Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial.

OBJECTIVES: Patients with type 2 diabetes (T2DM) are at increased fracture risk. Resveratrol has shown beneficial effects on bone health in few studies. The aim of this trial was to investigate the effects of resveratrol on bone mineral density (BMD) and on calcium metabolism biomarkers in T2DM patients. METHODS: In this double-blind randomized placebo-controlled trial 192 T2DM outpatients were randomized to receive resveratrol 500 mg/day (Resv500 arm), resveratrol 40 mg/day (Resv40 arm) or placebo for 6 months. BMD, bone mineral content (BMC), serum calcium, phosphorus, alkaline phosphatase, and 25-hydroxy vitamin D were measured at baseline and after 6 months. RESULTS: At follow-up, calcium concentrations increased in all patients, while within-group variations in alkaline phosphatase were higher in both resveratrol arms, and 25-hydroxy vitamin D increased in the Resv500 arm only, without between-group differences. Whole-body BMD significantly decreased in the placebo group, while whole-body BMC decreased in both the placebo and Resv40 arms. No significant changes in BMD and BMC values occurred in the Resv500 arm. The adjusted mean differences of change from baseline were significantly different in the Resv500 arm vs placebo for whole-body BMD (0.01 vs -0.03 g/cm2, p = 0.001), whole-body BMC (4.04 vs -58.8 g, p < 0.001), whole-body T-score (0.15 vs -0.26), and serum phosphorus (0.07 vs -0.01 µmol/L, p = 0.002). In subgroup analyses, in Resv500 treated-patients BMD values increased to higher levels in those with lower calcium and 25-hydroxy vitamin D values, and in alcohol drinkers. CONCLUSIONS: Supplementation with 500 mg resveratrol prevented bone density loss in patients with T2DM, in particular, in those with unfavorable conditions at baseline.

Effects of Self-Conditioning Techniques (Self-Hypnosis) in Promoting Weight Loss in Patients with Severe Obesity: A Randomized Controlled Trial.

OBJECTIVE: The usefulness of the rapid-induction techniques of hypnosis as an adjunctive weight-loss treatment has not been defined. This randomized controlled trial evaluated whether self-conditioning techniques (self-hypnosis) added to lifestyle interventions contributed to weight loss (primary outcome), changes in metabolic and inflammatory variables, and quality of life (QoL) improvement (secondary outcomes) in severe obesity. METHODS: Individuals (with BMI = 35-50 kg/m2 ) without organic or psychiatric comorbidity were randomly assigned to the intervention (n = 60) or control arm (n = 60). All received exercise and behavioral recommendations and individualized diets. The intervention consisted of three hypnosis sessions, during which self-hypnosis was taught to increase self-control before eating. Diet, exercise, satiety, QoL, anthropometric measurements, and blood variables were collected and measured at enrollment and at 1 year (trial end). RESULTS: A similar weight loss was observed in the intervention (-6.5 kg) and control (-5.6 kg) arms (ß = -0.45; 95% CI: -3.78 to 2.88; P = 0.79). However, habitual hypnosis users lost more weight (-9.6 kg; ß = -10.2; 95% CI: -14.2 to -6.18; P < 0.001) and greatly reduced their caloric intake (-682.5 kcal; ß = -643.6; 95% CI: -1064.0 to -223.2; P = 0.005) in linear regression models. At trial end, the intervention arm showed lower C-reactive protein values (ß = -2.55; 95% CI: -3.80 to -1.31; P < 0.001), higher satiety (ß = 19.2; 95% CI: 7.71-30.6; P = 0.001), and better QoL (ß = 0.09; 95% CI: 0.02-0.16; P = 0.01). CONCLUSIONS: Self-hypnosis was not associated with differences in weight change but was associated with improved satiety, QoL, and inflammation. Indeed, habitual hypnosis users showed a greater weight loss.

Different quality of treatment in retroperitoneal sarcomas (RPS) according to hospital-case volume and surgeon-case volume: a retrospective regional analysis in Italy.

BACKGROUND: Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV) or by Surgeon Case Volume (SCV). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the quality of surgery in a wide region of Northern Italy. METHODS: We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (< 100 sarcomas observed per year). RESULTS: Data regarding 138 patients were collected. Patients coming from LCV hospitals (66) were excluded from the analysis as prognostic data were frequently not available. Among the 72 remaining cases of HCV hospitals 60% of cases had R0/R1 margins, with a more favorable distribution of R0/R1 versus R2 in HVCCC compared to HVTCA. CONCLUSIONS: In HCV hospitals, sarcoma SCV may significantly influence RPS treatment quality. In low-volume centers surgical reports can often miss important prognostic issues and surgical quality is generally poor.

Timing of food intake: Sounding the alarm about metabolic impairments? A systematic review.

Growing evidence points to an association between timing of food intake and obesity in humans, raising the question if when to eat matters as much as what and how much to eat. Based on the new definition of obesity as a chronobiological disease, an unusual or late meal timing represent a circadian chronodisruption, leading to metabolic impairments. Preliminary data from cross-sectional and experimental studies suggest that changes in meal timing can influence obesity and success of weight loss therapy, independently from total energy intake, dietary composition and estimated energy expenditure. A systematic review of observational and experimental studies in humans was conducted to explore the link between time of food ingestion, obesity and metabolic alterations. Results confirm that eating time is relevant for obesity and metabolism: observational and experimental studies found an association between meal timing, weight gain, hyperglycemia and diabetes mellitus with benefits deriving from an early intake of food in the day in a wide range of individuals. Herein clinical, future perspectives of chronoprevention and chronotherapy of obesity and type 2 diabetes are also provided. In conclusion, meal timing appears as a new potential target in weight control strategies, and therapeutic strategies should consider this contributor in the prevention of obesity.

Sorafenib treatment of radioiodine-refractory advanced thyroid cancer in daily clinical practice: a cohort study from a single center.

Treatment options for recurrent or metastatic differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) are inadequate. Multitargeted kinase inhibitors have recently shown promising results in phase 2-3 studies. This retrospective study aimed to document our clinical experience on the effects of sorafenib in the setting of daily clinical practice. Retrospective study evaluating the efficacy and safety of sorafenib in a cohort of patients consecutively treated with sorafenib at a single center. Twenty patients with advanced RAI-refractory thyroid carcinoma were enrolled (March 2011-March 2014). Patients generally started with 400 mg of sorafenib twice daily, tapering the dose in case of side effects. Radiological response and toxicity were measured during follow-up, together with safety parameters. CT scans were performed by a single experienced radiologist every 3-4 months. Five patients stopped sorafenib within 90 days due to severe toxicities. Median progression-free survival was 248 days. Five patients had a partial response (PR), achieved in all cases within 3 months, whereas 5 had stable disease (SD) at 12 months. Durable response rate (PR plus SD) for at least 6 months was 50 %, among those who received sorafenib for at least 3 months. Commonest adverse events included skin toxicity, gastrointestinal and constitutional symptoms. In our cohort of patients with advanced RAI-refractory thyroid carcinoma, sorafenib confirmed antitumor activity leading to SD or PR in the majority of cases, at the expense of clinically relevant side effects. More effective and tolerable agents are still needed in the treatment of RAI-refractory DTC.

Prognostic role of vitamin d status and efficacy of vitamin D supplementation in cancer patients: a systematic review.

BACKGROUND: Whether or not hypovitaminosis D can influence the prognosis of cancer patients and whether or not vitamin D (vitD) supplementation improves outcome remain controversial. DESIGN: Studies evaluating the prognostic role of vitD and vitD receptor (VDR) in cancer patients and trials evaluating the efficacy of vitD administration on patient outcome were identified by a search of MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library through June 2010. RESULTS: Twenty-five studies were included. A negative prognostic role for low serum vitD level was observed in five cohort studies including patients with breast cancer (one study), colon cancer (two studies), prostate cancer (one study), and melanoma (one study), but not in two studies on non-small cell lung cancer and one study on breast cancer. Three of four studies showed that VDR(+) tumors carry a better prognosis than VDR(-) tumors, whereas VDR polymorphisms were significantly associated with prognosis in five of 10 studies. A significant interaction between serum vitD level and VDR polymorphism was observed in one study. Three randomized trials involving advanced prostate cancer patients explored the prognostic role of vitD supplementation. A meta-analysis of these trials showed no effect on survival (pooled risk ratio, 1.07; 95% confidence interval, CI, 0.93-1.23), with strong heterogeneity among studies. CONCLUSION: Hypovitaminosis D seems to be associated with a worse prognosis in some cancers, but vitD supplementation failed to demonstrate a benefit in prostate cancer patients. The currently available evidence is insufficient to recommend vitD supplementation in cancer patients in clinical practice.

Efficacy of antioxidant treatment in reducing resistin serum levels: a randomized study.

OBJECTIVES: Few in vitro studies have examined the participation of resistin, a recently discovered adipokine, in oxidative processes. We investigated whether in vivo treatment with the antioxidant vitamin C might affect resistin serum levels. DESIGN: Randomized prospective open trial. SETTING: San Giovanni Battista Hospital, Turin, Italy. PARTICIPANTS: Eighty healthy individuals. INTERVENTION: Administration of 2 g of ascorbic acid orally for 2 wk (n = 40; experimental group) or no supplementation (n = 40; control group). OUTCOME MEASURES: The primary end point was the between-group difference in the before-after change in resistin serum level after vitamin C supplementation. Secondary endpoints were the within- and between-group changes in glucose, insulin, lipid parameters, C-reactive protein fasting values, and markers of oxidative stress. RESULTS: In the experimental group, vitamin C supplementation was significantly associated with both resistin concentration reduction (from 4.3 +/- 1.5 to 2.9 +/- 0.8 ng/ml; 95% confidence interval [CI] -1.87, -1.03) and ascorbic acid level increase (from 9.4 +/- 2.9 to 19.0 +/- 5.2 mg/l; 95% CI 7.9, 11.2). In the control group, resistin levels did not change significantly (from 4.2 +/- 1.0 to 4.3 +/- 0.9 ng/ml; 95% CI -0.07, 0.37). The between-group differences were highly significant (p < 0.001). Vitamin C supplementation was also associated with a statistically significant reduction in nitrotyrosine level and incremental increase in reduced glutathione. In a linear regression model, within-individual changes in vitamin C concentrations were inversely correlated with changes in resistin levels in both groups (each unit increase of vitamin C corresponded to a decrease of about 0.10 units of resistin levels (95% CI 0.13, 0.08; p < 0.001). CONCLUSION: This is to our knowledge the first randomized trial in humans that has demonstrated that short-term vitamin C supplementation could significantly reduce resistin levels, independent of changes in inflammatory or metabolic variables. Future investigations of resistin participation in oxidative processes are warranted.

Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients.

BACKGROUND: Iron balance is critical for adequate erythropoiesis, but its optimal therapeutic regimen remains to be defined. Continuous maintenance therapy with iron has been proposed for dialysis patients on recombinant human erythropoietin (rHuEpo) in the hope that the regimen is adequate and safe. METHODS: We determined serum ferritin, transferrin, transferrin saturation (TSAT), serum transferrin receptors, albumin and C-reactive protein (CRP) in a 3-year prospective study in 30 chronic haemodialysis patients on dialysis treatment for 132+/-111 months (18 males, 12 females; mean age 56+/-14 years). Beginning in the year 2000, they regularly received low-dose maintenance iron supplementation (i.v. iron gluconate 31.25 mg/week) for 12 months (Period 1 or first treatment phase), followed by a 6-month withdrawal (Period 2 or stop phase) and then by continuous maintenance iron therapy (i.v. iron gluconate 31.25 mg/week) for another 9 months (Period 3 or re-challenge phase). RESULTS: A significant increase in serum ferritin and TSAT was observed, with values exceeding 500 ng/ml and 50% in 10/30 (33%) and 7/30 (23%) of subjects, respectively, in Period 1, and in 11 and 5% in Period 3. A significant decrease in serum transferrin was documented during Period 1, followed by an increase in Period 2 and a decrease in Period 3. Serum albumin remained stable. Serum transferrin was always negatively correlated with ferritin (r = -0.41, P<0.001) and weakly correlated with serum transferrin receptors (r = 0.178, P<0.05), but was not correlated with serum albumin or CRP. Regression equations based on pre-treatment serum ferritin values were developed for predicting the value of serum ferritin at any time following the beginning of continuous iron supplementation. They fitted a linear relationship for males (y = 81 + 21.5 x time) and for females (y = 65 + 22 x time). Percentile charts for quantitative tracking of serum ferritin increases and decreases in patients have also been developed from values measured at different times. These charts show box-plot distributions of expected ferritin against time. CONCLUSIONS: Even continuous low-dose maintenance iron therapy, with only 31.25 mg weekly over 1 year, cannot prevent the risk of iron overload in patients with moderate anaemia. Furthermore, this treatment is responsible for decreases in serum transferrin, unrelated to changes in serum albumin, possibly of concern for hypo-transferrinaemia as an independent risk factor for iron toxicity.