IL-2 AND IFN-g, BUT NOT IL-4 SECRETION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) ARE RELATED TO CD4+ T CELLS AND CLINICAL STATUS IN BRAZILIAN HIV-1-INFECTED SUBJECTS

It has been reported that production of IL-2 and IFN-g, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC) decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV- infected patients and normal subjects, were detected. The patients with CD4+ T cell counts <200 showed a significant decrease of IL-2 and IFN-g production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or >500 cells/mm3) also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-g release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells >500 cells/mm3 showed increased levels of IL-2 and IFN-g, than individuals with CD4+ T cells <500 cells/mm3. In conclusion, we observed a decline of IL-2 and IFN-g production at advanced HIV disease. IL-4 production was not affected during HIV infection. Taken together, these findings suggest that the cytokine profile might be influenced by the HIV infection rather than the cause of disease progression.

Jejunal perforation caused by abdominal angiostrongyliasis

The authors describe a case of abdominal angiostrongyliasis in an adult patient presenting acute abdominal pain caused by jejunal perforation. The case was unusual, as this affliction habitually involves the terminal ileum, appendix, cecum or ascending colon. The disease is caused by the nematode Angiostrongylus costaricensis, whose definitive hosts are forest rodents while snails and slugs are its intermediate hosts. Infection in humans is accidental and occurs via the ingestion of snail or slug mucoid secretions found on vegetables, or by direct contact with the mucus. Abdominal angiostrongyliasis is clinically characterized by prolonged fever, anorexia, abdominal pain in the right-lower quadrant, and peripheral blood eosinophilia. Although usually of a benign nature, its course may evolve to more complicated forms such as intestinal obstruction or perforation likely to require a surgical approach. Currently, no efficient medication for the treatment of abdominal angiostrongyliasis is known to be available. In this study, the authors provide a review on the subject, considering its etiopathogeny, clinical picture, diagnosis and treatment.

Desigualdades socioeconómicas na doença cardiovascular em Portugal : estudo baseado no 4º Inquérito Nacional de Saúde

RESUMO - Em Portugal, as doenças cardiovasculares (DCV), incluindo o acidente vascular cerebral (AVC) e a doença cardíaca isquémica (DCI), são das principais causas de morbi-mortalidade e invalidez. Sabe-se que o nível socioeconómico (NSE) influencia o estado de saúde, todavia são escassas as evidências sobre as desigualdades socioeconómicas na DCV em Portugal. O objectivo deste estudo foi analisar a distribuição da DCV de acordo com o NSE na população portuguesa. Foi realizado um estudo transversal exploratório-descritivo usando a base de dados do 4º Inquérito Nacional de Saúde, 2005/06. As desigualdades socioeconómicas nas DCV, AVC e DCI, factores de risco [sedentarismo, hipertensão arterial (HTA), diabetes mellitus (DM), tabagismo, obesidade e sofrimento psicológico (Mental Health Inventory ≤ 52)] e número de consultas médicas, foram analisadas através dos odds ratio por NSE (rendimento familiar equivalente, escala modificada da OCDE) com intervalo de confiança de 95% e dos índices e curvas de concentração. Dos 21 807 indivíduos, 53,34% são do sexo feminino, a idade média é de 54±11 e entre 35 e 74 anos. A DCV, a DCI, o AVC, a HTA, a DM e a obesidade estão associados com NSE mais baixos, o tabagismo está associado aos NSE mais elevados, enquanto o sedentarismo, o número de consultas médicas e o sofrimento psicológico não apresentam associação significativa com o NSE. Os resultados revelam a associação entre os estilos de vida, morbilidade e NSE e demonstram que são necessárias políticas de saúde mais abrangentes, de acordo com as características individuais, culturais e socioeconómicas e dirigidas à promoção da saúde e prevenção da doença. -------------------------------------------- ABSTRACT - Cardiovascular diseases (CVD), including stroke and ischemic heart disease (IHD), are the leading causes of morbidity, mortality and disability in Portugal. It is known that socioeconomic status (SES) influences health status; however there is little evidence about socioeconomic inequalities in CVD in Portugal. The aim of this study was to analyze the distribution of CVD according to SES in the Portuguese population. We conducted a cross-sectional descriptive exploratory study using the database of the 4th National Survey of Health, 2005/06. Socioeconomic inequalities in CVD, stroke, IHD, risk factors [physical inactivity, arterial hypertension (AHT), diabetes mellitus (DM), smoking, obesity and psychological distress (Mental Health Inventory ≤ 52)], as well as the number of medical visits, were analyzed by SES (family income using the OECD modified equivalent scale) using odds ratio (confidence interval = 95%), and concentration curves and indices. Of the 21 807 individuals, 53.34% are female, aged between 35 and 74 with mean 54 ± 11 years. CVD, IHD, stroke, AHT, MD and obesity are associated with lower SES, smoking is associated with higher SES, while physical inactivity, number of medical visits and psychological distress showed no significant association with SES. Results suggest an association between lifestyle, morbidity and SES. They also demonstrate the need for comprehensive health strategies, involving health promotion and disease prevention, that incorporate individual, cultural and socioeconomic characteristics.

Pyogenic abscesses and parasitic diseases

Parasitic diseases which during their course in the host switch the immune system from a T helper 1 to a T helper 2 response may be detrimental to the host, contributing to granuloma formation, eosinophilia, hyper-IgE, and increased susceptibility to bacterial and fungal infections. Patients and animals with acute schistosomiasis and hyper-IgE in their serum develop pyogenic liver abscess in the presence of bacteremia caused by Staphylococcus aureus. The Salmonella-S. mansoni association has also been well documented. The association of tropical pyomyositis (pyogenic muscle abscess) and pyogenic liver abscess with Toxocara infection has recently been described in the same context. In tropical countries that may be an interesting explanation for the great morbidity of bacterial diseases. If the association of parasitic infections and pyogenic abscesses and/or fungal diseases are confirmed, there will be a strong case in favor of universal treatment for parasitic diseases to prevent or decrease the morbidity of superinfection with bacteria and fungi.

A historical perspective and prospects of biomedical research on parasitic diseases

We all hope that biotechnology will answer some social and economical unavoidable requirements of the modern life. It is necessary to improve agriculture production, food abundance and health quality in a sustainable development. It is indeed a hard task to keep the progress on taking into account the rational use of genetic resources and the conservation of biodiversity. In this context, a historical perspective and prospects of the biomedical research on parasitic diseases is described in a view of three generations of investigators. This work begins with a picture of the scientific progress on biomedical research and human health over the last centuries. This black-and-white picture is painted by dissecting current advancements of molecular biology and modern genetics, which are outlined at the meaning of prospecting achievements in health science for this new millenium.

Calcificações vasculares nos doentes em diálise : elo de ligação entre doença óssea e doença vascular

RESUMO: A presente dissertação para tese de doutoramento apresenta o desenvolvimento e a validação de um método simples e original para o diagnóstico de calcificações vasculares em doentes em diálise, utilizando um score semiquantitativo criado por nós e obtido em RX simples da bacia e das mãos, denominado score de calcifi cação vascular simples. Demonstramos que este score vascular simples é preditor de risco cardiovascular nos doentes em diálise. O score de calcificação vascular simples associou-se ainda à baixa densidade mineral óssea avaliada por dual energy X -ray absortiometry (DXA) no colo do fémur. Verifi camos igualmente que, em doentes em diálise, as calcifi cações coronárias quantifi cadas pelo score de Agatston e o score de calcifi cação vascular simples se associaram a um menor volume ósseo avaliado em biopsias ósseas. Estes trabalhos corroboram a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular nos doentes em diálise, e um dos elementos que contribuem para este elo de ligação podem ser as calcificações vasculares. Este score de calcificação vascular simples avalia calcifi cações em artérias de grande, médio e pequeno calibre, e inclui os dois padrões radiológicos de calcificação: calcificação linear, associada à calcifi cação da camada média da parede arterial, e calcificação irregular, associada à calcifi cação da camada íntima arterial1. Nos diferentes trabalhos por nós publicados demonstramos que as calcificações vasculares avaliadas por este método simples e barato permitem a identificação de indivíduos com elevado risco cardiovascular. Este score vascular associa -se a maior risco de mortalidade cardiovascular2, de mortalidade de causa global3, de internamentos cardiovasculares2, de doença ardiovascular2, de doença arterial periférica2,4,de calcifi cações valvulares5 e de rigidez arterial3. As guidelines KDIGO (Kidney disease: improving global outcomes), publicadas em 2009,sugerem que os doentes renais crónicos nos estadios 3 a 5, com calcificações vasculares e valvulares, devem ser considerados como apresentando o mais elevado risco cardiovascular6. A elevada mortalidade dos doentes renais crónicos não é totalmente explicada pelos fatores de risco tradicionais7. A organização KDIGO defende, desde 2006, a hipótese da existência de um elo de ligação entre a doença óssea e a doença vascular8. Esta ligação pode ser explicada pelas alterações do metabolismo mineral e ósseo e pela sua interação com as calcificações vasculares. Verificamos, nos nossos trabalhos, uma associação entre calcifi cações vasculares e doença óssea. O baixo volume ósseo diagnosticado por análise histomorfométrica de biopsias ósseas foi preditor de maior risco de calcificações vasculares avaliadas pelo score de calcifi cação vascular simples (dados apresentados nesta dissertação, no capítulo 6) e pelo score coronário de Agatston num grupo de doentes em diálise9. A contribuição original deste artigo9 foi considerada merecedora de um editorial feito pelo Dr. Gérard London10, investigador líder na área da calcificação vascular dos doentes renais crónicos e actual Presidente da EDTA (European Dialysis and Transplantation Association). Fomos também os primeiros a descrever uma associação independente e inversa entre a densidade mineral avaliada no colo do fémur por DXA (dual energy X -ray absortiometry) com calcificações vasculares avaliadas pelo score de calcificação vascular simples, com rigidez arterial avaliada por velocidade de onda de pulsocarotidofemoral e com doença arterial periférica diagnosticada por critérios clínicos11. Fomos igualmente os primeiros a mostrar uma correlação signifi cativa entre a densidade mineral óssea avaliada por DXA no colo do fémur, mas não na coluna lombar, com a espessura cortical avaliada por análise histomorfométrica em biopsia óssea12. O nosso estudo atribui pela primeira vez à DXA um papel no diagnóstico de porosidade cortical nos doentes em diálise. A utilidade da avaliação diferencial da densidade mineral óssea cortical e trabecular necessita ainda de ser confirmada em estudos prospectivos. Este achado inovador do nosso estudo foi mencionado pela ERBP (European Renal Best Practice) no comentário feito à posição da KDIGO que considera ser reduzida a utilidade da densidade mineral óssea nos doentes em diálise13. Dois dos trabalhos incluídos nesta dissertação foram referenciados nas guidelines KDIGO 2009 para avaliar a prevalência das calcificações vasculares (KDIGO 2009: Tabela suplementar 10, Fig. 3.6) e para validar a associação entre calcificações vasculares e mortalidade cardiovascular (KDIGO 2009: Tabela suplementar 12, Fig. 3.7)6. A inclusão destes nossos dois estudos nas referências destas guidelines, que utilizaram o exigente sistema GRADE (Grades of recommendation, assessment, development, and evaluation) na classificação e selecção dos estudos, valida o interesse científico dos nossos trabalhos. O diagnóstico de calcificações vasculares tem um interesse prático para os doentes renais crónicos. A presença de calcifi cações vasculares é um sinal de alerta para a existência de um elevado risco cardiovascular, e esta informação pode ser utilizada para modificar a terapêutica nestes doentes6. Diferentes métodos podem ser usados para diagnosticar calcificações vasculares nos doentes em diálise14,15. O score de calcificação vascular simples tem a vantagem da simplicidade e de poder ser facilmente interpretado pelo nefrologista, sem necessidade de um radiologista. A reprodutibilidade deste score já foi demonstrada por diferentes grupos em estudos nacionais e internacionais16-24. Nestes estudos foi demonstrado que as calcifi cações vasculares avaliadas pelo método criado por nós são preditoras de maior risco de eventos cardiovasculares16, de amputações dos membros inferiores17, de velocidade de onda de pulso18,19, de calcificações corneanas e conjuntivais20 e de calcifi cações coronárias21. Também foi demonstrada uma associação inversa entre o score de calcificação vascular simples com os níveis séricos de PTH21, com os níveis de 25(OH)vitamina D 22,23 e com os níveis de fetuína A19,24. Todos estes estudos, realizados por diferentes grupos, que utilizaram o score de calcificação vascular simples na sua metodologia, comprovam a facilidade de utilização deste score e a concordância de resultados atestam a sua reprodutibilidade e a utilidade na avaliação dos doentes renais crónicos. ---------------------------ABSTRACT: This thesis presents the development and validation of a simple and original method to identify vascular calcifications in dialysis patients, using a semi -quantitative score that we have created and that is obtained in plain X -ray of pelvis and hands. This score was named in different publications as “simple vascular calcifi cation score”. We have demonstrated that this score is a predictor of higher cardiovascular risk in dialysis patients. The simple vascular calcification score was also associated with lower mineral bone density evaluated by DXA in femoral neck. In hemodialysis patients coronary calcifications evaluated by the coronary Agatston score and by the simple vascular calcification score were associated with lower bone volume analysed in bone biopsies. These studies corroborate the hypothesis of the existence of a link between bone disease and vascular disease in dialysis patients and one of the elements of this link may be vascular calcifications. This simple vascular calcification score identifi es calcifications in large, medium and small calibre arteries and includes the two radiological patterns of arterial calcifi cation: linear calcification which has been associated with the calcifi cation of the media layer of the arterial wall and irregular and patchy calcification which has been associated with the calcifi cation of the intima layer of the arterial wall1. In the several studies that we have published we have demonstrated that vascular calcifications evaluated by this simple and inexpensive method allow the identification of patients with high cardiovascular risk. This simple vascular calcification score is an independent predictor of cardiovascular mortality2, all -cause mortality3, cardiovascular hospitalizations2, cardiovascular disease2, peripheral artery disease2,4, valvular calcifi cations5 and arterial stiffness3.KDIGO (Kidney Disease: Improving Global Outcomes) guidelines published in 2009 suggest that chronic kidney disease patients in stages 3 to 5, with vascular and valvular calcifications should be considered to be at the highest cardiovascular risk6. The high mortality of chronic kidney disease patients is not completely explained by the traditional risk factors7 and KDIGO group supports, since 2006, the hypothesis of the existence of a link between bone disease and vascular disease8.This link may be explained by the alterations of the bone and mineral metabolism and their interaction with development and progression of vascular calcifications. We have also verifi ed in our studies the existence of an association between vascular calcifications and bone disease. Low bone volume diagnosed by histomorphometric analysis of bone biopsies, in a group of dialysis patients, was independently associated with the simple vascular calcification score (data presented in this thesis,chapter 6) and with coronary calcifications evaluated by the Agatston score9. The original contribution of this article published in CJASN9 deserved a commentary in an Editorial written by Prof. Gérard London10 leader investigator in this area and current EDTA (European Dialysis and Transplantation Association) President. We were also the fi rst group to describe an independent and inverse association between bone mineral density evaluated in the femoral neck by DXA (dual energy X -ray absortiometry) with vascular calcifications evaluated by the simple vascular calcification score, with arterial stiffness evaluated by carotid-femoral pulse wave velocity and with peripheral artery disease diagnosed by clinical criteria11. We were also the first group to demonstrate a significant correlation between bone mineral density evaluated by DXA in femoral neck but not in lumbar spine, with cortical thickness evaluated by histomorphometric analysis of bone biopsy12. Our study has attributed to DXA, for the first time, a role in the diagnosis of cortical porosity in dialysis patients. The clinical utility of the differential evaluation of bone mineral density in cortical or trabecular bone needs, however, to be confi rmed in prospective studies. This original fi nding of our study was mentioned by ERBP (European Renal Best Practice) commenting the KDIGO position in relation with the reduced utility of bone mineral density evaluation in dialysis patients13. Two of the studies included in this thesis have been integrated in a group of studies selected as references by the KDIGO guidelines published in 2009 to evaluate the prevalence of vascular calcifications in CKD patients (KDIGO 2009: Supplementary Table 10, Fig. 3.6) and to corroborate the association between vascular calcifications and cardiovascular mortality (KDIGO 2009: Supplementary Table 12, Fig. 3.7)6. The inclusion of both studies as references in the KDIGO guidelines that have used the exigent GRADE system (Grades of Recommendation, Assessment, Development, and Evaluation) in the classifi cation and selection of studies, validates the scientifi c value of our studies. The diagnosis of vascular calcifi cations has a practical interest for chronic kidney disease patients. The presence of vascular calcifications is an alert sign to the existence of a high cardiovascular risk and this information may be used to modify the treatment of these patients6. Different methods may be used to detect the presence of vascular calcifications in dialysis patients14,15. The simple vascular calcifi cation score has the advantage of being simple, inexpensive and easily evaluated by the Nephrologist without the need for a Radiologist interpretation. The reproducibility of this method has already been demonstrated by other groups in national and international studies16 -24. It was demonstrated in those studies that vascular calcifi cations evaluated by the method created by us, predict higher risk of cardiovascular events16, higher risk of lower limbs amputations17, higher pulse wave velocity18,19, corneal and conjuntival calcifi cations 20 and coronary calcifi cations21. A negative association between the simple vascular calcification score and PTH levels21, 25(OH) vitamin D levels22,23 and Fetuin A levels19,24 has also been demonstrated. All these studies performed by different groups that have used the simple vascular calcifi cation score in their methods demonstrate that this score is simple, useful and reproducible in the evaluation of chronic kidney disease patients simple, useful and reproducible in the evaluation of chronic kidney disease patients.

Expression of cyclooxygenase enzymes and prostaglandin E2 receptors in inflammatory airway diseases

Dissertação para obtenção do Grau de Mestre em Genética Molecular e Biomedicina

Confluent peripheral multiple mononeuropathy associated to acute hepatitis B: a case report

A thirty three year-old, male patient was admitted at the Hospital of the São Paulo University School of Medicine, at the city of São Paulo, Brazil, with complaint of pains, tingling and decreased sensibility in the right hand for the last four months. This had progressed to the left hand, left foot and right foot, in addition to a difficulty of flexing and stretching in the left foot. Tests were positive for HBeAg, IgM anti-HBc and HBsAg, thus characterizing the condition of acute hepatitis B. The ALT serum level was 15 times above the upper normal limit. Blood glucose, cerebral spinal fluid, antinuclear antibodies (ANA) and anti-HIV and anti-HCV serum tests were either normal or negative. Electroneuromyography disclosed severe peripheral neuropathy with an axon prevalence and signs of denervation; nerve biopsy disclosed intense vasculitis. The diagnosis of multiple confluent mononeuropathy associated to acute hepatitis B was done. This association is not often reported in international literature and its probable cause is the direct action of the hepatitis B virus on the nerves or a vasculitis of the vasa nervorum brought about by deposits of immune complexes.

Desenvolvimento de um oxímetro de pulso e de um sensor de medição de pressão arterial

Dissertação para obtenção do Grau de Mestre em Engenharia Biomédica

Disposable immunosensor using a simple method for oriented antibody immobilization for label-free real-time detection of an oxidative stress biomarker implicated in cancer diseases

This work proposes a novel approach for a suitable orientation of antibodies (Ab) on an immunosensing platform, applied here to the determination of 8-hydroxy-2′-deoxyguanosine (8OHdG), a biomarker of oxidative stress that has been associated to chronic diseases, such as cancer. The anti-8OHdG was bound to an amine modified gold support through its Fc region after activation of its carboxylic functions. Non-oriented approaches of Ab binding to the platform were tested in parallel, in order to show that the presented methodology favored Ab/Ag affinity and immunodetection of the antigen. The immunosensor design was evaluated by quartz-crystal microbalance with dissipation, atomic force microscopy, electrochemical impedance spectroscopy (EIS) and square-wave voltammetry. EIS was also a suitable technique to follow the analytical behavior of the device against 8OHdG. The affinity binding between 8OHdG and the antibody immobilized in the gold modified platform increased the charge transfer resistance across the electrochemical set-up. The observed behavior was linear from 0.02 to 7.0 ng/mL of 8OHdG concentrations. The interference from glucose, urea and creatinine was found negligible. An attempt of application to synthetic samples was also successfully conducted. Overall, the presented approach enabled the production of suitably oriented Abs over a gold platform by means of a much simpler process than other oriented-Ab binding approaches described in the literature, as far as we know, and was successful in terms of analytical features and sample application.

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

In order to evaluate the potential allergenicity of Blomia tropicalis (Bt) antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT) as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.

Tratamento da Hipertensão Arterial nos Doentes com Obstrução Brônquica

A hipertensão arterial e a obstrução brônquica são doenças muito comuns na população, não sendo raro portanto que coexistam no mesmo indivíduo. É fundamental tratar cada uma delas sem agravar a outra. No que respeita ao tratamento anti-hipertensor existem de facto medicamentos que agravam ou causam obstrução brônquica pelo que devem ser usados com precauções acrescidas ou ser contra-indicados. Consideramos neste trabalho que na obstrução brônquica os anti-hipertensores indicados são os antagonistas do cálcio, os antagonistas serotoninérgicos, os diuréticos e os antagonistas alfa-1-adrenérgicos. Os anti-hipertensores contra-indicados são os antagonistas beta-adrenérgicos. Os anti-hipertensores a usar com precauções acrescidas são os inibidores do enzima de conversão da angiotensina e os agonistas alfa-2-adrenérgicos.

The Arterial Switch Operation in Europe for Transposition of the Great Arteries: a Multi-Institutional Study from the European Congenital Heart Surgeons Association

OBJECTIVES: This study analyzes the results of the arterial switch operation for transposition of the great arteries in member institutions of the European Congenital Heart Surgeons Association. METHODS: The records of 613 patients who underwent primary arterial switch operations in each of 19 participating institutions in the period from January 1998 through December 2000 were reviewed retrospectively. RESULTS: A ventricular septal defect was present in 186 (30%) patients. Coronary anatomy was type A in 69% of the patients, and aortic arch pathology was present in 20% of patients with ventricular septal defect. Rashkind septostomy was performed in 75% of the patients, and 69% received prostaglandin. There were 37 hospital deaths (operative mortality, 6%), 13 (3%) for patients with an intact ventricular septum and 24 (13%) for those with a ventricular septal defect (P < .001). In 36% delayed sternal closure was performed, 8% required peritoneal dialysis, and 2% required mechanical circulatory support. Median ventilation time was 58 hours, and intensive care and hospital stay were 6 and 14 days, respectively. Although of various preoperative risk factors the presence of a ventricular septal defect, arch pathology, and coronary anomalies were univariate predictors of operative mortality, only the presence of a ventricular septal defect approached statistical significance (P = .06) on multivariable analysis. Of various operative parameters, aortic crossclamp time and delayed sternal closure were also univariate predictors; however, only the latter was an independent statistically significant predictor of death. CONCLUSIONS: Results of the procedure in European centers are compatible with those in the literature. The presence of a ventricular septal defect is the clinically most important preoperative risk factor for operative death, approaching statistical significance on multivariable analysis.