 kg/m2 (range: 30.2 - 46.4) were randomly assigned to three isocaloric VLCKD regimens (≤800 kcal/day) containing either whey, plant or animal proteins for 45 days, with assessments of anthropometric indexes, blood and urine chemistry, body composition, muscle strength, taxonomic composition of the gut microbiome. Results. A significant reduction of body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, total and LDL cholesterol was observed in all the patients, regardless the dietary protein source. Patients fed with whey proteins and vegetable proteins had a more pronounced decrease of visceral adipose tissue (VAT) compared with the group fed with animal proteins. The markers of renal function slightly worsened in the group fed with animal proteins. A decrease in relative abundance of Firmicutes and an increase of Bacteroidetes was observed after VLCKDs. This pattern was less pronounced in patients consuming animal proteins. Conclusions. VLCKDs lead to significant weight loss and a striking improvement of the metabolic parameters over a short period of time. VLCKDs based on whey or vegetable proteins induce a larger reduction of VAT, have a safer profile and determine a healthier microbiota composition compared to those containing animal proteins.

Context We compared the efficacy, safety, and effect of 45-day isocaloric very-low-calorie ketogenic diets (VLCKDs) incorporating whey, vegetable, or animal protein on the microbiota in patients with obesity and insulin resistance to test the hypothesis that protein source may modulate the response to VLCKD interventions. Subjects and Methods Forty-eight patients with obesity (19 males and 29 females, homeostatic model assessment (HOMA) index ≥ 2.5, aged 56.2 ± 6.1 years, body mass index [BMI] 35.9 ± 4.1 kg/m2) were randomly assigned to three 45-day isocaloric VLCKD regimens (≤800 kcal/day) containing whey, plant, or animal protein. Anthropometric indexes; blood and urine chemistry, including parameters of kidney, liver, glucose, and lipid metabolism; body composition; muscle strength; and taxonomic composition of the gut microbiome were assessed. Adverse events were also recorded. Results Body weight, BMI, blood pressure, waist circumference, HOMA index, insulin, and total and low-density lipoprotein cholesterol decreased in all patients. Patients who consumed whey protein had a more pronounced improvement in muscle strength. The markers of renal function worsened slightly in the animal protein group. A decrease in the relative abundance of Firmicutes and an increase in Bacteroidetes were observed after the consumption of VLCKDs. This pattern was less pronounced in patients consuming animal protein. Conclusions VLCKDs led to significant weight loss and a striking improvement in metabolic parameters over a 45-day period. VLCKDs based on whey or vegetable protein have a safer profile and result in a healthier microbiota composition than those containing animal proteins. VLCKDs incorporating whey protein are more effective in maintaining muscle performance.

The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is an effective weight loss procedure. The gastro-jejunal (GJ) anastomosis required can be performed on the anterior or posterior gastric pouch wall. No studies have compared these variants in terms of efficacy and onset of dumping syndrome (DS) and weight regain (WR). We aimed at assessing the prevalence of DS in relation to the site of anastomosis together with identifying prognostic factors of DS and WR. Patients who had undergone LRYGB with anterior (AGJ) or posterior (PGJ) anastomosis in 2010–2019 were retrospectively analyzed. We collected demographic data, medical history and the prevalence of DS evaluated through the Sigstad Score, together with WR data. 213 patients were enrolled, of which 51.6% had an AGJ and 48.4% had a PGJ. The mean follow-up time was 81 ± 18 and 27 ± 13 months in the AGJ and PGJ group, respectively (p

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion, 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation.

AIM To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D). MATERIALS AND METHODS Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption. RESULTS GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend. CONCLUSIONS In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, and with leptin and adiponectin, it regulates metabolic homeostasis. Widely studied in tissues, SIRT1 is under evaluation as a plasmatic marker. We aimed at assessing whether circulating SIRT1 behaves consistently with leptin and adiponectin in conditions of deficiency, excess or normal fat content. Eighty subjects were evaluated: 27 with anorexia nervosa (AN), 26 normal-weight and 27 with obesity. Bloodstream SIRT1, leptin and adiponectin (ELISA), total and trunk fat mass (FM) %, abdominal visceral adipose tissue, liver steatosis and epicardial fat thickness (EFT) were assessed. For each fat store, the coefficient of determination (R2) was used to evaluate the prediction capability of SIRT1, leptin and adiponectin. Plasma SIRT1 and adiponectin coherently decreased with the increase of FM, while the opposite occurred with leptin. Mean levels of each analyte were different between groups (p &lt, 0.005). A significant association between plasma variables and FM depots was observed. SIRT1 showed a good predictive strength for FM, particularly in the obesity group, where the best R2 was recorded for EFT (R2 = 0.7). Blood SIRT1, adiponectin and leptin behave coherently with FM and there is synchrony between them. The association of SIRT1 with FM is substantially superimposable to that of adiponectin and leptin. Given its homeostatic roles, SIRT1 may deserve to be considered as a plasma clinical/biochemical parameter of adiposity and metabolic health.

Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure.

Summary First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient‐to‐patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p &lt, 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.

Myocarditis is an uncommon but potentially life-threatening disease. Clinical manifestations could range from subclinical disease to sudden death, due to fulminant heart failure and/or malignant ventricular arrhythmias. The most common cause of myocarditis is viral infection, including Epstein-Barr virus (EBV). Nevertheless, EBV rarely presents with cardiac involvement in immunocompetent hosts. We report a case of acute EBV-related myocarditis in a young female, complicated with malignant ventricular arrhythmias and cardiac arrest. After 20 days of hospitalization and treatment, the patient was fit for discharge on pharmacological therapy (tapering steroids, beta-blockers, amiodarone, angiotensin-converting enzyme inhibitors, and diuretics). Clinical course is described, cardiac magnetic resonance images are shown. This case underlines how myocarditis is a disease that should not be underestimated: it could present with life-threatening complications such as malignant arrhythmias and/or severe systolic dysfunction.

BACKGROUND: Fibroblast Growth Factor 21 (FGF21) is expressed in several metabolically active tissues, including liver, fat and acinar pancreas, and has pleiotropic effects on metabolic homeostasis. The dominant source of FGF21 in the circulation is the liver. OBJECTIVE AND METHODS: To analyze the physiological functions of hepatic FGF21, we generated a hepatocyte specific knockout model (LKO) by mating albumin-Cre mice with FGF21 flox/flox (fl/fl) mice and challenged it with different nutritional models. RESULTS: Mice fed a ketogenic diet typically show increased energy expenditure; this effect was attenuated in LKO mice. LKO on KD also developed hepatic pathology and altered hepatic lipid homeostasis. When evaluated using hyperinsulinemic euglycemic clamps, glucose infusion rates, hepatic glucose production and glucose uptake were similar between fl/fl and LKO DIO mice. CONCLUSIONS: We conclude that liver derived FGF21 is important for complete adaptation to ketosis but has a more limited role in the regulation of glycemic homeostasis.

Vitamin K is a liposoluble vitamin. The predominant dietary form, phylloquinone or vitamin K1, is found in plants and green vegetables; whereas menaquinone, or vitamin K2, is endogenously synthesized by intestinal bacteria and includes several subtypes that differ in side chain length. Aside from its established role in blood clotting, several studies now support a critical function of vitamin K in improving bone health. Vitamin K is in fact required for osteocalcin carboxylation that in turn regulates bone mineral accretion; it seems to promote the transition of osteoblasts to osteocytes and also limits the process of osteoclastogenesis. Several observational and interventional studies have examined the relationship between vitamin K and bone metabolism, but findings are conflicting and unclear. This systematic review aims to investigate the impact of vitamin K (plasma levels, dietary intake, and oral supplementation) on bone health with a particular interest in bone remodeling, mineral density and fragility fractures.

Objective Excess ethanol consumption has serious pathologic consequences. In humans, repeated episodes of binge drinking can lead to liver damage and have adverse effects on other organs such as pancreas and brain. Long term chronic consumption of ethanol can also result in progressive alcoholic liver disease and cirrhosis. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. FGF21 is a novel biomarker for non-alcoholic fatty liver disease (NAFLD) in humans and limits hepatotoxicity in mice. Therefore, we explored the possibility that FGF21 plays a role in response to ethanol consumption in both humans and mice. Methods We used a binge drinking paradigm in humans to examine the effect of acute ethanol consumption on circulating FGF21. We adapted this paradigm to evaluate the acute response to ethanol in mice. We then examined the role of FGF21 on liver pathology in two models of chronic ethanol consumption in both wild type (WT) mice and mice lacking FGF21 (FGF21-KO). Results Acute ethanol consumption resulted in a robust induction of serum FGF21 after 6 h in both humans and mice. Serum ethanol peaked at 1 h in both species and was cleared by 6 h. Ethanol clearance was the same in WT and FGF21-KO mice, indicating that FGF21 does not play a major role in ethanol metabolism in a binge paradigm. When FGF21-KO mice were fed the Lieber–DeCarli diet, a high fat diet supplemented with ethanol, a higher mortality was observed compared to WT mice after 16 days on the diet. When FGF21-KO mice consumed 30% ethanol in drinking water, along with a normal chow diet, there was no mortality observed even after 16 weeks, but the FGF21-KO mice had significant liver pathology compared to WT mice. Conclusions Acute or binge ethanol consumption significantly increases circulating FGF21 levels in both humans and mice. However, FGF21 does not play a role in acute ethanol clearance. In contrast, chronic ethanol consumption in the absence of FGF21 is associated with significant liver pathology alone or in combination with excess mortality, depending on the type of diet consumed with ethanol. This suggests that FGF21 protects against long term ethanol induced hepatic damage and may attenuate progression of alcoholic liver disease. Further study is required to assess the therapeutic potential of FGF21 in the treatment of alcoholic liver disease., Highlights • Binge ethanol consumption robustly increases circulating FGF21 levels in both humans and mice. • FGF21 does not play a role in ethanol clearance which is the same in WT and FGF21-KO mice. • In mice lacking FGF21, in two models of ethanol consumption there was either excess mortality or excess hepatic damage and inflammation. • These data suggest the FGF21 may have potential therapeutic value for alcoholic liver disease.

Recent evidence demonstrating an increased fracture risk among obese individuals suggests that adipose tissue may negatively impact bone health, challenging the traditional paradigm of fat mass playing a protective role towards bone health. White adipose tissue, far from being a mere energy depot, is a dynamic tissue actively implicated in metabolic reactions, and in fact secretes several hormones called adipokines and inflammatory factors that may in turn promote bone resorption. More specifically, Visceral Adipose Tissue (VAT) may potentially prove detrimental. It is widely acknowledged that obesity is positively associated to many chronic disorders such as metabolic syndrome, dyslipidemia and type 2 diabetes, conditions that could themselves affect bone health. Although aging is largely known to decrease bone strength, little is yet known on the mechanisms via which obesity and its comorbidities may contribute to such damage. Given the exponentially growing obesity rate in recent years and the increased life expectancy of western countries it appears of utmost importance to timely focus on this topic.

This report describes a case of carcinosarcoma of the duodenum. Carcinosarcoma of the duodenum is a very rare tumor. A 72-year-old man was referred to the hospital because of appetite loss. Endoscopy demonstrated an irregularly depressed lesion (type 3) in the descending portion of the duodenum opposite to the ampulla of Vater. Computed tomography showed a thickened duodenal wall and swelling of the abdominal para-aortic lymph nodes. A biopsy specimen revealed a well-differentiated adenocarcinoma. A diagnosis of duodenal carcinoma was made (cT3, cN1, cM1, cStage IV according to the TNM classification). A subtotal stomach-preserving pancreatoduodenectomy and a lymph node resection were performed. On microscopic examination, adenocarcinoma cells and spindle type sarcoma cells were observed separately in the descending portion of the duodenum opposite to the ampulla of Vater. The adenocarcinoma cells were stained with antibodies against epithelial markers keratin and carcinoembryonic antigen for immunohistochemical analyses. In contrast, the sarcoma cells were stained with antibodies to vimentin and smooth muscle actin. The pathological diagnosis of a true duodenal carcinosarcoma was thus made.

はじめに:外科レジデントが執刀したセンチネルリンパ節生検（以下，SLNBと略記）について，その安全性と妥当性を検証したので報告する．方法:外科レジデントが執刀した，RI・色素併用法によるSLNB併用乳癌手術症例50例を対象（Study群）とし，外科指導医が執刀した60例をControl群としてretrospectiveな比較検討を行った．結果:Study群とControl群の同定率はそれぞれ98.0％と100％で，両群とも良好であった．両群間の合併症発生率は差がなく，SLNBに関連する合併症はseromaのみで，その発生率はStudy群4例（8.0％），Control群3例（5.0％）であった．考察:RI・色素併用法によるSLNBはレジデント執刀でも安全で，高い同定率が確保できることが確認できた．

Obesity can nowadays be considered a disease with a multifactorial origin. Genes, socioeconomic status, dietary patterns, and psychological profile are only some of the factors that may lead to excess body weight and its deleterious outcomes. A correct assessment of an obese patient cannot be merely limited to weight evaluation, it must consider other aspects such as, among others, biochemical parameters, clinical conditions, and physical fitness. Given its complexity, it has been demonstrated that a multidisciplinary approach is more effective than a single-clinician one in terms of weight loss and comorbidities improvement. Ideally, an obesity management team should be composed of several health professionals such as endocrinologist, clinical nutritionist, a psychiatrist, a bariatric surgeon, and a physiatrist together with other health professionals (i.e., dietitian, psychologist, physiotherapist, nurse). In order to manage every obese subject in an effective manner, different levels of care should be considered: primary care, outpatient clinics held by a multidisciplinary equipe, day hospital, residential rehabilitation treatment, and hospitalization. Although an interdisciplinary approach is advisable in treating obesity, some disadvantages must be considered. In case of a defective communication among team members, there is a risk of losing the full picture of the patient who in turn could receive conflicting advice from each health professional. Moreover, multidisciplinary approach is much more time-consuming than a diet-only treatment, limiting its accessibility to those whose schedules are very flexible. In conclusion, an interdisciplinary approach is to be considered the treatment of choice in the obese patient, but a lot is still to be improved, especially in terms of health professionals’ education to teamwork.

Stefania Mariani,1 Daniela Fiore,1 Laura Varone,2 Sabrina Basciani,1 Agnese Persichetti,1 Mikiko Watanabe,1 Maurizio Saponara,3 Giovanni Spera,1 Costanzo Moretti,4 Lucio Gnessi11Department of Experimental Medicine, Section of Medical Physiopathology and Endocrinology, Sapienza University of Rome, Italy; 2Department of Environmental Biology, Sapienza University of Rome, Italy; 3Department of Otolaryngology, Audiology and Phonation, Sapienza University of Rome, Italy; 4Division of Endocrinology, Department of System Medicine, Section of Reproductive Endocrinology University of TorVergata, Fatebenefratelli Hospital "San Giovanni Calibita" Rome, ItalyContext: Obesity and its co-morbidities may adversely affect bone mineral density (BMD). Obstructive sleep apnea (OSA) is a major complication of obesity. To date, the effects of OSA on BMD in obese patients have been poorly studied.Objective: To examine whether the severity of OSA independently correlates with BMD in obese patients.Methods: One hundred and fifteen obese subjects with OSA (Apnea/Hypopnea Index [AHI] ≥5 events per hour) were included in the study. BMD was measured at lumbar spine, total hip, and femoral neck by dual energy X-ray absorptiometry. Body mass index, lean mass, and representative measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL-cholesterol, triglycerides) and inflammation (ESR, CRP, fibrinogen) were also evaluated.Results: BMD did not differ among obese individuals regardless of OSA severity. Correlation coefficient analysis for all the covariates showed a lack of association between AHI and BMD that was strongly influenced by age and weight.Conclusion: Our study does not support an independent association between AHI and BMD in obese patients. Controlled studies involving a greater number of patients are warranted.Keywords: obesity, polysomnography, metabolic syndrome

Osteoclasts modulate bone resorption under physiological and pathological conditions. Previously, we showed that both estrogens and retinoids regulated osteoclastic bone resorption and postulated that such regulation was directly mediated through their cognate receptors expressed in mature osteoclasts. In this study, we searched for expression of other members of the nuclear hormone receptor superfamily in osteoclasts. Using the low stringency homologous hybridization method, we isolated the peroxisome proliferator-activated receptor delta/beta (PPARdelta/beta) cDNA from mature rabbit osteoclasts. Northern blot analysis showed that PPARdelta/beta mRNA was highly expressed in highly enriched rabbit osteoclasts. Carbaprostacyclin, a prostacyclin analogue known to be a ligand for PPARdelta/beta, significantly induced both bone-resorbing activities of isolated mature rabbit osteoclasts and mRNA expression of the cathepsin K, carbonic anhydrase type II, and tartrate-resistant acid phosphatase genes in these cells. Moreover, the carbaprostacyclin-induced bone resorption was completely blocked by an antisense phosphothiorate oligodeoxynucleotide of PPARdelta/beta but not by the sense phosphothiorate oligodeoxynucleotide of the same DNA sequence. Our results suggest that PPARdelta/beta may be involved in direct modulation of osteoclastic bone resorption.