Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

Ultrasound-guided laser ablation of very large benign thyroid nodules: 4-year, retrospective follow-up in 24 patients.

BACKGROUND: Percutaneous, ultrasound-guided laser ablation is a proven management approach for the treatment of Benign Thyroid Nodules (BTN), but only sporadic cases of treatment of large-volume nodules with laser ablation have been reported. The aim of this study was to evaluate the efficacy and safety of laser ablation in the treatment of very large (> 100 mL) thyroid nodules. METHODS: Between 2009 and 2016, 24 patients with very large, BTN received 2-3 sessions of laser ablation over the course of 12 months. Nodule volume was measured before treatment, and at 1 and 4 years. RESULTS: Prior to treatment, median nodule volume was 138 mL (range: 102-289 mL). At 1 year, technique efficacy was achieved in 75% of patients, with median nodule volume significantly reduced to 26 mL (range: 15-31 mL, p < 0.001 vs pretreatment). Volume reduction ratio (VRR) at 1 year was 81%. At 4-year follow-up, median nodule volume was 27 mL (range: 15-33 mL, p < 0.001 vs pretreatment), with a VRR of 80%. Two patients had nodule regrowth > 50% and went to surgery - one patient after 1 year and the other after 3 years. Treatment was well tolerated; there were no major complications, although transient fever occurred in 12% (3/24) of patients and mild-to-moderate pain was experienced by 8% (2/24) of patients. CONCLUSIONS: In this patient series, percutaneous, ultrasound-guided laser ablation of very large thyroid modules provided long-term benefits and the treatment was well tolerated.

Physical Activity Modulates the Overexpression of the Inflammatory miR-146a-5p in Obese Patients.

Specific microRNAs (miRs), including the "angio-miR-126" and the "inflamma-miR-146a-5p," have been proposed as biomarkers and even therapeutic targets of obesity-associated metabolic diseases. Physical activity, a key measure of prevention for obesity and its complications, is reported to influence the expression of these miRs. In this study, we investigate whether a physical activity program proven to improve metabolic parameters in obese patients can correct the circulating levels of these miRs. Plasma miR-126 and miR-146a-5p were measured in a cohort of obese patients (n = 31, 16F + 15M) before and after the 3-month physical activity program of the CURIAMO trial (registration number for clinical trials: ACTRN12611000255987) and in 37 lean controls (24F + 13M). miR-146a-5p, but not miR-126, was significantly increased in obese patients as compared with lean controls and decreased in approximately two-thirds of the participants post-intervention with a response that positively correlated with pre-intervention levels of this miR. Waist circumference, the inflammatory cytokine IL-8 and lipid parameters, principally total cholesterol, showed the strongest correlation with both the baseline levels and post-intervention correction of miR-146a-5p. Post-hoc analysis of experimental data supports the use of miR-146a-5p as a biomarker and predictor of the clinical response to physical activity in obese patients. Furthermore, miR-146a-5p expression was confirmed to increase together with that of the inflammatory genes TLR4, NF-κB, IL-6, and TNF-α in LPS-stimulated human mononuclear leukocytes. In conclusion, the inflamma-miR-146a-5p can serve as a personalized predictor of clinical outcome in obese patients entering physical activity weight-reduction programs. © 2018 IUBMB Life, 70(10):1012-1022, 2018.

A single session of laser ablation for toxic thyroid nodules: three-year follow-up results.

PURPOSE: To confirm the effectiveness of laser ablation on toxic nodules in a large population with three years of follow-up. MATERIAL AND METHODS: Between 2009 and 2014, we treated 82 patients with hyperthyroidism related to the presence of a toxic nodular goitre. Patients were pre-treated pharmacologically with methimazole prior to single session of laser ablation (LA) and then followed up every 3 months with FT4 and TSH blood tests as well as ultrasound examination of the nodules treated. RESULTS: All patients responded to the treatment. The median nodule volume decreased from 12 ml (range 5-118 ml) to 5 ml (range 1.2-40 ml) after three years (p < 0.001). The percentage of patients who discontinued methimazole therapy was reduced by increasing the initial volume of the toxic nodule. In nodules with a volume less than 5 ml, all patients were able to suspend methimazole; this percentage was reduced to 90.2% in nodules with a volume between 5 and 15 ml, 61.1% in those with volume 15-25 ml and only 28.5% in nodules larger than 25 ml. We had no major complications but only moderate pain and fever in the evening, a few hours after ablation therapy in 10% of treated patients. CONCLUSIONS: Single session of LA of toxic thyroid nodules is effective and safe, especially in nodules with a volume under 15 ml.

A comparison of laser with radiofrequency ablation for the treatment of benign thyroid nodules: a propensity score matching analysis.

PURPOSE: To compare technique efficacy and safety of laser ablation (LA) and radiofrequency ablation (RFA) in treatment of benign thyroid nodules. MATERIALS AND METHODS: Institutional review board approval was obtained, and patients' consent was waived. 601 nodules were treated from May 2009 to December 2014 at eight centres, 449 (309 females, age 57 ± 14 years) with LA and 152 (107 females, age 57 ± 14 years) with RFA. A matched cohort composed of 138 patients from each group was selected after adjustment with propensity score matching. Factors influencing volume reduction at 6 and 12 months and complications were evaluated. RESULTS: No significant differences were observed in the baseline characteristics between groups after propensity score matching adjustment. Mean nodule reduction at 6 and 12 months was -67 ± 19% vs. -57 ± 21% (p < 0.001) - 70 ± 19% vs. -62 ± 22% (p = 0.001) in LA group and in RFA group, respectively. Nodules with volume >30 mL had significantly higher percentage volume reduction at 6 and 12 months (-69 ± 19 vs. -50 ± 21, p = 0.001) and (-73 ± 18 vs. -54 ± 23 8, p = 0.001) in the LA group than in the RFA group, respectively. In both groups, operator's skills affected the results. Major complications occurred in 4 cases in each group (p = 0.116) Conclusions: LA and RFA showed nearly similar outcome but LA was slightly more effective than RFA in large nodules. Operator's skills could be crucial in determining the extent of nodule volume reduction regardless of the used technique.

Thyroid nodule morphology affects the efficacy of ultrasound-guided interstitial laser ablation: a nested case-control study.

PURPOSE: The literature reports a wide range of percentages of ablation in the treatment of thyroid nodules. The aim of this nested case-control study was to evaluate whether the different morphological (well-defined vs. agglomerate) characteristics of nodules affect the success rate. MATERIALS AND METHODS: We selected 20 patients with a single and /or dominant well-defined nodule (group 1) and 20 with a nodular formation resulting from the fusion of multiple nodules (group 2). All the nodules were treated by the laser method receiving the same energy. RESULTS: At 6 months, patients in group 1 showed a greater decrease in volume than those in group 2. These differences were more evident after 12 months. CONCLUSIONS: Our study demonstrates that the efficacy of laser treatment can be predicted by nodule morphology and contributes to explaining the wide differences in the percentages of ablation reported in literature.

A time-lagged, actor-partner interdependence analysis of alliance to the group as a whole and group member outcome in overweight and obesity treatment groups.

A time-lagged design was used to examine how the perceptions of alliance to the group as a whole by the other group members at an earlier point in the group were related to an individual group member's perceptions of alliance to the group as a whole at a later point in the group. We also examined how treatment outcome moderated this relationship. Seventy-three patients diagnosed as overweight or obese participating in 10 short-term therapy groups provided data for analyses. Group members completed measures of cohesion to the group and alliance to the group as a whole at the third, sixth, and last session of 12-session groups as well as pre- and posttest ratings on Obesity-Related Well-Being and the Outcome Questionnaire-45. As hypothesized, earlier ratings of alliance to the group as a whole by the other group members were related to later ratings of alliance to the group as a whole by the group member. Also as hypothesized, when group members had a better outcome, there was a significant positive relationship between perceptions of alliance to the group as a whole by the other group members at an earlier point in the group and an individual group member's perceptions of alliance to the group as a whole at a later point in time. When members had a worse outcome, there was no relationship between perceptions of alliance to the group as a whole by the other group members at an earlier point in the group and an individual group member's perceptions of alliance to the group as a whole at a later point in the group.

Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

The administration of anesthetic in the thyroid pericapsular region increases the possibility of side effects during percutaneous laser photocoagulation of thyroid nodules.

BACKGROUND AND OBJECTIVE: Nodular thyroid disease is very frequent in iodine-deficient areas affecting at least 50% of the population. Percutaneous laser ablation (LA) represents an effective method and an alternative to conventional surgery. Since the first description of the LA methodology for thyroid nodules, various studies have suggested some modifications to increase the percentage of volume reduction of the nodules. One of these alternatives involves the injection of anesthetic in the pericapsular thyroid space with detachment of the capsule itself from the surrounding tissue. The aim of this study was to retrospectively evaluate whether using local anesthetic during LA is more effective in reducing volume size of treated nodules, and whether it causes fewer side effects than using no local anesthesia. STUDY DESIGN: A retrospective analysis was conducted on 100 LA procedures performed on 100 patients between January 2009 and December 2011. The patients were divided into two groups: Group A (n = 50) received Lidocaine around the capsule of the thyroid nodule and Group B (n = 50) did not receive any local anesthetic treatment. Before treatment, the median volume size of the nodules of the two groups was similar. RESULTS AND CONCLUSIONS: The results of our study demonstrate that the injection of local anesthetic does not help reduce nodule volume and that side effects (fever and pain) increase about threefold in the early hours following LA treatment. Thus, we do not recommend local anesthesia before LA of thyroid nodules.

Ultrasound-guided interstitial laser ablation for thyroid nodules is effective only at high total amounts of energy: results from a three-year pilot study.

OBJECTIVE: According to cross-sectional surveys, the prevalence of nontoxic nodular goiter appears to be higher in the adult population. Surgical intervention is indicated for the following: (a) progressive goiter growth, (b) compression of organs such as the trachea and esophagus, and (c) significant aesthetic disfigurement. Ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules is a viable alternative to traditional surgery. However, studies that have appeared in literature since the introduction of ultrasound-guided laser photocoagulation for the treatment of benign thyroid nodules report contradictory data concerning the energy required for nodule ablation. The aim of the present trial was to evaluate retrospectively the efficacy of percutaneous laser thermal ablation in 2 groups of patients, one treated with low, and the other with high, total amount of energy. DESIGN: Forty euthyroid patients were treated with 1 session of percutaneous laser photocoagulation treatment at low (median = 71 J/mL; 20 patients) and high (median = 578 J/mL; 20 patients) energy. The volume of the nodules was measured by the same investigator, blinded for treatment, using the ellipsoid formula before treatment, at 2, 4, 8, and 30 weeks, and every 6 months for 3 years thereafter. RESULTS: Thyroid nodule ablation is effective over time only if a sufficient amount of energy (>400-500 J/mL for the nodular tissue to be treated) is given, although it incurs proportionate side effects. CONCLUSIONS: Percutaneous laser thermal ablation is a viable alternative to traditional surgery for the treatment of benign nodular thyroid disease only if a sufficient amount of energy is delivered.

Effects of a multidisciplinary lifestyle intervention for obesity on mental and physical components of quality of life: the mediatory role of depression.

The current study investigates the effects of a multidisciplinary lifestyle intervention for obesity on Health Related Quality of Life (HRQoL). In this study, 92 adults with obesity were weighed and completed the Short Form Health Survey (SF-36) and the Center for Epidemiologic Studies Depression Scale (CES-D) at the baseline and at the end of a 3-month intervention. Repeated measures analysis of variance (ANOVA), a series of hierarchical regressions, and the statistical mediation analysis of Baron and Kenny were conducted. (a) Over 3 months, changes in weight and the mental and physical scales of the SF-36 and depression were all significant. (b) The results indicate a significant mediation of changes in depression scores for the association between weight loss and enhancement on the General Health scale of the SF-36. Improvements to HRQoL from a multidisciplinary lifestyle intervention seem to affect both the physical and mental components of the SF-36 score and to reduce depression, contributing to enhanced self-perceptions of well-being.

Percutaneous Ultrasound-Guided Laser Ablation of Benign Thyroid Nodules: Results of 10-Year Follow-Up in 171 Patients.

CONTEXT: Percutaneous, ultrasound-guided laser ablation is effective in nodular thyroid disease. OBJECTIVE: The aim of this study was to evaluate the long-term (10-year) efficacy and safety of laser ablation in the treatment of benign thyroid nodules. METHODS: From 2009 to 2010, 171 patients received a single session of laser ablation. Evaluation of nodule volume was performed before treatment, at 6 months, and every year. RESULTS: Technique efficacy was achieved in 92% of patients at 1 year. Median nodule volume significantly decreased from 16.7 mL (range, 11.0-97.0 mL) at baseline to 5.0 mL (range, 4.1-32.0 mL) at 1 year, a volume reduction ratio (VRR) of 68%. The benefit of the treatment was durable (P < 0.001 vs baseline at all timepoints), with a VRR of 59% after 10 years. No cases of nodule regrowth > 50% were observed at 1 year, although such cases did occur after 4 years (n = 3; 1.7% of the overall cohort) and 7 years (n = 8; 4.7%). There were no further cases of regrowth beyond 7 years. When patients were stratified according to baseline nodule volume (< 15 mL, 15-25 mL, or > 25 mL), durable results were observed across all 3 categories, with the largest, most prolonged effect observed in patients with nodules < 15 mL. Treatment was well tolerated, with only minor, transient complications of fever and local pain, and 98% of patients willing to recommend the treatment. CONCLUSION: Percutaneous, ultrasound-guided laser ablation of benign thyroid nodules provides long-term benefits and the treatment is well tolerated.

Surgical treatment of primitive thyroid lymphoma.

AIMS AND BACKGROUND: Primitive thyroid lymphoma, although rare, is becoming more frequent. Its incidence is increasing, from 0.5% in the sixties to 1-5% of all thyroid neoplasms today. The diagnosis of such neoplasms is not always straightforward. In fact, it is often the result of pathologic findings on a gland resected for an apparently benign disease. Surgical dissection may prove more complicated than in standard cases of thyroidectomy for the possible tight adhesions existing between the gland's capsule and the surrounding structures. In cases of capsular infiltration, postoperative external local radiotherapy is indicated. METHODS: A retrospective observational analysis was performed to establish whether patients with incidental thyroid lymphomas who underwent total thyroidectomy for another pathology had major surgical complications and worse prognostic results than patients with an accurate preoperative diagnosis. RESULTS: Six cases of thyroid lymphoma were retrospectively reviewed: 4 diffuse large B-cell lymphomas and 2 MALT lymphomas. Of these, 2 were correctly preoperatively identified by fine-needle aspiration biopsy and 4 were an unexpected finding at histology: 3 cases of total thyroidectomy carried out for huge hypothyroid goiter in patients affected by Hashimoto's thyroiditis and in 1 case of total thyroidectomy carried out for anaplastic carcinoma in a patient affected by Hashimoto's thyroiditis. CONCLUSIONS: In our experience, a correct preoperative diagnosis was extremely difficult (33%). In patients who underwent fine-needle aspiration, a correct diagnosis was made in 66% of cases. All patients with stage IE lymphoma who underwent total thyroidectomy had equivalent surgical complications and prognosis.

Combined aerobic and resistance training improves microcirculation in metabolic syndrome.

BACKGROUND: Exercise intervention improves macrovascular function in metabolic syndrome (MeS) patients, but few studies have evaluated the effect of exercise on microcirculatory dysfunction, which plays a key role in the development of MeS and its correlated organ damage. We carried out this intervention study to evaluate the influence of an aerobic and resistance training on skin microvascular reactivity in MeS patients. METHODS: Postocclusive reactive hyperemia (PORH) of the forearm skin was evaluated, by laser-Doppler flowmetry, before and after a 12-week program of aerobic and resistance training in 15 MeS patients referring to our Lipid Metabolism Outpatients Clinic, together with anthropometric, fitness and metabolic parameters; 15 matched MeS patients who did not exercise, served as a control group. The exercise training consisted of 2 sessions/week of aerobic and resistant exercise. RESULTS: Following exercise program, we observed a significant reduction in body weight, fat mass, fasting blood glucose, serum HbA1c and triglycerides, while HDL-cholesterol significantly increased. The exercise-treated group experienced a significant improvement in the area of hyperemia (AH) after PORH, and in all fitness parameters: VO2max, strength on the pulldown lat machine, chest press, leg press and leg extension. A significant correlation emerged between the increase in AH and the reduction in HbA1c and between increase in AH and strength at the chest press, and at the leg extension. CONCLUSIONS: Our study showed that a short-term combined aerobic-resistance training positively affects microvascular reactivity in MeS patients. This improvement is correlated with the reduction of HbA1c and fitness parameters, and particularly with increased muscle strength at the upper and lower limbs.

Effect of Short Term Intensive Lifestyle Intervention on Hepatic Steatosis Indexes in Adults with Obesity and/or Type 2 Diabetes.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has an estimated prevalence of 20-30% in the general population and even higher in individuals with metabolic risk factors. The aim of this study was to evaluate the effect of a lifestyle intervention program on surrogate markers of hepatic steatosis in obesity and/or type 2 diabetes patients, enrolled in the C.U.R.I.A.Mo. (Centro Universitario di Ricerca Interdipartimentale Attività Motoria) trial. METHODS: 102 subjects (56 females and 46 males, aged between 23 and 78) with type 2 diabetes, obesity or a BMI of at least 25 kg/m2 with comorbidities, participated in the intensive phase of a multidisciplinary lifestyle intervention program at the Healthy Lifestyle Institute of the University of Perugia (C.U.R.I.A.Mo.). Six indices related to NAFLD (Visceral Adiposity Index, Fatty Liver index, Non-Alcoholic Fatty Liver Disease liver fat score and liver fat equation, hepatic steatosis index and TyG index) were calculated before and after a three-month multidisciplinary lifestyle intervention. RESULTS: The intervention improved the anthropometric and clinical parameters in the total population, the obese and/or diabetics. Data showed a significant weight loss, a reduced waist circumference, triglycerides, and an improvement in Mediterranean diet adherence. Hepatic steatosis indices were significantly reduced in the total population and in different subgroups (males, females, obesity and diabetes).

An intensive lifestyle intervention reduces circulating oxidised low-density lipoprotein and increases human paraoxonase activity in obese subjects.

OBJECTIVE: Obesity has a great impact on cardiovascular morbidity and mortality, the treatment of this pathological state is important given the significant health consequences. Lifestyle and behaviour changes play a significant role in weight management. The purpose of this study was to investigate the impact of an intensive multidisciplinary lifestyle intervention on well-known atherogenic factors in a group of overweight and obese subjects. METHODS: A total of 44 people with overweight/obesity underwent a lifestyle intervention based on nutritional education, psychological support and a 3-month exercise training program with a frequency of twice a week. Several anthropometric and biochemical parameters were measured before and after the lifestyle intervention. RESULTS: Lifestyle intervention led to a significant reduction in metabolic profile including body mass index (BMI), waist circumference, systolic and diastolic blood pressure, plasma glucose, and plasma triglycerides. These reductions were also accompanied by a significant increase in maximal oxygen consumption and muscle strength. Furthermore, paraoxonase and lactonase activities and the concentration of Apoliproteins A1 (APO A1) were significantly increased and the serum levels of oxLDL reduced without any changes in the circulating levels of LDL and HDL. CONCLUSION: In conclusion, our study suggests that an intensive lifestyle intervention in obese subjects promotes a series of beneficial antiatherogenic changes which included increased enzyme activites of paraoxonase and lactonase, concentration of Apoliproteins A1 and decreased circulating levels of oxLDL.

Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome.

CONTEXT: To date, the metabolic effects of the long-term metformin administration in anovulatory patients with polycystic ovary syndrome (PCOS) are known, whereas few data are available on the effects of its suspension. OBJECTIVE: The objective of the study was to evaluate the effects of metformin suspension on insulin sensitivity in PCOS patients. DESIGN: This was a prospective, randomized, placebo-controlled study. SETTING: The study was conducted at the University "Magna Graecia" of Catanzaro, Italy. PATIENTS: Patients included 30 normal-weight anovulatory PCOS women and 10 age- and body mass index-matched healthy controls. INTERVENTION: PCOS patients were randomized to receive 1700 mg daily metformin (metformin group) or placebo tables (placebo group) for 12 months, whereas no treatment was administered in healthy women (control group). MAIN OUTCOME MEASURES: Clinical, endocrine, and metabolic profile and clamp insulin sensitivity index were evaluated at study entry and after 6, 12, 18, and 24 months. RESULTS: At baseline, the clamp insulin sensitivity index resulted significantly different (P < 0.05) in PCOS patients in comparison with healthy controls, without difference between metformin and placebo groups. During treatment, the clamp insulin sensitivity index was significantly improved (P < 0.05) in the metformin group in comparison with baseline and placebo group, without significant differences between the 6- and 12-month assessments. At 6 and 12 months after treatment suspension, in the metformin group, insulin sensitivity index significantly (P < 0.05) worsened in comparison with that observed at baseline and during treatment and with that observed in the placebo and control groups. CONCLUSION: In normal-weight anovulatory PCOS patients, long-term metformin administration exerts beneficial effects on peripheral insulin sensitivity. Furthermore, this effect disappears at treatment suspension.

Fine needle aspiration coupled with real-time PCR: a painless methodology to study adaptive functional changes in skeletal muscle.

BACKGROUND AND AIM: In this study we developed a new methodology for obtaining human skeletal muscle samples to evaluate gene expression. This approach is based on a fine needle aspiration technique, which allows us to extract a small tissue sample in a significantly less invasive manner than with classic biopsy. METHODS AND RESULTS: Multiplex tandem RT-PCR was used to determine the mRNA levels of genes involved in ATP production and mitochondrial biogenesis in muscle tissue. Samples of vastus lateralis muscle were obtained from 21 healthy subjects with different fitness levels. The principal findings in our study show a strong correlation between PGC-1alpha and COX5B (p<0.001) and between PGC-1alpha and MT-CO2 (p=0.017) expression. Furthermore, a significant positive correlation between mtDNA content and the percentage of MHCI present in the aspired samples were found (p=0.028). These data are in agreement with current knowledge on skeletal muscle physiology and show the reliability of the proposed method. CONCLUSION: This painless methodology can be used to investigate, in vivo, human muscle RNA and DNA adaptations in response to either physiological and/or pharmacological stimuli. This method has major clinical relevance, such as its application in clarifying the mechanisms underling metabolic and systemic disorders.

Effects of an Intensive Lifestyle Intervention to Treat Overweight/Obese Children and Adolescents.

OBJECTIVE: The purpose of the present study is to examine the effects of a multidisciplinary lifestyle intervention to treat overweight/obese children and adolescents. The main outcome was cardiometabolic risk based on the waist-to-height ratio (WHTR) measurement. Secondary outcomes were (1) changes in body composition; (2) adherence to a Mediterranean diet; and (3) physical performance. METHOD: The study involved 74 overweight/obese children or adolescents. The intervention was multidisciplinary including nutrition, exercise, and psychological aspects based on a family-based approach; it was delivered for six months for children and three months for adolescents. Before and after the intervention, several anthropometric measures (height, body weight, body mass index or BMI, waist circumference, and body composition), cardiometabolic risk index (waist-to-height ratio or WHTR), and nutrition habits of the participants and their families were evaluated. In addition, a set of functional motor fitness tests was performed to evaluate physical performance measures. RESULTS: After the intervention both children and adolescents showed a significant reduction in body weight, BMI, waist circumference, fat mass, and WHTR index and an improvement of fat-free mass, adherence to the Mediterranean diet, and physical fitness performance. CONCLUSION: A family-based multidisciplinary approach is effective in the short term in ameliorating the health status, the nutrition habits, and physical performance in children and adolescents.

Exercise and diabetes.

Physical activity activates has acute and chronic effects on glucose, lipid and protein metabolism. In type 1 diabetic subjects, the lack of the physiological inhibition of insulin secretion during exercise results in a potential risk of hypoglycemia. On the other hand, exercise-induced activation of counterregulatory hormones might trigger an acute metabolic derangement in severe insulin-deficient subjects. Thus, diabetic patients, before starting exercise sessions, must be carefully educated about the consequences of physical activity on their blood glucose and the appropriate modifications of diet and insulin therapy. Long-term effects of regular exercise are particularly advantageous for type 2 diabetic patients. Regular aerobic exercise reduces of visceral fat mass and body weight without decreasing lean body mass, ameliorates insulin sensitivity, glucose and blood pressure control, lipid profile and reduces the cardiovascular risk. For these reasons, regular aerobic physical activity must be considered an essential component of the cure of type 2 diabetes mellitus. In this regard, individual behavioral strategies have been documented to be effective in motivating sedentary type 2 diabetic subjects to the adoption and the maintenance of regular physical activity.