Postbariatric surgery hypoglycemia: Nutritional, pharmacological and surgical perspectives.

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition.

Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Noninvasive assessment of histological features of nonalcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple noninvasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic nonalcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score ≥4, and fibrosis stage ≥2. METHODS: The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in 3 independent European cohorts (Finland, n = 370; Italy, n = 947; England, n = 5368) of individuals at high risk for NAFLD. RESULTS: The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase, high-density lipoprotein cholesterol, and hemoglobin A1c. The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROC = 0.78 and AUROC = 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cutoffs were 0.10 for sensitivity ≥0.89 (negative predictive value, 0.93) and 0.33 for specificity ≥0.90 (positive predictive value, 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (negative predictive value, 0.99-1) and specificity from 0.73 to 0.94 (positive predictive value, 0.12-0.49) for rule-out and rule-in cutoff, respectively. CONCLUSION: FNI is an accurate, simple, and affordable noninvasive score which can be used to screen for fibrotic NASH in individuals with dysmetabolism in primary health care.

Central obesity, smoking habit, and hypertension are associated with lower antibody titres in response to COVID-19 mRNA vaccine.

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.

An extra virgin olive oil-enriched chocolate spread positively modulates insulin-resistance markers compared with a palm oil-enriched one in healthy young adults: A double-blind, cross-over, randomised controlled trial.

AIMS: To investigate if extra virgin olive oil (EVOO) or palm oil enriched chocolate spreads consumption leads to different results in terms of plasma ceramides concentration, glucose and lipid metabolism, inflammatory markers and appetite regulation in young healthy subjects. METHODS: In a 2-week, double-blind, cross-over, randomised controlled trial, 20 healthy, normal-weight subjects with a mean age of 24.2 years (SD: 1.2), consumed chocolate spread snacks (73% of energy [%E] from fat, 20% from carbohydrates and 7% from proteins), providing 570 Kcal/day added to an isocaloric diet. The chocolate spreads were identical, except for the type of fat: EVOO oil, rich in monounsaturated fatty acids (MUFAs), or palm oil, rich in Saturated Fatty Acids (SFAs). RESULTS: EVOO-enriched chocolate spread consumption led to better circulating sphingolipids and glucose profile, with reduced plasma ceramide C16:0, ceramide C16:0/ceramide C22:0-ceramide C24:0 ratio and sphingomyelin C18:0 (P = 0.030, P= 0.032 and P = 0.042, respectively) compared to the palm oil-enriched chocolate spread diet. HOMA-IR and plasma insulin were lower, while the Quicki and the McAuley Index were higher after the EVOO diet compared to the palm oil diet (P = 0.046, P = 0.045, P = 0.018 and P = 0.039 respectively). Subjects maintained a stable weight throughout the study. No major significant changes in total cholesterol, triglycerides, HDL, inflammatory markers, and appetite-regulating hormones/visual analogue scale were observed between the groups. CONCLUSIONS: Partially replacing SFAs with MUFAs in a chocolate-based snack as part of a short-term isocaloric diet in healthy individuals may limit SFAs detrimental effects on insulin sensitivity and decrease circulating harmful sphingolipids in young adults.

Accuracy of controlled attenuation parameter for assessing liver steatosis in individuals with morbid obesity before bariatric surgery.

BACKGROUND & AIMS: The ultrasound-based controlled attenuation parameter (CAP) is a non-invasive tool widely validated for assessing liver steatosis across different etiologies. However, few studies, with liver biopsy available, have investigated its performance in individuals with morbid obesity. Herein, we aimed to evaluate the diagnostic accuracy of CAP in participants with morbid obesity from the MAFALDA study before bariatric surgery. METHODS: A total of 120 individuals with valid examinations within three months from bariatric surgery were included. Clinical, laboratory, FibroScan® (XL probe), and liver biopsy data were collected using standardized procedures. The overall accuracy of CAP for detecting liver steatosis was estimated by the area under the receiver-operating characteristics curve (AUROC). Optimal cut-offs were chosen at points with the highest Youden index. RESULTS: The AUROCs of CAP for detecting S ≥ S1, S ≥ S2, and S = S3 were 0.91 (95% CI 0.86-0.97), 0.83 (95% CI 0.76-0.90), and 0.86 (95% CI 0.79-0.94), respectively. The best CAP cut-offs for S ≥ S1, S ≥ S2, and S = S3 were 300 dB/m (95% CI 275-316), 328 dB/m (95% CI 296-345), and 344 dB/m (95% CI 343-352), respectively. CAP values were independently influenced by steatosis grade (estimate 20.60, 95% CI 12.70-28.40, P = 1.05 × 10-6 ). The AUROC of FibroScan-AST (FAST) score for detecting progressive non-alcoholic steatohepatitis was 0.76 (95% CI 0.66-0.86). CONCLUSIONS: In individuals with morbid obesity, CAP measured by XL probe is an accurate non-invasive tool for grading liver steatosis. Measurement of liver fat content by CAP may help identify those eligible for bariatric procedures and estimate the effect of bariatric surgery on hepatic steatosis. LAY SUMMARY: The ultrasound-based controlled attenuation parameter (CAP) by using the XL probe has an excellent performance for grading liver steatosis among individuals with morbid obesity. CAP may represent an accurate tool for the non-invasive assessment of liver steatosis among individuals with morbid obesity before and after bariatric surgery.

Neck circumference as reliable predictor of mechanical ventilation support in adult inpatients with COVID-19: A multicentric prospective evaluation.

AIMS: COVID-19 is especially severe for elderly subjects with cardiometabolic and respiratory comorbidities. Neck circumference (NC) has been shown to be strongly related to cardiometabolic and respiratory illnesses even after adjustment for body mass index (BMI). We performed a prospective study to investigate the potential of NC to predict the need for invasive mechanical ventilation (IMV) in adult COVID-19 inpatients. MATERIALS AND METHODS: We prospectively and consecutively enrolled COVID-19 adult patients admitted to dedicated medical wards of two Italian hospitals from 25 March to 7 April 2020. On admission, clinical, biochemical and anthropometric data, including BMI and NC were collected. As primary outcome measure, the maximum respiratory support received was evaluated. Follow-up time was 30 days from hospital admission. RESULTS: We enrolled 132 subjects (55.0-75.8 years, 32% female). During the study period, 26 (19.7%) patients underwent IMV. In multivariable logistic regression analyses, after adjusting for age, sex, diabetes, hypertension and COPD, NC resulted independently and significantly associated with IMV risk (adjusted OR 1.260-per 1 cm increase 95% CI:1.120-1.417; P < .001), with a stronger association in the subgroup with BMI ≤30 Kg/m2 (adjusted OR 1.526; 95% CI:1.243-1.874; P < .001). NC showed a good discrimination power in predicting patients requiring IMV (AUC 0.783; 95% CI:0.684-0.882; P < .001). In particular, NC > 40.5 cm (>37.5 for females and >42.5 for males) showed a higher and earlier IMV risk compared to subjects with lower NC (Log-rank test: P < .001). CONCLUSIONS: NC is an easy to measure parameter able to predict the need for IMV in adult COVID-19 inpatients.

The Mediterranean diet increases glucagon-like peptide 1 and oxyntomodulin compared with a vegetarian diet in patients with type 2 diabetes: A randomized controlled cross-over trial.

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.

Effects of the COVID-19 lockdown on glycaemic control in subjects with type 2 diabetes: the glycalock study.

AIM: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). RESULTS: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group -0.1% [-0.5%-0.3%] vs. control group -0.1% [-0.4%-0.2%]; p = .482). Also, no difference was found in ΔBMI (p = .316) or ΔGlucose (p = .538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p = .041 for the trend among PGWBS tertiles) and BMI (p = .022). CONCLUSIONS: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended.

Bone Quality as Measured by Trabecular Bone Score in Normocalcemic Primary Hyperparathyroidism.

OBJECTIVE: The impact of normocalcemic hyperparathyroidism (NHPT) on bone quality remains largely unexplored. We aimed to investigate the usefulness of trabecular bone score (TBS) assessment in NHPT and the accuracy of TBS in predicting vertebral fractures (VFs) in NHPT. METHODS: In this multicentric cross-sectional study, we assessed the TBS in 47 subjects with NHPT, 41 with primary hyperparathyroidism (PHPT), and 39 age- and sex-matched control subjects. RESULTS: TBS values did not differ among the 3 groups. The prevalence of low TBS (TBS < 1.2) was 23.4% in NHPT, 26.8% in PHPT, and 15.4% in controls, without statistically significant differences between groups. However, we found a lower lumbar spine Z-score adjusted for TBS (LS Z-score∗TBS) in PHPT participants when compared with controls (-0.48 ± 1.06 vs 0.07 ± 0.93, P = .017). In NHPT group, LS Z-score∗TBS did not detect patients with overall VFs (threshold, -0.15; area under the curve, 0.45; 95% CI, 0.253-0.648; accuracy, 55.3%). Instead, it was useful for moderate-severe VFs (threshold, 0.55; area under the curve, 0.81; 95% CI, 0.62-0.996; accuracy, 83%). In PHPT subjects also, TBS did not predict VFs. CONCLUSION: In NHPT, TBS is not reduced. When adjusted for TBS, the LS Z-score might predict moderate-to-severe VFs.

Liver disease in obesity and underweight: the two sides of the coin. A narrative review.

PURPOSE: Malnutrition, whether characterized by not enough or too much nutrient intake, is detrimental to the liver. We herein provide a narrative literature revision relative to hepatic disease occurrence in over or undernourished subjects, to shed light on the paradox where both sides of malnutrition lead to similar liver dysfunction and fat accumulation. METHODS: Medline, EMBASE, and Cochrane Library were searched for publications up to July 2020. Articles discussing the association between both chronic and acute liver pathology and malnutrition were evaluated together with studies reporting the dietary intake in subjects affected by malnutrition. RESULTS: The association between overnutrition and non-alcoholic fatty liver disease (NAFLD) is well recognized, as the beneficial effects of calorie restriction and very low carbohydrate diets. Conversely, the link between undernutrition and liver injury is more complex and less understood. In developing countries, early exposure to nutrient deficiency leads to marasmus and kwashiorkor, accompanied by fatty liver, whereas in developed countries anorexia nervosa is a more common form of undernutrition, associated with liver injury. Weight gain in undernutrition is associated with liver function improvement, whereas no study on the impact of macronutrient distribution is available. We hypothesized a role for very low carbohydrate diets in the management of undernutrition derived liver pathology, in addition to the established one in overnutrition-related NAFLD. CONCLUSIONS: Further studies are warranted to update the knowledge regarding undernutrition-related liver disease, and a specific interest should be paid to macronutrient distribution both in the context of refeeding and relative to its role in the development of hepatic complications of anorexia nervosa. LEVEL OF EVIDENCE: Narrative review, Level V.

The gastro-jejunal anastomosis site influences dumping syndrome and weight regain in patients with obesity undergoing Laparoscopic Roux-en-Y Gastric Bypass.

PURPOSE: 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. METHODS: 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. RESULTS: 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 < 0.0001). Excess weight loss was 77.59% and 94.13% in patients with AGJ and PGJ, respectively (p < 0.001). WR rate was 16% and 4% in the AGJ and PGJ population, respectively (p < 0.001). DS prevalence was 38% and 76% in the AGJ and the PGJ population, respectively (p < 0.0001). The site of anastomosis was identified as an independent predictor of DS (OR5.15; 95% CI 2.82-9.41; p < 0.0001) and WR (OR5.31; 95% CI 2.32-12.15; p < 0.0001). Obesity-related complications significantly improved after surgery independent of the anastomosis site. CONCLUSION: LRYGB is effective in determining long-term weight loss and improvement of complications. AGJ is associated with lower prevalence of DS but more frequent WR. The anastomosis site is a factor to be considered when performing LRYGB. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

The psychological impact of COVID-19 pandemic on patients included in a bariatric surgery program.

PURPOSE: The COVID-19 pandemic has radically impacted the world lifestyle. Epidemics are well-known to cause mental distress, and patients with a current or past history of obesity are at increased risk for the common presence of psychological comorbidities. This study investigates the psychological impact of the current pandemic in patients participating in a bariatric surgery program. METHODS: Patients were consecutively enrolled during the Italian lockdown among those waiting for bariatric surgery or attending a post-bariatric follow-up, and were asked to complete through an online platform the Depression Anxiety Stress Scales-21 and a self-assessment questionnaire of 22 items evaluating the resilience, change in eating behavior and emotional responses referring to the ongoing pandemic. RESULTS: 59% of the 434 enrolled subjects reported of being worried about the pandemic, and 63% specifically reported of being worried about their or their relatives' health. 37% and 56% felt lonelier and more bored, respectively. 66% was hungrier with increased frequency of snacking (55%) and 39% reported more impulse to eat. Noteworthy, 49% felt unable to follow a recommended diet. No difference in terms of psychological profile was recorded among pre and post-bariatric subjects. Logistic regression analysis on post-bariatric patients showed a relationship between snacking, hunger, eating impulsivity, and anxiety, stress, and/or depression symptoms. CONCLUSION: The pandemic led to increased psychological distress in patients with a current or past history of obesity, reducing quality of life and affecting dietary compliance. Targeted psychological support is warranted in times of increased stress for fragile subjects such as pre- and post-bariatric patients. LEVEL OF EVIDENCE: Level V: cross-sectional descriptive study.

Obesity and SARS-CoV-2: A population to safeguard.

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.

Incremental role of glycaemic variability over HbA1c in identifying type 2 diabetic patients with high platelet reactivity undergoing percutaneous coronary intervention.

BACKGROUND: Diabetic patients with on-treatment high platelet reactivity (HPR) show an increased risk of thrombotic events. Whether measuring glycated haemoglobin (HbA1c) levels and/or glycaemic variability (GV) may help identifying diabetic patients at higher risk deserving tailored antiplatelet and/or glucose lowering strategies is unknown. We aimed to investigate the relationship between GV, HbA1c levels and platelet reactivity in patients with type 2 diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI). METHODS: Platelet reactivity was measured in type 2 DM patients using VerifyNow P2Y12 assay. HPR was defined as P2Y12 Reaction Unit (PRU) > 240. GV was expressed through mean amplitude of glycaemic excursions (MAGE) and coefficient of variance (CV) by using the iPro™ continuous glucose recorder. RESULTS: Thirty-five patients (age 70 ± 9 years, 86% male, mean HbA1c 7.2 ± 1.0%) on clopidogrel therapy were enrolled. HbA1c was independently associated with HPR (OR 7.25, 95% CI 1.55-33.86, p = 0.012). Furthermore, when factored into the model, GV indexes provided independent (OR 1.094, 95% CI 1.007-1.188, p < 0.034) and additional (p < 0.001) diagnostic significance in identifying diabetic patients with HPR. CONCLUSIONS: Glyco-metabolic state significantly correlates with HPR in well-controlled type 2 DM patients on clopidogrel therapy. HbA1c identifies patients at higher thrombotic risk but the highest diagnostic accuracy is achieved by combining GV and HbA1c. Whether individualized antithrombotic and glucose-lowering therapies based on the assessment of these parameters may reduce the incidence of thrombotic events in patients undergoing PCI should be further investigated.

Calcium citrate: from biochemistry and physiology to clinical applications.

Adequate daily calcium intake should normally be achieved by dietary sources. Since low calcium diets are quite common in subjects that do not reach the recommended intake and particularly those at risk of fractures, calcium supplements may become necessary. Different forms of calcium salts are available, but products containing calcium citrate and calcium carbonate complexes are the most frequently used. Although only limited evidence on the efficacy and long-term safety of calcium citrate is available, these supplements may represent a valuable product for the management of different chronic pathological conditions. The aim of this review was to evaluate the current and potential clinical applications of calcium citrate. In particular, we focused on the use of calcium citrate supplementation in subjects with osteoporosis or in bariatric patients. Other pathological conditions that could benefit calcium citrate supplementation may include achloridria, chronic hypoparathyroidism and hypocitraturic subjects with moderate/high risk of nephrolithiasis. Indeed, citrate salts are widely used in the treatment of nephrolithiasis, since they have shown an inhibitory effect on kidney stone formation and recurrence.

Raman Spectroscopy Applied to Parathyroid Tissues: A New Diagnostic Tool to Discriminate Normal Tissue from Adenoma.

Primary hyperparathyroidism is an endocrine disorder characterized by autonomous production of parathyroid hormone. Patients with the symptomatic disease should be referred for parathyroidectomy. However, the distinction between the pathological condition and the benign one is very challenging in the surgical setting; therefore, accurate recognition is important to ensure success during minimally invasive surgery. At present, all intraoperative techniques significantly increase surgical time and, consequently, cost. In this proof-of-concept study, Raman microscopy was used to differentiate between healthy parathyroid tissue and parathyroid adenoma from 18 patients. The data showed different spectroscopic features for the two main tissue types of healthy and adenoma. Moreover, the parathyroid adenoma subtypes (chief cells and oxyphil cells) were characterized by their own Raman spectra. The partial least-squares discriminant analysis (PLS-DA) model built to discriminate healthy from adenomatous parathyroid tissue was able to correctly classify all samples in the calibration and validation data sets, providing 100% prediction accuracy. The PLS-DA model built to discriminate chief cell adenoma from oxyphil cell adenoma allowed us to correctly classify >99% of the spectra during calibration and cross-validation and to correctly predict 100% of oxyphil and 99.8% of chief cells in the external validation data set. The results clearly demonstrate the great potential of Raman spectroscopy. The final goal would be development of a Raman portable fiber probe device for intraoperative optical biopsy, both to improve the surgical success rate and reduce surgical cost.

Glycemic variability in the development of cardiovascular complications in diabetes.

Diabetes mellitus represents a major risk factor for the development of coronary artery disease and other vascular complications. Glycated haemoglobin, fructosamine, and fasting blood glucose levels are partial parameters to exhaustively describe patient dysglycemic status. Thus, recently the new concept of glycemic variability has emerged, including information about two major aspects: the magnitude of blood glucose excursions (from nadir to peak, thus lower and higher spikes) and the time intervals in which these fluctuations occur. Despite the lack of consensus regarding the most appropriate definition and tools for its assessment, glycemic variability seems to have more deleterious effects than sustained hyperglycemia in the pathogenesis of diabetic cardiovascular complications. This manuscript aimed to review the most recent evidence on glycemic variability and its potential use in everyday clinical practice to identify diabetic patients at higher risk of cardiovascular complications and thus needing stricter monitoring and treatment.

Radiofrequency ablation for the management of thyroid nodules: A critical appraisal of the literature.

The majority of benign thyroid nodules are asymptomatic, remain stable in size and do not require treatment. However, a minority of patients with growing nodules may have local symptoms or cosmetic concerns, and thus demand surgical therapy. The timely use of ultrasound-guided, minimally invasive thermal therapies has changed the natural history of benign, enlarging thyroid nodules (TNs). These procedures produce persistent shrinkage of TNs and an improvement of local symptoms. Among the various procedures, percutaneous ethanol injection represents the first-line treatment for thyroid cysts, while in solid cold nodules, laser and radiofrequency ablation (RFA) have proven to be very effective and safe techniques in producing significant volume reduction that remains stable over several years. In particular, RFA seems to be suited for the management of small and medium nodules, while larger nodules may require repeated RFA treatments, and could be difficult to treat if they extend into the chest. RFA is performed in outpatient clinics and has a lower risk of complications compared to surgery. However, to date, there is still no unanimous consensus on the percutaneous treatment of benign nodules using such minimally invasive thermal techniques. In this review, we critically revise the literature to identify patients who are more likely to benefit from RFA treatment as an alternative to surgery.

Pathophysiology of Bone Fragility in Patients with Diabetes.

It has been well established that bone fragility is one of the chronic complications of diabetes mellitus, and both type 1 and type 2 diabetes are risk factors for fragility fractures. Diabetes may negatively affect bone health by unbalancing several pathways: bone formation, bone resorption, collagen formation, inflammatory cytokine, muscular and incretin system, bone marrow adiposity and calcium metabolism. The purpose of this narrative review is to explore the current understanding of pathophysiological pathways underlying bone fragility in diabetics. In particular, the review will focus on the peculiar cellular and molecular system impairment that may lead to increased risk of fracture in type 1 and type 2 diabetes.

Irisin is associated with osteoporotic fractures independently of bone mineral density, body composition or daily physical activity.

BACKGROUND: Although there is an evidence of correlation between irisin and osteoporotic fractures, previous studies have not elucidated the relationship between irisin and either lean or fat mass. The main aim of this study is to investigate the relationship between irisin and body composition in postmenopausal women with osteoporosis and the impact of irisin levels on fragility vertebral fractures. METHODS: In this cross-sectional study, 36 overweight subjects affected by at least one vertebral osteoporotic fracture confirmed by an X-ray vertebral morphometry and 36 overweight nonosteoporotic subjects were enrolled. Serum irisin levels were measured using an irisin competitive ELISA. We evaluated lumbar spine and hip BMD and body composition using dual energy X-ray absorptiometry. To measure and monitor daily physical activity, each subject wore an armband for approximately 72 h. RESULTS: No significant correlations were found between irisin and BMD at any site and between irisin with either lean or fat mass. Serum levels of irisin were not correlated with the daily physical activity. Serum irisin levels were lower in subjects with previous osteoporotic fractures than in controls (P = 0·032), and the difference in irisin levels remained significant after adjustment for creatinine (P = 0·037), vitamin D (P = 0·046), lean mass (P = 0·02), lumbar BMD (P = 0·023) and femoral BMD (P = 0·032). CONCLUSION: Our data confirm an inverse correlation between irisin levels and vertebral fragility fractures, but no significant correlation was found with BMD or lean mass. Irisin may play a protective role on bone health independent of BMD but further studies are needed to clarify the relationship between irisin and bone metabolism.