Differential effects of iron chelators on iron burden and long-term morbidity and mortality outcomes in a large cohort of transfusion-dependent β-thalassemia patients who remained on the same monotherapy over 10 years

We conducted a retrospective cohort study on 663 transfusion-dependent β-thalassemia patients receiving the same iron chelation monotherapy with deferoxamine, deferiprone, or deferasirox for up to 10 years (median age 31.8 years, 49.9 % females). Patients on all three iron chelators had a steady and significant decline in serum ferritin over the 10 years (median deferoxamine: -170.7 ng/mL, P = 0.049, deferiprone: -236.7 ng/mL, P = 0.001; deferasirox: -323.7 ng/mL, P < 0.001) yet had no significant change in liver iron concentration or cardiac T2*; while noting that patients generally had low hepatic and cardiac iron levels at study start. Median absolute, relative, and normalized changes were generally comparable between the three iron chelators. Patients receiving deferasirox had the highest morbidity and mortality-free survival probability among the three chelators, although the difference was only statistically significant when compared with deferoxamine (P = 0.037). On multivariate Cox regression analysis, there was no significant association between iron chelator type and the composite outcome of morbidity or mortality. In a real-world setting, there is comparable long-term iron chelation effectiveness between the three available iron chelators for patients with mild-to-moderate iron overload

Revisiting iron overload status and change thresholds as predictors of mortality in transfusion-dependent β-thalassemia: a 10-year cohort study

Data on iron overload status and change thresholds that can predict mortality in patients with transfusion-dependent β-thalassemia (TDT) are limited. This was a retrospective cohort study of 912 TDT patients followed for up to 10 years at treatment centers in Italy (median age 32 years, 51.6% female). The crude mortality rate was 2.9%. Following best-predictive threshold identification through receiver operating characteristic curve analyses, data from multivariate Cox-regression models showed that patients with Period Average Serum Ferritin (SF) > 2145 vs ≤ 2145 ng/mL were 7.1-fold (P < 0.001) or with Absolute Change SF > 1330 vs ≤ 1330 ng/mL increase were 21.5-fold (P < 0.001) more likely to die from any cause. Patients with Period Average Liver Iron Concentration (LIC) > 8 vs ≤ 8 mg/g were 20.2-fold (P < 0.001) or with Absolute Change LIC > 1.4 vs ≤ 1.4 mg/g increase were 27.6-fold (P < 0.001) more likely to die from any cause. Patients with Index (first) cardiac T2* (cT2*) < 27 vs ≥ 27 ms were 8.6-fold (P < 0.001) more likely to die from any cause. Similarly, results at varying thresholds were identified for death from cardiovascular disease. These findings should support decisions on iron chelation therapy by establishing treatment targets, including safe iron levels and clinically meaningful changes over time

A moderate 500-m treadmill walk for estimating peak oxygen uptake in men with NYHA class I-II heart failure and reduced left ventricular ejection fraction

Background: Maximal cardiopulmonary exercise testing (CPX) is the gold-standard for cardiorespiratory fitness assessment in chronic heart failure (CHF) patients. However, high costs, required medical supervision, and safety concerns make maximal exercise testing impractical for evaluating mobility-impaired adults. Thus, several submaximal walking protocols have been developed and currently used to estimate peak oxygen consumption (VO(2)peak)in CHF patients. However, these tests have to be performed at close to maximum exercise intensity. The aim of this study was to examine the validity of a 500-m treadmill-walking test carried out at moderate intensity for estimating VO(2)peak in community-dwelling adult and elderly patients with CHF and reduced left ventricular ejection fraction (HFrEF).Methods: Forty-three clinically stable men with HFrEF (age 67.7 +/- 9.2 years, and left ventricular ejection fraction, LVEF 38% +/- 6%) underwent exercise testing during an outpatient cardiac rehabilitation/secondary prevention program. Each patients completed a CPX, and a moderate and self-paced (11-13/20 on the Borg scale) 500-m treadmill-walking test. Age, weight, height, walk time, and heart rate during the 500-m test were entered into prediction equations previously validated for VO(2)peak estimation from a 1000-m walking test in patients with cardiovascular disease and preserved LVEF.Results: Directly measured and estimated VO(2)peak values were not different (21.6 +/- 4.9 vs 21.7 +/- 4.6 mL/kg/min). The comparison between measured and estimated VO(2)peak values yielded a correlation of R = 0.97 (SEE = 0.7 mL/kg/min, P < 0.0001). The slope and the intercept coincided with the line of identity (Passing and Bablock analysis, P = 0.50). Residuals were normally distributed, and the examination of the Bland-Altman analysis do not show systematic or proportional error.Conclusions: A moderate and self-regulated 500-m treadmill-walking test is a valid tool for VO(2)peak estimation in patients with HFrEF. These findings may have practical implications in the context of transitioning from clinically based programs to fitness facilities or self-guided exercise programs in adults and elderly men with HFrEF

Food-Based dietary guidelines around the World: Eastern Mediterranean and Middle Eastern Countries

In Eastern Mediterranean countries, undernutrition and micronutrient deficiencies coexist with overnutrition-related diseases, such as obesity, heart disease, diabetes and cancer. Many Mediterranean countries have produced Food-Based Dietary Guidelines (FBDGs) to provide the general population with indications for healthy nutrition and lifestyles. This narrative review analyses Eastern Mediterranean countries' FBDGs and discusses their pictorial representations, food groupings and associated messages on healthy eating and behaviours. In 2012, both the WHO and the Arab Center for Nutrition developed specific dietary guidelines for Arab countries. In addition, seven countries, representing 29% of the Eastern Mediterranean Region population, designated their national FBDGs. At the moment several of these guidelines are available only in the English language. In summary, Eastern Mediterranean FBDGs mainly focus on food safety, not all are available in the local Arabic language, and they do not provide specific suggestions for the large number of foreign workers and migrants

Open TURNS: An industrial software for uncertainty quantification in simulation

The needs to assess robust performances for complex systems and to answer tighter regulatory processes (security, safety, environmental control, and health impacts, etc.) have led to the emergence of a new industrial simulation challenge: to take uncertainties into account when dealing with complex numerical simulation frameworks. Therefore, a generic methodology has emerged from the joint effort of several industrial companies and academic institutions. EDF R&D, Airbus Group and Phimeca Engineering started a collaboration at the beginning of 2005, joined by IMACS in 2014, for the development of an Open Source software platform dedicated to uncertainty propagation by probabilistic methods, named OpenTURNS for Open source Treatment of Uncertainty, Risk 'N Statistics. OpenTURNS addresses the specific industrial challenges attached to uncertainties, which are transparency, genericity, modularity and multi-accessibility. This paper focuses on OpenTURNS and presents its main features: openTURNS is an open source software under the LGPL license, that presents itself as a C++ library and a Python TUI, and which works under Linux and Windows environment. All the methodological tools are described in the different sections of this paper: uncertainty quantification, uncertainty propagation, sensitivity analysis and metamodeling. A section also explains the generic wrappers way to link openTURNS to any external code. The paper illustrates as much as possible the methodological tools on an educational example that simulates the height of a river and compares it to the height of a dyke that protects industrial facilities. At last, it gives an overview of the main developments planned for the next few years

Exercise training alone or in combination with high-protein diet in patients with late onset Pompe disease: results of a cross over study

15noBACKGROUND: Late onset Pompe disease (LOPD) is a lysosomal neuromuscular disorder which can progressively impair the patients' exercise tolerance, motor and respiratory functions, and quality of life. The available enzyme replacement therapy (ERT) does not completely counteract disease progression. We investigated the effect of exercise training alone, or associated with a high-protein diet, on the exercise tolerance, muscle and pulmonary functions, and quality of life of LOPD patients on long term ERT. METHODS: The patients were asked to participate to a crossover randomized study comprehending a control period (free diet, no exercise) followed by 2 intervention periods: exercise or exercise + diet, each lasting 26 weeks and separated by 13 weeks washout periods. Exercise training included moderate-intensity aerobic exercise on a cycle ergometer, stretching and balance exercises, strength training. The diet was composed by 25-30% protein, 30-35% carbohydrate and 35-40% fat. Before and after each period patients were assessed for: exercise tolerance test on a cycle-ergometer, serum muscle enzymes, pulmonary function tests and SF36 questionnaire for quality of life. Compliance was evaluated by training and dietary diaries. Patients were contacted weekly by researchers to optimize adherence to treatments. RESULTS: Thirteen LOPD patients, median age 49 ± 11 years, under chronic ERT (median 6.0 ± 4.0 years) were recruited. Peak aerobic power (peak pulmonary O2 uptake) decreased after control, whereas it increased after exercise, and more markedlyafter exercise + diet. Serum levels of lactate dehydrogenase (LDH) significantly decreased after exercise + diet; both creatine kinase (CK) and LDH levels were significantly reduced after exercise + diet compared to exercise. Pulmonary function showed no changes after control and exercise, whereas a significant improvement of forced expiratory volume in 1 sec (FEV1) was observed after exercise + diet. SF36 showed a slight improvement in the "mental component" scale after exercise, and a significant improvement in "general health" and "vitality" after exercise + diet. The compliance to prescriptions was higher than 70% for both diet and exercise. CONCLUSIONS: Exercise tolerance (as evaluated by peak aerobic power) showed a tendency to decrease in LOPD patients on long term ERT. Exercise training, particularly if combined with high-protein diet, could reverse this decrease and result in an improvement, which was accompanied by improved quality of life. The association of the two lifestyle interventions resulted also in a reduction of muscle enzyme levels and improved pulmonary function.openopenSechi A.; Zuccarelli L.; Grassi B.; Frangiamore R.; De Amicis R.; Marzorati M.; Porcelli S.; Tullio A.; Bacco A.; Bertoli S.; Dardis A.; Biasutti L.; Pasanisi M.B.; Devigili G.; Bembi B.Sechi, A.; Zuccarelli, L.; Grassi, B.; Frangiamore, R.; De Amicis, R.; Marzorati, M.; Porcelli, S.; Tullio, A.; Bacco, A.; Bertoli, S.; Dardis, A.; Biasutti, L.; Pasanisi, M. B.; Devigili, G.; Bembi, B

Physical activity and breast cancer survival

Physical activity improves quality of life after a breast cancer diagnosis, and a beneficial effect on survival would be particularly welcome. Four observational studies have now reported decreased total mortality among physically active women with breast cancer; the two largest have also reported decreased breast cancer specific mortality. The estrogen pathway and the insulin pathway are two potential mechanisms by which physical activity could affect breast cancer survival. Randomized trials are ongoing but trials of lifestyle factors are notoriously challenging to perform. Women with breast cancer have little to lose and may possibly gain from moderate exercise

Pediatric cochlear implantation: an update

Deafness in pediatric age can adversely impact language acquisition as well as educational and social-emotional development. Once diagnosed, hearing loss should be rehabilitated early; the goal is to provide the child with maximum access to the acoustic features of speech within a listening range that is safe and comfortable. In presence of severe to profound deafness, benefit from auditory amplification cannot be enough to allow a proper language development. Cochlear implants are partially implantable electronic devices designed to provide profoundly deafened patients with hearing sensitivity within the speech range. Since their introduction more than 30 years ago, cochlear implants have improved their performance to the extent that are now considered to be standard of care in the treatment of children with severe to profound deafness. Over the years patient candidacy has been expanded and the criteria for implantation continue to evolve within the paediatric population. The minimum age for implantation has progressively reduced; it has been recognized that implantation at a very early age (12–18 months) provides children with the best outcomes, taking advantage of sensitive periods of auditory development. Bilateral implantation offers a better sound localization, as well as a superior ability to understand speech in noisy environments than unilateral cochlear implant. Deafened children with special clinical situations, including inner ear malformation, cochlear nerve deficiency, cochlear ossification, and additional disabilities can be successfully treated, even thogh they require an individualized candidacy evaluation and a complex post-implantation rehabilitation. Benefits from cochlear implantation include not only better abilities to hear and to develop speech and language skills, but also improved academic attainment, improved quality of life, and better employment status. Cochlear implants permit deaf people to hear, but they have a long way to go before their performance being comparable to that of the intact human ear; researchers are looking for more sophisticated speech processing strategies as well as a more efficient coupling between the electrodes and the cochlear nerve with the goal of dramatically improving the quality of sound of the next generation of implants

Soft drink and juice consumption and renal cell carcinoma incidence and mortality in the European Prospective Investigation into Cancer and Nutrition

Background: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991–2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. Results: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97–1.09), total soft drinks (HR = 1.01; 95% CI, 0.98–1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94–1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96–1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97–1.16; 1.03, 0.98–1.09; 0.97, 0.89–1.07; and 1.06, 0.99–1.14, respectively). Conclusions: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity

2D protrusion but not motility predicts growth factor–induced cancer cell migration in 3D collagen

Growth factor–induced migration is a critical step in the dissemination and metastasis of solid tumors. Although differences in properties characterizing cell migration on two-dimensional (2D) substrata versus within three-dimensional (3D) matrices have been noted for particular growth factor stimuli, the 2D approach remains in more common use as an efficient surrogate, especially for high-throughput experiments. We therefore were motivated to investigate which migration properties measured in various 2D assays might be reflective of 3D migratory behavioral responses. We used human triple-negative breast cancer lines stimulated by a panel of receptor tyrosine kinase ligands relevant to mammary carcinoma progression. Whereas 2D migration properties did not correlate well with 3D behavior across multiple growth factors, we found that increased membrane protrusion elicited by growth factor stimulation did relate robustly to enhanced 3D migration properties of the MDA-MB-231 and MDA-MB-157 lines. Interestingly, we observed this to be a more reliable relationship than cognate receptor expression or activation levels across these and two additional mammary tumor lines.National Institutes of Health (U.S.) (Grant no. R01- GM081336)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Dept. of Defense. Congressionally Directed Medical Research Programs. Breast Cancer Research Program (Grant no. W81XWH-11-1-0088)United States. Dept. of Defense. Congressionally Directed Medical Research Programs. Breast Cancer Research Program (Grant no. W81XWH-10-1-0040