Browsing by Author "Lima, Bruno A."
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- ANXA11 association with Sarcoidosis susceptibility: a meta-analysis of non-family-based studiesPublication . Lima, Bruno A.; Morais, António; Alves, HelenaSarcoidosis is a multisystemic disorder of unknown etiology, characterized by the formation of noncaseating granulomas, predominantly in the lungs and lymph nodes. The sarcoidosis association with the ANXA11 rs1049550 SNP has been previously reported in case–control studies. We carried out this meta-analysis in order to collect all the relevant studies to further clarify the association of ANXA11 SNP rs1049550 C/T (R230C variant) polymorphism with Sarcoidosis susceptibility. Relevant published data were retrieved through Medline, PubMed andWeb of Science pertaining to Sarcoidosis and ANXA polymorphisms. Odds ratios (OR) with 95 % confidence intervals (CI) were used to assess the strength of the association. Z test was used to determine the significance of the pooled OR. Statistical heterogeneity was measured using the Q statistic. The effect of heterogeneity was quantified using the I2-statistic. Visual inspection of asymmetry in funnel plots was conducted. Begg’s rank correlation method and Egger weighted regression method were also used to statistically assess the publication bias. Statistical analyses were performed with STATA12.0 software. A total of 6 studies, including 3297 sarcoidosis cases and 3346 healthy controls, were collected in this meta-analysis. For T vs. C, no heterogeneity (Q=4.79, p=0.44, I2=0.0%) was observed among individual estimates, and original data were combined using the fixed-effects model. For the total population, we found that ANXA11 T allele was less common in the Sarcoidosis group than in the control group and we obtained an effect summary OR=0.69, with a 95 % CI=0.64-0.74, and p<0.001, which shows a protective association of SNP rs1049550 T allele to sarcoidosis. Our comprehensive meta-analysis indicated that there is sufficient evidence to demonstrate a conclusive association between the ANXA11 SNP rs1049550 and sarcoidosis susceptibility.
- Applying virtual crossmatch approach in portuguese kidney transplantsPublication . Lima, Bruno A.; Mendes, Miguel; Alves, HelenaPresence of donor specific antibodies anti-human leukocyte antigen (HLA) is generally a contra-indication for transplantation and nowadays the identification of these antibodies are part of most pre-transplantation evaluations. In Portugal, the implemented protocol for the registration and maintenance of the active list for kidney transplant includes a complement-dependent cytotoxity (CDC) panel-reactive antibody (PRA) screening method, and Luminex technology for detecting and characterizing HLA alloantibodies. Under the current Portuguese kidney allocation system from deceased donors, implemented in August 2007, deceased donor kidneys are primarily allocated via ABO identical and time on dialysis with extra points to hyperimmunized patients, namely PRA CDC>50%. Additional risk for the candidate or transplant organ can be represented by a proposed calculated PRA (cPRA) based upon unacceptable HLA antigens detected by Luminex to which the patient has been sensitized. These unacceptable HLA antigens used to generate cPRA represents a ‘virtual’ crossmatch (XM). Sensitized patients are less likely to be matched with a suitable donor organ. Even after clearing the hurdle of procuring a living donor, it is still possible that this is not sufficient due to the likelihood of having a XM-positive. In these cases and in the presence of incompatible blood type between recipients and their intended living donors, kidney paired donation (KPD) can provide an answer by facilitating exchanges between willing donors’ kidneys. A national Portuguese KPD program, when realized, may prevent the current loss of a significant number of suitable living donors and reduce waiting list time for a deceased donor. An upgrade of a suggested point system in a Portuguese KPD program will be the use of cPRA instead of the values of PRA CDC. In Portugal, the virtual XM approach simply represents the optimization of an existing technique.
- Assessment of a Portuguese panel reactive antibody calculatorPublication . Lima, Bruno A.; Alves, HelenaCalculated panel-reactive antibody (cPRA) is an accurate measure for the definition of candidates’ immunization to a transplant. Based upon unacceptable HLA antigens to which the patient has been sensitized, cPRA is computed with HLA allelic and haplotypic frequencies from a pool of possible donors and represents the percentage of donors that express one or more of the antigens unacceptable for a given transplant candidate. The aim of this study is to compare cPRA values obtained from HLA frequencies of Portuguese donors with values obtained from cPRA calculators from international established sources.
- Atividade do transplante renal de 2003 a 2016: Portugal na União Europeia a 28Publication . Lima, Bruno A.; Alves, HelenaA diálise e o transplante de rim são as terapias de substituição renal disponíveis para doentes com insuficiência renal. Em comparação com a diálise, o transplante renal está associado com uma substancial redução do risco de mortalidade e de eventos cardiovasculares, bem como com melhorias clinicamente relevantes, da qualidade de vida dos doentes. O objetivo deste trabalho é o de comparar a atividade de transplantação renal em Portugal com a atividade dos restantes países da União Europeia no período entre 2003 a 2016. Este estudo tem por base a informação do Observatório Global em Doação e Transplantação, recolhida e produzida pela colaboração entre a Organização Mundial de Saúde e a Organización Nacional de Trasplante de Espanha, de onde recolhemos os dados disponíveis respeitantes aos 28 países da União Europeia. Depois de em 2009 Portugal ter sido o país da União Europeia com o maior número de transplantes de rim de dador cadáver pmh, em 2012 Portugal cai para o 7º lugar deste ranking, ocupando em 2014 a sua pior posição (9º lugar) desde 2003. Se no que diz respeito aos transplantes com dador cadáver, Portugal já conseguiu alcançar posições cimeiras no ranking apresentado, relativamente ao transplante com dador vivo as posições de Portugal têm sido apenas modestas.
- Evaluation of the Portuguese kidney transplant allocation system: comparative results from a simulationPublication . Lima, Bruno A.; Alves, HelenaThe distribution of such a scarce resource as deceased donor kidneys should be made by observing a balance between fairness, efficiency and flexibility. Before implementing a new kidney allocation system, these principles should be evaluated and assured objectively. In this article we compare the renal transplant donor-recipient pair selection system implemented in Portugal in 2007 with the Eurotransplant (ET) and United Kingdom (UK) systems. We simulated data for 500 waitlist kidney transplant candidates and 70 deceased donors. Each of the 70 donors was allocated to the best pair of listed candidates, taking into account the criteria of the three allocation systems under analysis. Subsequently, we compare the selected candidate’s groups to kidney transplant. The Portuguese organ allocation model selects candidates with a greater number of incompatibilities with the donor compared to the other two models. Under the Portuguese system’s rules, candidates have a greater age difference with the respective donors (median = 12.5 years) than those selected by the ET system (10 years) or the UK system (8 years). The Portuguese model selected more hypersensitized candidates (15%), but this difference was not statistically significant when compared to the percentage of hypersensitized patients selected by the ET model (10.7%). The Portuguese model has less equity than the other two models under analysis, since the observed disadvantages regarding the number of incompatibilities and age differences with the respective donor are not compensated for by the selection of patients with longer time on dialysis.
- Evolução da atividade de transplantação renal em Portugal: dados públicos de 2003 a 2015Publication . Lima, Bruno A.; Alves, HelenaPara doentes insuficientes renais, o transplante de rim, quando possível, é a terapia de substituição da função renal que garante uma menor mortalidade, a redução de problemas cardiovasculares e uma melhor qualidade de vida em comparação com a diálise, mesmo em doentes com idade avançada e com morbilidades. A análise sistemática de indicadores associados à actividade da transplantação renal permite a melhor caracterização e conhecimento dos problemas existentes. O objectivo deste trabalho é o de descrever a evolução da actividade de transplantação renal em Portugal com a informação de acesso livre que está disponível para análise. Este estudo tem por base a informação do Observatório Global em Doação e Transplantação, recolhida e produzida pela colaboração entre a Organização Mundial de Saúde e a Organización Nacional de Trasplantes, de onde recolhemos os dados disponíveis respeitantes a Portugal, para os anos entre 2003 e 2015. No período em análise verificamos que 2009 foi o ano que registou um maior número de transplantes renais. Em 2012 registou- se a maior queda do número de transplantes de rim com dador cadáver (-20.8%) em relação ao ano predecessor. Só com a disponibilização de dados para análise é possível fazer o melhor escrutínio de políticas a implementar.
- Hypersensitized candidates to kidney transplantation in PortugalPublication . Lima, Bruno A.; Miguel, Mendes; Alves, Helena[ENG] The presence of donor specific anti-HLA antibodies is generally a contraindication for transplantation and nowadays the identification of these antibodies are part of most pre-transplantation evaluations. In Portugal, the implemented protocol for registration and maintenance of the active list for kidney transplant includes a complement -dependent cytotoxity (CDC) panel-reactive antibody (PRA) screening method, and Luminex technology for detecting and characterizing HLA alloantibodies. Under the current Portuguese kidney allocation system from deceased donors, implemented in August 2007, deceased donor kidneys are primarily allocated via ABO identical and time on dialysis with extra points to hyperimmunized patients, namely PRA CDC > 50%. Additional risk for the candidate or transplant organ can be represented by a proposed calculated PRA (cPRA) based upon unacceptable HLA antigens detected by Luminex to which the patient has been sensitized. These unacceptable HLA antigens used to generate cPRA represents a virtual crossmatch (XM). Sensitized patients are less likely to be matched with a suitable donor organ. Even after clearing the hurdle of procuring a living donor, it is still possible that this is not sufficient due to the likelihood of having an XM-positive. In such cases, and in the presence of incompatible blood type between recipients and their intended living donors, kidney paired donation (KPD) can provide an answer to this catch by facilitating exchanges between willing donors kidneys. A national Portuguese KPD programme, when realized, may prevent the current loss of a significant number of suitable living donors and reduce waiting list time for a deceased donor. An upgrade of a suggested point system in a Portuguese KPD programme will be the use of cPRA instead of the values of PRA CDC. In Portugal, the virtual XM approach just represents the optimization of an existent technique.
- Kidney allocation rules simulatorPublication . Lima, Bruno A.; Henriques, Teresa S.; Alves, HelenaThe greatest challenge of any kidney transplant program lies in finding enough organ donors (in number and quality) for all waitlisted transplant candidates. Unfortunately, we must resign ourselves to a manifestly insufficient supply of organs for the current demand. Furthermore we must be able to predict kidney transplant success at organ allocation if we want to minimize the number of patients who return to an already overcrowded waiting list for transplantation. Therefore, the definition of deceased donors' kidney allocation rules on transplantation must be supported by simulations that allow foreseeing, as much as possible, the consequences of these rules. Here we present the Kidney Allocation Rules Simulator (KARS) application that enables testing different kidney transplant allocation' systems with different donors and transplant candidates' datasets. In this application, it is possible to simulate allocation rules implemented in Portugal, in the United Kingdom, in countries within Eurtotransplant, and a previously suggested color priority system. As inputs, this application needs three data files: a file with transplant candidates' information, a file with candidates' anti-HLA antibodies, and a file with donors' information. As output, we will have a file with donor-recipient pairs selected according to the kidney allocation system simulated. When seeking waste reduction while ensuring a fair distribution of organs from deceased donors, the definition of rules selecting donor-recipient pairs in renal transplantation must be based on evidence supported by data. On the continuously changing process for a better distribution of an increasingly scarce resource must, we must be able to predict transplant outcomes when defining the best allocation rules.
- Measuring access to Kidney transplantationPublication . Lima, Bruno A.; Mendes, Miguel; Alves, HelenaKidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs, and the principle of justice by its effectiveness ensuring that all patients have a reasonable opportunity to be transplanted. The survival benefit of transplant patients when compared with dialyzed values is well described even after adjusting for age, comorbidities, albumin and Body Mass Index (BMI). This benefit is also observed in patients over the age of 60 years. Several factors are related to transplant efficiency: maximization of HLA matching for patients that are more relevant (children and youth), preference for children; minimization of ischemia time, and the relation of life expectancy of the graft with life expectancy of the receptor. The factors related to justice are: reduction of waiting times, and greater equity of access for patients regardless of their race, blood group, HLA homozygosity and geographic location. There are socio-demographic and immunological factors associated with longer waiting time for kidney transplantation, such as: age, blood group or sensitization against HLA antibodies.Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant candidates’ demographic factors such as: sex, age groups, socioeconomic status, clinical and immunological characteristics: blood group, PRA values, BMI, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programs. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait listed patients each year. By using the Cox regression analysis, with time on dialysis to transplantation as a dependent variable and clinical and socio-demographic factors as independent variables, will shed light on which characteristics most affect the access to transplantation. Only by defining and applying standardized metrics to kidney transplant candidates over time, is it possible to make informed decisions when debating organ allocation rules. “What gets measured gets improved”.
- Measuring kidney transplantation activityPublication . Lima, Bruno A.; Mendes, Miguel; Alves, Helena[ENG] Kidney allocation from cadaveric donors must balance two main principles: medical utility and justice. The principle of medical benefit is gauged by maximizing efficiency in the use of organs and the principle of justice by its effectiveness, ensuring that all patients have a reasonable opportunity of transplantation. In this paper we present some metrics that, when applied to candidates for kidney transplantation, will help in the best judgment defining kidney allocation systems. Knowing the prevalence and incidence (per year, per million inhabitants) of kidney transplant, candidates demographic factors, such as: sex, age groups, and socioeconomic status; as well as clinical and immunological characteristics: blood group, Panel Reactive Antibody values, Body Mass Index, type of dialysis, cause of renal failure, and comorbidities; allows for an objective comparison of allocation programmes. The waiting time for transplantation should be measured as the median time between the start of dialysis and transplantation of wait -listed patients each year. By using the Cox regression analysis, with time on dialysis for transplantation as a dependent variable and clinical, socio -demographic factors as independent variables, we will shed light on which characteristics affect the access to transplantation.