Long-Term Efficacy of Intensive Zoledronate Therapy and Predictors of Retreatment in Paget’s Disease of Bone

Despite the current debate on the best therapeutic approach, i.e. symptomatic vs intensive strategy, one zoledronate (Zol) infusion is effective in most patients with Paget’s disease of bone (PDB), whereas few need retreatment, whose predictors are not well established. We aimed to evaluate long-term efficacy of intensive Zol therapy and predictors of retreatment in PDB. Pagetic complications, clinical and biochemical response to Zol together with frequency of retreatment were retrospectively assessed in forty-seven PDB patients (age, mean ± SD: 72.5 ± 8.9 years, M/F: 24/23; symptomatic/asymptomatic: 16/31). Statistical analysis for retreatment prediction were based on Mann–Whitney U test, Pearson’s Χ2 and ROC curve analysis. During seven-year follow-up, all patients achieved pain relief and only one underwent arthroplasty. Bone alkaline phosphatase (BAP) detected three non-responder (6%) and six relapsing (13%) patients needing retreatment. Retreated patients had less old age (66.1 ± 11.2 vs 74.0 ± 7.7 years), higher frequency of polyostotic disease (78% vs 40%) and higher baseline (96.5 ± 24.8 vs 44.9 ± 27.7 mcg/l) and post-Zol nadir BAP levels (24.7 ± 24.1 vs 8.1 ± 4.1 mcg/l) than patients treated once (p < 0.05 for all comparisons). In multivariate analysis both serum baseline and post-Zol nadir BAP significantly predicted retreatment (OR 1.09, 95%CI 1.01–1.17 and 1.29, 1.03–1.62, respectively), with ROC curve analysis showing the greatest accuracies for threshold values of 75.6 and 9.9 mcg/l (sensitivity 88 and 90%, specificity 94 and 86%, AUC 0.92 and 0.93, respectively). Our data in mostly asymptomatic, metabolically active PDB patients treated with intensive Zol therapy show a negligible incidence of pagetic complications and long-term optimal disease control, with BAP being the best predictor of retreatment

Individual metering and submetering for cooling application

In 2012 the Energy Efficiency Directive (EED) has set mandatory installation of individual metering and submetering systems for accounting thermal energy consumption in buildings where centralized heating/cooling sources are present, when technically feasible and cost efficient. As a consequence, direct thermal energy meters or indirect heat accounting systems have spread widely in residential buildings, for metering and sub-metering in space heating applications. On the other hand, individual metering of thermal energy in space cooling is a difficult task, due to the very different types of cooling systems and to the lack of technical and legal metrology regulation. In this paper possible solutions available for direct metering and submetering of different types of centralized cooling systems are discussed. Indeed, for direct metering application, the cooling fluid flow metering is a particularly crucial issue due to small pipe diameters and different fluid properties. Thus, the authors carried out an experimental comparison between a Coriolis flow-meter and an ultrasonic clamp-on flow-meter in the cooling fluid circuit of a direct expansion system. Tests have been performed at different operative temperature differences between flow and return, showing relative errors within ± 10%

Expanded Total Equivalent Warming Impact analysis on experimental standalone fresh-food refrigerator

The stand-alone refrigerators for fresh food storage represent a large part of supermarket refrigeration equip-ment. In these devices, the usage of refrigerants with low Global Warming Potential allows the mitigation of the direct emissions due to refrigerant leakages. In contrast, the indirect emissions in these components are highly dependent on the refrigerant charge, leakage, and equivalent emission factors related to the electricity pro-duction mix. The most used index to evaluate the environmental impact of refrigerators is the Total Equivalent Warming Impact. Despite that this index presents limits on the fixed evaluation of many parameters such as refrigerant charge, electricity consumption and, electricity emission factor. Otherwise in this study, an accurate evaluation of refrigerators emissions has been realised by using the innovative Expanded Total Equivalent Warming Impact method to an experimental stand-alone refrigerator by using a dynamic approach to evaluate direct and indirect contributions. The environmental analysis considers four different refrigerants and four different countries of location. The results show that the indirect emissions due to electricity consumption cover the highest share of emissions. In addition, the operating years affected by low refrigerant charges are respon-sible for emissions by greater than 25% compared to other ones. The hourly equivalent emissions due to elec-tricity consumption in countries characterized by an electricity generation mix mainly based on renewable and/ or nuclear plants show an indirect environmental impact up to 5 times lower than countries with a natural gas -based electricity production mix. The study also defines new strategies to reduce the environmental impact of the stand-alone refrigerator such as the use of photovoltaic systems combined with this technology or earlier maintenance processes that could determine an equivalent emission saving of up to 38%

Effects of intensive lifestyle changes on erectile dysfunction in men

Introduction. Limited data are available supporting the notion that treatment of lifestyle risk factors may improve erectile dysfunction (ED). Aim. In the present study, we analyzed the effect of a program ofchanging in lifestyle designed to improve erectile function in subjects with ED or at increasing risk for ED. Methods. Men were identified in our database of subjects participating in randomized controlled trials evaluating the effect of lifestyle changes. A total of 209 subjects were randomly assigned to one of the two treatment groups. The 104 men randomly assigned to the intervention program received detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity. The 105 subjects in the control group were given general information about healthy food choices and general guidance on increasing their level of physical activity. Main Outcome Measures. Changes in erectile function score (International Index of Erectile Function-5 [IIEF-5]; items 5, 15, 4, 2, and 7 from the full-scale IIEF-15) and dependence of the restoration of erectile function on the changes in lifestyle that were achieved. Results. Erectile function score improved in the intervention group. At baseline, 35 subjects in the intervention group and 38 subjects in the control group had normal erectile function (34% and 36%, respectively). After 2 years, these figures were 58 subjects in the intervention group and 40 subjects in the control group, respectively (56% and 38%, P = 0.015). There was a strong correlation between the success score and restoration of erectile function. Conclusions. It is possible to achieve an improvement of erectile function in men at risk by means of nonpharmacological intervention aiming at weight loss and increasing physical activity. © 2009 International Society for Sexual Medicine

Obesity in Prader–Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches

Prader–Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management

Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia

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Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401

Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients

Case Report: Post-gastrectomy reactive hyperinsulinemic hypoglicaemia: glucose trends before and after canagliflozin treatment

The pathogenesis of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia is not yet fully clarified. Recent studies suggest an up-regulation of the intestinal glucose transporter SGLT-1 aimed to prevent carbohydrate malabsorption. The overexpression of SGLT-1 could therefore represents one of the mechanisms underlying the wide glycemic excursions found in patients after gastrectomy, but studies investigating the use of SGLT-1/SGLT-2 inhibitors in patients with post-gastrectomy reactive hyperinsulinemic hypoglycaemia are very scant in the literature. We report the case of a 37-year-old non diabetic man who frequently presented symptoms of hypoglycaemia in the postprandial period. In 2012, he underwent Roux en-Y gastric bypass (RYGB) and after two years, he started to experience typical symptoms of reactive hyperinsulinaemic hypoglycaemia. We suggested healthy modifications of dietary habits and periodic follow-up visits with a dietitian. After three months, the patient still presented symptoms of reactive hypoglycaemia; we provided him with Flash Glucose Monitoring (FGM) to assess trend of glucose levels in interstitial fluid during the day and we decided to introduce canagliflozin 300 mg/day before the main meal. Hypoglycaemic events previously referred by the patient and clearly recorded by FGM completely disappeared taking canagliflozin. We found a reduction of time spent in hypoglycaemia, an improvement of glycemic variability and an increase of time in target range. It was also noted a reduction of time spent in hyperglicemia with consequent improvement of average glucose values and of glucose main indicator. This is the first report with FGM supporting a role of canagliflozin in the management of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia. Our preliminary results are very limited but in line with those of the literature and showed for the first time a reduction of hypoglycaemic events and an improvement of glycemic variability through a flash glucose monitoring system. Further studies are mandatory to confirm this therapeutic opportunity