Quality of life in patients with chordomas/chondrosarcomas during treatment with proton beam therapy

Introduction: Health-related quality of life (HQL) parameters have never been tested in patients having chondromas/chondrosarcomas who are being treated with protons. The aim of this study was to document changes in HQL of chordoma/chondrosarcoma patients treated with proton beam radiotherapy. Treatments commenced in September 2011 at CNAO, and HQL studies were initiated in January 2012 for all patients undergoing treatment. Methods: The validated Italian translation of the EORTC QLQ-C30 version 3.0 was used for HQL evaluation. The HQL assessments were made prior to starting radiation and at completion of treatment. Scoring was as per the EORTC manual. As per standard norms, a difference of >10 points in the mean scores was taken to be clinically meaningful. Results: Between January and September 2012, 17 patients diagnosed with chordoma or chondrosarcoma, with a mean \ub1 SD age of 49.5 \ub1 16.4 years, had completed treatment. The involved sites were skull base (n = 12) and sacral/paraspinal (n = 5). The prescribed dose was 70-74 GyE at 2 GyE per fraction, 5 days/week. When comparing pre- and post-treatment scores, neither a clinically meaningful nor a statistically significant change was documented. Conclusions: During treatment, HQL is not adversely affected by protons, allowing normal life despite the long course of treatment. This is an ongoing study and more long-term assessment will help evaluate the actual impact of proton therapy on HQL for these slow-responding tumours

The compound Poisson limit ruling periodic extreme behaviour of non-uniformly hyperbolic dynamics

We prove that the distributional limit of the normalised number of returns to small neighbourhoods of periodic points of non-uniformly hyperbolic dynamical systems is compound Poisson. The returns to small balls around a fixed point in the phase space correspond to the occurrence of rare events, or exceedances of high thresholds, so that there is a connection between the laws of Return Times Statistics and Extreme Value Laws. The fact that the fixed point in the phase space is a repelling periodic point implies that there is a tendency for the exceedances to appear in clusters whose average sizes is given by the Extremal Index, which depends on the expansion of the system at the periodic point. We recall that for generic points, the exceedances, in the limit, are singular and occur at Poisson times. However, around periodic points, the picture is different: the respective point processes of exceedances converge to a compound Poisson process, so instead of single exceedances, we have entire clusters of exceedances occurring at Poisson times with a geometric distribution ruling its multiplicity. The systems to which our results apply include: general piecewise expanding maps of the interval (Rychlik maps), maps with indifferent fixed points (Manneville-Pomeau maps) and Benedicks-Carleson quadratic maps.Comment: To appear in Communications in Mathematical Physic

Initial clinical experience with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO)

We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35-37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21-74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70-74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy

Numerical convergence of the block-maxima approach to the Generalized Extreme Value distribution

In this paper we perform an analytical and numerical study of Extreme Value distributions in discrete dynamical systems. In this setting, recent works have shown how to get a statistics of extremes in agreement with the classical Extreme Value Theory. We pursue these investigations by giving analytical expressions of Extreme Value distribution parameters for maps that have an absolutely continuous invariant measure. We compare these analytical results with numerical experiments in which we study the convergence to limiting distributions using the so called block-maxima approach, pointing out in which cases we obtain robust estimation of parameters. In regular maps for which mixing properties do not hold, we show that the fitting procedure to the classical Extreme Value Distribution fails, as expected. However, we obtain an empirical distribution that can be explained starting from a different observable function for which Nicolis et al. [2006] have found analytical results.Comment: 34 pages, 7 figures; Journal of Statistical Physics 201

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Retinol Blood Levels In High School Students Of São Paulo, Brazil [retinol Sérico De Adolescentes De Uma Escola Da Cidade De São Paulo]

Objective: The purpose of the study was to examine plasma retinol levels in 218 adolescents of both sexes, ages 10 to 19 years old. All the subjects attended a private high school in the city of São Paulo. Methods: In order to evaluate the students' nutritional condition, the researchers performed anthropometrical measurements - weight and height - in addition to investigating the subjects' diet history. The retinol level was measured through the spectrophotometer technique, considering as inadequate values of concentration under <1.05μmol/L (30μg/dL). Results: The results indicate that the average intake, according to the age range, was higher than recommended, even though presenting high deviation patterns for both genders. The percentage of teenagers with plasma concentrations of vitamin A under the adequate level was 30% for both genders, and neither the analysis of the correlation between Body Mass Index and plasma concentrations of retinol, nor the analysis of the correlation between the density of vitamin A intake and plasma concentration of retinol, were significant. Conclusion: The research findings point out to the need for further investigation of vitamin A concentrations during adolescence, in order to check more accurately whether the low plasma concentration of this nutrient should be considered a risk factor, or the result of the accelerated absorption which takes place in adolescence to fulfill the metabolic requirements characteristic of this period of human growth.173291299West Jr., K.P., Dietary vitamin A deficiency: Effects on growth, infection, and mortality (1991) Food Nutr Bull, 13, pp. 119-131Evaion-Brior, D., Porquet, D., Therrond, P., Paulsen, A.F., Grenede, M.O., François, L., Vitamin A and nocturnal growth hormone secretion in short children (1994) Lancet, 343, pp. 87-88Herberth, B., Spyckerelle, Y., Deschamps, J.P., Determinants of plasma retinol b-carotenoid and a-tocopherol during adolescence (1991) Am J Clin Nutr, 54, pp. 884-889Brabin, L., Brabin, B., The cost successful adolescent growth and development in girls in relation to iron and vitamin A status (1992) Am J Clin Nutr, 55 (5), pp. 955-958(2000) Dietary Assessment, , Washington, DC: The Nacional Academy PressGama, C.M., (1999) Consumo Alimentar e Estado Nutricional de Adolescentes Matriculados na Rede de Ensino Particular e Pública do Bairro de Vila Mariana da Cidade de São Paulo, São Paulo, , [tese]. São Paulo: Pós-Graduação em Nutrição, Universidade Federal de São Paulo, Escola Paulista de MedicinaBatista Filho, M., Alimentação, nutrição e saúde (1999) Epidemiologia e Saúde. 5.Ed., pp. 353-374. , Rouquayrol MZ, Almeida Filho N. São Paulo: MEDSIRoncada, M.J., Wilson, D., Mazzilli, R.N., Gandra, Y.R., (1981) Hipovitaminose A em Comunidades do Estado de São Paulo, Brasil, 15, pp. 338-349. , Rev Saude PublicaWilson, D., Silva Nery, M.E., Hypovitaminosis A in Rio Grande do Sul, Brazil. Preliminary study (1983) Int J Vitam Res Suppl, 24, pp. 35-44Flores, H., Araújo, C.R., Liver levels of retinol in unselect necropsy specimens: A prevalence survey of vitamin A deficiency in Recife, Brazil (1984) Am J Clin Nutr, 40 (1), pp. 146-152Thompson, F.E., Byers, T., Dietary assessment resource manual (1994) J Nutr, 124 (SUPPL. 11), pp. 22455-23015Anção, M.S., Cuppari, L., Tudisco, E.S., Draibe, A.S., Sigulen, D.M., (1993) Sistema de Apoio à Decisão em Nutrição, Versão 2.5, , Centra de Informática em Saúde da Universidade Federal de São Paulo, Escola Paulista de Medicina. São Paulo(1996) Estudo Nacional de Despesa Familiar (ENDEF): Tabela de Composição de Alimentas. 4.Ed., , Secretaria de Planejamento da República. Rio de Janeiro: DEDIT/CDDIPinheiro, A.B., Lacerda, E.M.A., Benzercry, E., Gomes, M.C.S., Costa, V.M., (1996) Tabela para Avaliação de Consumo Alimentar em Medidas Caseiras. 3.Ed., , Rio de Janeiro: Produção IndependenteHansen, R.G., Wyse, B.W., Expression of nutrient allowances per 1000 kilocalories (1980) J Am Diet Assoc, 76 (3), pp. 233-227Must, A., Dallal, G.E., Dietz, W.H., Reference data for obesity: 85th and 95th percentiles of body mass index (wt/ht2) - A correction (1991) Am J Clin Nutr, 54, p. 773(1995) Physical Status: The Use and Interpretation of Anthropometry, , Geneva: World Health Organization. Technical Report Series n.854Bessey, O., Lowry, O.H., Brock, M.J., Lopez, J.A., The determination of vitamin A and carotene in small quantities of blood serum (1946) J Biol Chem, 11, pp. 177-188Araujo, C.R.C., Flores, H., Improved spectrophotometric vitamin A assay (1978) Letters Clin Chem, 24 (2), p. 386Flores, H., Importance of the early diagnosis of vitamin A deficiency at the epidemiological level (1983) Int J Vitam Res, 24, pp. 23-24Siegel, S., Castellan Jr., N.J., (1988) Nonparametrics Statistics, , New York: McGraw-HillDietary reference intakes (2003) Application in Dietary Planning, , Washington, DC: The National Academic Press: 2003. 237pUnderwood, B.A., Arthur, A., The contribuition of vitamin A to public health (1996) FASEB J, 10, pp. 1040-1048Sommer, A., (1995) Vitamin A Deficiency and Its Consequences: A Fiel Guide to Detection and Control - Epidemiology, pp. 1-73. , Geneva: World Health OrganizationSouza Queiroz, S., Sato, K., Torres, M.A.A., Detection of the prevalence of hipovitaminose A in children under 2 years of age enrolled in Basic Health care units cities of State of São Paulo (1998) 16th Proceedings of the Congress of Nutrition, p. 292. , 1998, Montréal. Montréal. (PT 659)Neuhouser, M.L., Rock, C.L., Eldrige, A.L., Kristal, A.R., Patterson, R.E., Cooper, D.A., Serum concentration of retinol, a-tocopherol and the carotenoids are influenced by diet, race and obesity in a sample of healthy adolescents (2001) J Nutr, 131, pp. 2184-2191Lewis, C.J., Mc Dowell, M.A., Sempos, C.T., Lewis, K.C., Yetley, E.A., Relationship between age and serum vitamin A in children age 4-11 (1990) Am J Clin Nutr, 52 (2), pp. 353-360Olson, J.A., Atwater Lecture. The irresistible fascination of carotenoids and vitamin A (1993) Am J Clin Nutr, 57 (6), pp. 833-839Lee, R.D., Nieman, D.C., (1995) Nutritional Assessment - Anthropometric, Biochemical, Clinical, Dietary, , St Louis: MOSB

The Influence Of Sardine Consumption On The Omega-3 Fatty Acid Content Of Mature Human Milk

Objectives: The purpose of this study was to investigate what effect the ingestion of sardines, rich in omega-3 series polyunsaturated fatty acids, has on the composition of breastmilk. Methods: This was a prospective study of 31 nursing mothers under observation at the Hospital Guilherme Álvaro. Each was given 2 kg of fresh sardines twice with a 15-day interval. Milk was sampled and a 24-hour dietary recall questionnaire was applied on days 0, 15 and 30. Milk was assayed for fatty acid content by gas chromatography. Statistical analysis of the results was performed using nonparametric tests with significance set at p &lt; 0.05. Results: The results demonstrate that the nutritional intake of the nursing mothers was adequate at all three sample points. With regard to the omega-3 series fatty acid content of the breastmilk, it was observed that regular consumption and shorter intervals between ingestion and milk collection resulted in higher concentrations of docosapentaenoic acid and docosahexaenoic acid at 15 and 30 days into the study. Fatty acids from the omega-3 and omega-6 series exhibited a significant correlation, r2 was 0.58 and 0.59 at 15 and 30 days, respectively. Conclusion: These results suggest that incorporating fish into the diets of nursing mother during lactation, in the form of 100 g of sardines two or three times a week, contributes to an increase in omega-3 series fatty acids. Copyright © 2006 by Sociedade Brasileira de Pediatria.8216369Martinez, M., Tissue levels of polyunsaturated fatty acids during early human development (1992) J Pediatr, 120 (4 PART 2), pp. S129-38Xiang, M., Alfvén, G., Blennow, M., Trygg, M., Zetterstrom, R., Long-chain polyunsaturated fatty acids in human milk and brain growth during early infancy (1999) Acta Paediatr, 89, pp. 142-147Montgomery, C., Speake, K.B., Cameron, A., Sattar, N., Weaver, L.T., Maternal docosahexaenoic acid supplementation and fetal accretion (2003) Br J Nutr, 90, pp. 135-145Koletzko, B., Rodríguez-Palmero, A., Demmelmair, H., Fildler, N., Jensen, R., Sauerwald, T., Physiological aspects of human milk lipids (2001) Early Hum Dev, 65 (SUPPL.), pp. S3-18Presa-Owens, S., López-Sabater, M.C., Rivero-Urgell, M., Fatty acid composition of human milk in Spain (1996) J Pediatr Gastroenterol Nutr, 22, pp. 180-185Jørgensen, M.H., Hernell, O., Lund, P., Hølmer, G., Michaelsen, K.F., Visual acuity and erythrocyte docosahexaenoic acid status in breast-fed and formula-fed term infants during the first four months of life (1996) Lipids, 31, pp. 99-105Rocquelin, G., Tapsoba, S., Dop, M.C., Mbemba, F., Traissac, P., Martin-Prével, Y., Lipid content and essential fatty acid (EFA) composition of mature Congolese breast milk are influenced by mothers' nutritional status: Impact on infants' EFA supply (1998) Eur J Clin Nutr, 52, pp. 162-171Lauritzen, L., Jorgensen, M.L., Hansen, H.S., Michaelsen, K.F., Fluctuations in human milk long-chain PUFA levels in relation to dietary fish intake (2002) Lipids, 37, pp. 237-244Hartman, L., Lago, R.C., Rapid preparation of fatty acid methyl esters from lipids (1973) Lab Proc, 22, pp. 475-477Jensen, R.G., Bitman, J., Carlson, S.E., Couch, S.C., Hamosh, M., Neuwburg, D.S., Human milk lipids (1995) The Handbook of Milk Composition, pp. 495-537. , Jensen RG. San Diego: Academic PressHenderson, R.A., Jensen, R.G., Lammi-Keefe, C.J., Ferris, A.M., Dardick, K.R., Effect of fish oil on the fatty acid composition of human milk and maternal and infant erythrocytes (1992) Lipids, 27, pp. 863-869Obesity: Preventing and managing the global epidemic (1997) Report of a WHO Consultation on Obesity, , Geneva: WHOThompson, F.E., Byers, T., Dietary assessment resource manual (1994) J Nutr, 124 (11 SUPPL.), pp. S2245-317Anção, M.S., Cuppari, L., Tudisco, E.S., Draibe, A.S., Sigulen, D., (1995) Sistema de Apoio à Decisão Em Nutrição [Programa de Computador] Versão 2.5, , São Paulo: Centro de Informática em Saúde-Universidade Federal de São Paulo (UNIFESP/EPM)Marmet, C., Extração manual do leite do seio: Técnica de Marmet (1981) Aleitamento Materno: Separata para Profissionais. Folheto Informativo 27, , Los Angeles: La Leche League InternationalFolch, J., Lees, M., Sloan-Stanley, G.H., A simple method for the isolation and purification of total lipids from animal tissue (1957) J Biol Chem, 226, pp. 497-509James, A.T., Martin, A.J., Gas liquid chromatography: The separation and identification of the methyl esters of saturated and unsaturated acids from formic acid to n-octadecanoic acid (1956) Biochem J, 63, pp. 144-152Siegel, S., (1975) Estatística No Paramétrica, , Cidade do México: TrillasSauerwald, T.U., Demmelmair, H., Koletzko, B., Polyunsaturated fatty acid supply with human milk (2001) Lipids, 36, pp. 991-996Philippi, S.T., Latterza, A.R., Cruz, A.T., Ribeiro, L.C., Pirâmide alimentar adaptada: Guia para escolha dos alimentos (1999) Rev Nutr, 12, pp. 65-80Comment on the content and composition of lipids in infant formulas (1991) Acta Paediatr Scand, 80, pp. 887-896. , Committee ReportCoelho, M.R., Nóbrega, F.J., Estudo das gorduras totais, valor calórico total e proteínas totais no colostro de puérperas, segundo o nível sócio-econômico, o estado nutricional e a paridade (1989) J Pediatr (Rio J), 65, pp. 7-11Brasil, A.L., Vítolo, M.R., Ancona Lopez, F., Nóbrega, F.J., Fat and protein composition of mature milk in adolescents (1991) J Adolesc Health Care, 12, pp. 365-371Silva, M.P., Nóbrega, F.J., Ancona Lopez, F., Vítolo, M.R., Queiroz, S.S., Lipid composition (Total fats, caloric value and fatty acids) in the colostrum of adult nursing mothers of large for gestational age infants (1996) Human Milk Composition, pp. 171-180. , Nóbrega FJ. São Paulo: RevinterBell, S.J., Bradley, D., Forse, R.A., Bistrian, B.R., The new dietary fats in health and disease (1997) J Am Diet Assoc, 97, pp. 280-286Insull, W., Hirsch, J., James, T., Ahrens, E.H., The fatty acids of human milk. II. Alterations produced by manipulation of caloric balance and exchange of dietary fats (1959) J Clin Invest, 38, pp. 443-450Marckmann, P., Lassen, A., Haraldsdóttir, J., Sandström, B., Biomarkers of habitual fish intake in adipose tissue (1995) Am J Clin Nutr, 62, pp. 956-959Vidgen, H.M., Agren, J.J., Schwab, U., Rissanen, T., Hanninen, O., Uusitupa, M.I.J., Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexanoic acid - Rich oil among healthy young men (1997) Lipids, 32, pp. 697-705Huang, Y.S., Wainwright, P.E., Redden, P.R., Mills, D.E., Bulman-Fleming, B., Horrobin, D.F., Effect of maternal dietary fats with variable n-3/n-6 ratios on tissue fatty acid composition in suckling mice (1992) Lipids, 27, pp. 104-110Harris, W.S., Connor, W.E., Lindsey, S., Will dietary n-3 fatty acids change the composition of human milk? (1984) Am J Clin Nutr, 40, pp. 780-78

Radiation therapy for retroperitoneal sarcoma

Purpose Retroperitoneal sarcomas (RPS) are rare tumours with an annual reported incidence of 2.7 per million persons. In spite of improvements in both diagnostic imaging and therapeutic strategies, patients afflicted by RPS still have poor prognoses. There are currently many different therapeutic strategies for these rare tumours and combining several different multi-modality strategies have not proved to have superior long-term clinical results. This review analyses the available published data and discusses multi-modality management of this rare entity. In particular, the role of radiation therapy, treatment-related side effects and the use of modern radiation treatment techniques will be discussed. Materials and methods A comprehensive literature search was conducted using PubMed in January 2011. Relevant international articles published from January 1980 to January 2011 were assessed. The keywords for search purposes were: retroperitoneum, sarcoma, radiotherapy, and radiation therapy. The search was limited to articles published in English. All articles were read in full by the authors and selected for inclusion based on relevance to this article. Conclusions The addition of radiation therapy (RT) to wide surgical excision for RPS has improved local control rates when compared with surgery alone. Preoperative RT is preferred over postoperative RT. New types and delivery techniques in radiation therapy could further improve patient outcomes. Emerging therapies that employ charged particles (such as protons and carbon ions) are expected to be superior in sparing of normal tissues and efficacy over conventional photon therapy radiation, due to their physical and radiobiological properties