Póvoa de Santa Iria, Portugal
Póvoa de Santa Iria, Portugal

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Boleo-Tome C.,University of Lisbon | Chaves M.,University of Lisbon | Monteiro-Grillo I.,Hospital Universitario Of Santa Maria | Camilo M.,University of Lisbon | Ravasco P.,University of Lisbon
Oncologist | Year: 2011

Rationale. Nutritional risk screening should be routine in order to select patients in need of nutrition care; this conduct change has to rely on education. In this project, radiotherapy department health professionals were trained on how to use the Malnutrition Universal Screening Tool (MUST), to foster its integration into cancer outpatient management; we also aimed to identify those more adherent to screening. Methods. Research dieticians (the standard) conducted interactive sessions with all physicians, nurses, and radiotherapy (RT) technicians, who were closely supervised to facilitate routine MUST integration. There were two phases: after the first session, phase 1 assessed 200 patients over 4 months; after the second session, phase 2 screened 450 patients, always before RT. Validity was evaluated comparing results from the standard against all other health professionals, adjusted for number. Results. RT technicians were most adherent to the MUST: 80% of patients in phase 1, increasing to 85% in phase 2. Nurses doubled their input, from 19% to 36%. Physicians had poor MUST integration, yet they progressively incorporated percentage weight loss into patient records, increasing from 57% in phase 1 to 84% in phase 2, independently of diagnosis and stage. The highest concordance (_ coefficient) with dieticians was found with RT technicians' use of the MUST (p <002) and percentage weight loss determination by physicians (p <001). Conclusions. We show that systematic screening in cancer is feasible by all professionals involved, once a proximity teaching project is put into practice. RT technicians, who daily treat patients, were highly adherent to integrate the MUST and might be in charge of selecting at-risk patients. Physicians are unlikely to use the MUST, but acknowledged nutrition value and changed their routine by integrating recent percentage weight loss into their approach to patients. Our structured methodology may be used as a model for the development of teaching adapted to different departments with other realities. © AlphaMed Press.


Boleo-Tome C.,University of Lisbon | Monteiro-Grillo I.,University of Lisbon | Monteiro-Grillo I.,Hospital Universitario Of Santa Maria | Camilo M.,University of Lisbon | Ravasco P.,University of Lisbon
British Journal of Nutrition | Year: 2012

In the present study, we aimed to validate the Malnutrition Universal Screening Tool (MUST) for routine nutritional screening in the radiation oncology setting, thus enabling timely and adequate referrals of patients at risk for individualised or advanced intervention. Towards this objective, we conducted a prospective cross-sectional study in 450 non-selected cancer patients (18-95 years) referred for radiotherapy. The following were the nutritional parameters: BMI (categorised by WHO's age/sex criteria), weight loss >5% in the previous 3-6 months, Patient-Generated Subjective Global Assessment (PG-SGA-validated/specific for oncology) and nutritional risk by MUST. Sensitivity, specificity, predictive values and concordance were calculated to validate MUST v. PG-SGA and compare single parameters v. PG-SGA/MUST. BMI v. PG-SGA showed a negligible capacity to detect undernutrition: 0•27 sensitivity, 0•23 specificity, 0•35 positive predictive value and 0•31 negative predictive value. Conversely, percentage weight loss v. PG-SGA was highly effective: 0•76 sensitivity, 0•85 specificity, 0•79 positive predictive value and 0•85 negative predictive value. MUST v. PG-SGA successfully detected patients at risk: 0•80 sensitivity, 0•89 specificity, 0•87 positive predictive value and 1•0 negative predictive value; percentage weight loss v. MUST proved able to identify patients likely to be at risk: 0•85 sensitivity, 0•91 specificity, 0•90 positive predictive value and 1•0 negative predictive value. This is the first study in the radiation oncology setting to validate MUST: a simple and quick method applicable by any health professional, with a high validity for early screening, ideally to antedate a comprehensive nutritional assessment and guide for intervention. In this study, percentage weight loss in the previous 3-6 months does seem valid to predict nutritional risk, and may be the minimum in a busy routine. © 2011 The Authors.


Mota C.,University of Lisbon | Mota C.,Hospital Universitario Of Santa Maria | Nunes-Silva V.,University of Lisbon | Pires A.R.,University of Lisbon | And 5 more authors.
Journal of Immunology | Year: 2014

FOXP3-expressing regulatory T cells (Treg) are essential for the prevention of autoimmunity and were shown to be reduced and/or dysfunctional in several autoimmune diseases. Although Treg-based adoptive transfer represents a promising therapy, the large cell number required to achieve clinical efficacy constitutes an important limitation. Therefore, novel strategies to generate bona fide in vitro-induced Treg (iTreg) are critical. In this study, we report that human memory CD4 T cells can be efficiently converted into iTreg, and that Delta-like 1 (DL1)-mediated Notch signaling significantly enhances this process. The iTreg generated in the presence of DL1 featured higher levels of Treg function-associated molecules and were efficient suppressors. Importantly, these iTreg displayed a stable phenotype in long-term cultures, even in the presence of proinflammatory cytokines. Additionally, DL1 potentiated FOXP3 acquisition by memory CD4 cells through the modulation of the TGF-β signaling pathway and of Foxp3 transcription. Our data demonstrate that iTreg can be efficiently induced from memory CD4 cells, a subset enriched in relevant specificities for targeting in autoimmune diseases, and that DL1 enhances this process. DL1 also enhanced the proliferation and Treg function-associated marker expression of ex vivo-stimulated human circulating FOXP3+ cells. Manipulation of the Notch signaling pathway constitutes a promising approach to boost the in vitro generation of iTreg and ex vivo Treg expansion, thus facilitating the establishment of effective Treg-based adoptive therapy in autoimmune diseases. Copyright © 2014 by The American Association of Immunologists, Inc.


Ravasco P.,Institute Medicina Molecular | Monteiro-Grillo I.,Institute Medicina Molecular | Monteiro-Grillo I.,Hospital Universitario Of Santa Maria | Camilo M.,Institute Medicina Molecular
American Journal of Clinical Nutrition | Year: 2012

Background: In our published randomized trial in colorectal cancer, group 1 (n = 37) received individualized nutritional counseling and education about regular foods, group 2 (n = 37) received dietary supplements and consumed their usual diet of regular foods, and group 3 (n = 37) consumed their usual diet of regular foods. Neither group 2 nor group 3 received individualized counseling. Early nutritional counseling during radiotherapy was highly effective at reducing acute radiotherapy toxicity and improving nutritional intake/status and quality of life (QoL). Efficacy persisted for 3 mo after the intervention. Objective: The objective was to perform long-term follow-up in survivors of that clinical trial to specifically evaluate survival, late toxicity, QoL, and nutritional variables. Design: Medical data were collected from patients' records, and pre-scheduled interviews were conducted by dietitians for individualized evaluations. Analyses and comparisons between groups (adjusted for stage) were performed after a median follow-up of 6.5 (range: 4.9-8.1) y. Results: Patients complied with the Radiotherapy Department's follow-up protocol. Nutritional deterioration was higher (P < 0.001) in group 3 (n = 26) and group 2 (n = 29) than in group 1 (n = 34). Adequate nutritional status was maintained in 91% of group 1 patients but not in any of the group 3 patients (P < 0.002). Intakes in group 1 were similar to reference values, and the patients adhered to the prescribed recommendations. Intakes in groups 2 and 3 were lower than recommended intakes: group 3 ≃ group 2 < group 1 (P = 0.001). Median survival in group 3 was 4.9 y (30% died), in group 2 was 6.5 y (22% died), and in group 1 was 7.3 y (only 8% died): group 3 > group 2 > group 1 (P < 0.01). Late radiotherapy toxicity was higher in group 3 (n = 17; 65%) and group 2 (n = 17; 59%) than in group 1 (n = 3; 9%): group 3 ≃ group 2 > group 1 (P < 0.001). QoL was worse in groups 3 and 2 than in group 1: group 3 ≃ group 2 < group 1 (P < 0.002). Worse radiotherapy toxicity, QoL, and mortality were associated with deteriorated nutritional status and intake (P < 0.001). Likewise, depleted intake, nutritional status, and QoL predicted shorter survival and late toxicity (HR: 8.25; 95% CI: 2.74, 1.47; P < 0.001). Conclusions: This study conveys novel information about the effectiveness of nutrition at improving long-term prognosis in colorectal cancer. Overall, the data indicate that early individualized nutritional counseling and education during radiotherapy is valuable for patients. © 2012 American Society for Nutrition.


Machado M.V.,Hospital Universitario Of Santa Maria | Cortez-Pinto H.,Hospital Universitario Of Santa Maria
World Journal of Gastroenterology | Year: 2014

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. © 2014 Baishideng Publishing Group Inc. All rights reserved.


Ravasco P.,Hospital Universitario Of Santa Maria
Nutrition | Year: 2015

Intensive individualized nutritional counseling requires nutrition professionals with specific experience in oncology. If the patient is unable to achieve his or her nutritional requirements via regular foods, nutritional supplements may be prescribed, the composition of which is based on detection of dietary deficits as well as a detailed intake questionnaire. Any nutritional intervention must be based on the need for an adequate intake and also must take into consideration other relevant factors such as digestive and absorptive capacity, the need for alleviation or arrest of symptoms, and any psychological issues. © 2015 Elsevier Inc.


MacHado M.V.,Hospital Universitario Of Santa Maria | MacHado M.V.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Hospital Universitario Of Santa Maria | Cortez-Pinto H.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Servio
Journal of Hepatology | Year: 2011

It has been recognized that some lean individuals unexpectedly present with non-alcoholic steatohepatitis (NASH) [1] and in contrast, morbidly obese individuals present NASH in only about 14-37% of cases [2]. Although this situation is seemingly paradoxical, the discrepancy has been mostly attributed to the pattern of obesity being predominantly visceral/truncal, or peripheral/subcutaneous. Obesity, and particularly visceral fat (VF), is considered a key player in the development of the metabolic syndrome and its complications, namely cardiovascular risk and non-alcoholic fatty liver disease (NAFLD). Indeed, waist circumference, considered an indirect measurement of VF, is one criterion in the metabolic syndrome definition. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Santos-Ribeiro S.,Vrije Universiteit Brussel | Santos-Ribeiro S.,Hospital Universitario Of Santa Maria | Polyzos N.P.,Vrije Universiteit Brussel | Haentjens P.,Vrije Universiteit Brussel | And 4 more authors.
Human Reproduction | Year: 2014

Studyquestion: Are low serum progesterone levels on the day of human chorionic gonadotrophin (hCG) administration detrimental for live birth delivery rates during in vitro fertilization (IVF)? Summary answer: Progesterone levels ≤0.5 ng/ml on the day of hCG administration hinder live birth rates. What is known already: Fundamental research has shown that the presence of late follicular phase progesterone is essential for follicular development, ovulation and endometrial receptivity. However, previous studies in patients undergoing ovarian stimulation have only assessed if progesterone levels in the higher range are detrimental for pregnancy or not. That said, information on the effect of the full range of late follicular progesterone on IVF outcomes is still lacking. Study design, size, duration: This was a retrospective, single-centre cohort study with 2723 cycles performed in patients aged between 19 and 36 and undergoing controlled ovarian stimulation between January 2006 and March 2012 for their first or second attempt of IVF followed by a fresh embryo transfer (ET). Participants/materials, setting, methods: All patients underwent ovarian stimulation using a gonadotrophin-releasing hormone (GnRH) antagonist for pituitary down-regulation. Final oocyte maturation was triggered with hCG 36 h before oocyte retrieval. On the day of hCG administration, serum progesterone evaluation was performed. Live birth delivery rates were compared amongst various ordinal and regular progesterone intervals (≤0.50, 0.50-0.75, 0.75-1.00, 1.00-1.25, 1.25-1.50, >1.50 ng/ml) using logistic regression. Main results and the role of chance: The average age of our sample was 30.5 years. Almost 82% of all embryo transfers were of a single embryo and 51.8%were performed with a Day 5 embryo. The average value (±standard deviation) of progesterone on the day of hCG administration was 1.02 ± 0.50 ng/ml and the live birth rate was 23.4%. The live birth rates (according to the above-described ordinal serum progesterone intervals) were 17.1, 25.1, 26.7, 25.5, 21.9 and 16.6%, respectively. The live birth rates were significantly lower in patients with both low (≤0.5 ng/ml) and high (>1.5 ng/ml) late follicular progesterone levels (P < 0.05). Limitations, reasons for caution: The main limitation of our study was its retrospective nature. Furthermore, our study was restricted to patients under GnRH antagonist pituitary suppression and requires confirmation in a GnRH agonist setting. Wider implications of the findings: This study comprehensively assessed the relationship between live birth delivery rates and progesterone levels on the day of hCG administration during ovarian stimulation for IVF. Clinically relevant lower (≤0.5 ng/ml) and higher (>1.5 ng/ml) progesterone level limits were determined. © The Author 2014.


MacHado M.V.,Hospital Universitario Of Santa Maria | MacHado M.V.,Institute Medicina Molecular IMM | Cortez-Pinto H.,Hospital Universitario Of Santa Maria | Cortez-Pinto H.,Institute Medicina Molecular IMM
Expert Review of Gastroenterology and Hepatology | Year: 2011

Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the Western world. Progression to more aggressive forms of liver injury, such as nonalcoholic steatohepatitis (NASH) and cirrhosis, occurs in less than a third of affected subjects. Human data and both in vivo and in vitro models demonstrate that cell death, particularly apoptosis, is increased in NAFLD and NASH patients, suggesting that it is crucial in disease progression. Indeed, fatty acids-more specifically, saturated fatty acids-strongly induce hepatocyte apoptosis. In addition, hepatic steatosis renders hepatocytes more susceptible to apoptotic injury. Ballooned hepatocytes and Mallory-Denk bodies are important hallmarks of NASH and correlate with disease progression. There are complex correlations between ballooning, Mallory-Denk bodies and apoptosis through keratin metabolism and depletion, as well as through the endoplasmic reticulum stress response. Whether apoptosis may promote hepatocellular ballooning, or vice versa, will be discussed in this article. © 2011 Expert Reviews Ltd.


Oliveira D.C.,Federal University of Santa Maria | Markus Lopes P.G.,Federal University of Santa Maria | Spader T.B.,Federal University of Santa Maria | Mahl C.D.,Federal University of Santa Maria | And 4 more authors.
Journal of Clinical Microbiology | Year: 2011

We studied 40 strains of the species complex formerly classified as the single species Sporothrix schenckii to identify new species within this complex and evaluate their antifungal susceptibility profiles. Based on phenotypic tests (ability to grow at 37°C, colony diameters, and pigmentation of the colonies, as well as assimilation of sucrose and raffinose) and molecular assays (amplification of a fragment of the calmodulin gene), here we report the identification of S. albicans, S. brasiliensis, S. luriei, and S. schenckii; two isolates of these species were detected as itraconazole-resistant strains. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

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