Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

Bladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70–75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.This study was supported by FCT (“Portuguese Foundation for Science and Technology”) through a PhD grant to RB (SFRH/ BD/111321/2015). Further funding was obtained from the project “Advancing cancer research: from basic knowledge to application” NORTE-01-0145-FEDER-000029: “Projetos Estruturados de I & D & I,” funded by Norte 2020—Programa Operacional Regional do Norte. This article is a result of the project PTDC/MED-ONC/31438/2017 (The Other Faces of Telomerase: Looking beyond Tumor Immortalization), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI) and by Portuguese funds through FCT. Further funding by the European Regional Development Fund (ERDF) through the Operational Programme for Competitiveness and Internationalisation— COMPETE 2020, and Portuguese national funds via FCT, under project POCI-01-0145-FEDER-016390:CANCEL STEM

Assessment of bone ingrowth potential of biomimetic hydroxyapatite and brushite coated porous E-beam structures

The bone ingrowth potential of biomimetic hydroxyapatite and brushite coatings applied on porous E-beam structure was examined in goats and compared to a similar uncoated porous structure and a conventional titanium plasma spray coating. Specimens were implanted in the iliac crest of goats for a period of 3 (4 goats) or 15 weeks (8 goats). Mechanical implant fixation generated by bone ingrowth was analyzed by a push out test. Histomorphometry was performed to assess the bone ingrowth depth and bone implant contact. The uncoated and hydroxyapatite-coated cubic structure had significantly higher mechanical strength at the interface compared to the Ti plasma spray coating at 15 weeks of implantation. Bone ingrowth depth was significantly larger for the hydroxyapatite- and brushite-coated structures compared to the uncoated structure. In conclusion, the porous E-beam surface structure showed higher bone ingrowth potential compared to a conventional implant surface after 15 weeks of implantation. Addition of a calcium phosphate coating to the E-beam structure enhanced bone ingrowth significantly. Furthermore, the calcium phosphate coating appears to work as an accelerator for bone ingrowth

The Risk of Exposure to Ionizing Radiation During Endovascular Procedures

Objectivos: Com a generalização dos procedimentos endovasculares, cresce a preocupação com os efeitos deletérios que a execução continuada de tais procedimentos radiológicos acarreta. Com este trabalho pretendeu-se avaliar e quantificar a distribuição pela equipa cirúrgica da exposição à radiação dispersa, emitida por um aparelho portátil de radioscopia com arco cirúrgico (arco em C), durante a utilização em bloco operatório. Material e métodos: O registo e avaliação da dose de radiação foram efectuados em sala do bloco operatório reproduzindo as condições habituais em que decorrem os procedimentos endovasculares. Para a simulação geométrica do tórax do doente foi utilizado um fantoma cilíndrico de polimetilmetacrilato (PMMA) com 15 cm de espessura. A radiação dispersa foi medida para o local do cirurgião, ajudante, anestesista e enfermeira instrumentista, através de um monitor de radiação portátil RaySafe Xi Survey Detector, tendo sido ajustada a medição para a avaliação da taxa de dose de exposição à radiação em mGy/s a diversas alturas do solo e distâncias do doente. Utilizou-se ainda o detetor RaySafe Xi R/F para a medição da taxa de dose de exposição na superfície de entrada da pele do doente. As medições foram efectuadas em modo de fl uoroscopia pulsada de 4 quadros por segundo (qps), subtração digital e roadmap, com a combinação dos três modos de magnifi cação electrónica disponíveis (Mag1, Mag2 e Mag3). Em todos os casos foi considerada a Dose 3, o nível de dose máxima do aparelho que fornece a melhor qualidade de imagem através do controlo automático em tempo real do contraste e do brilho. Resultados: A análise dos dados permitiu determinar a distribuição da radiação dispersa pela equipa assistente, constatando-se como nível máximo de exposição, a altura ao solo de 120 cm no modo de subtracção digital e roadmap. A este nível, a intensidade da radiação dispersa em relação à taxa de dose de exposição na superfície de entrada da pele do doente é distribuída em 0,47% pelo cirurgião, 0,21% pelo anestesista, 0,32% pelo ajudante e 0,13% pela enfermeira instrumentista. A utilização de subtração digital e roadmap aumentou o nível de radiação cerca de 5 vezes em relação à fluoroscopia pulsada a 4 qps, tanto na taxa de dose de exposição na superfície de entrada da pele do doente como na radiação dispersa pela equipa. Quando utilizados os meios de proteção radiológica os níveis de radiação foram consideravelmente inferiores. Conclusões: Atendendo à dispersão prevista da radiação determinou-se que a proximidade da ampola aumenta a quantidade de radiação dispersa que atinge o corpo. Quando utilizado o equipamento de proteção individual, os níveis de radiação dispersa são consideravelmente menores e permitem doses acumuladas abaixo dos limites aceitáveis

Surgical complications in 2000 renal transplants

INTRODUCTION: Renal transplantation is the best treatment for end-stage renal disease. In the last years, we have seen improvements in immunosuppressive treatment, which have allowed patients to experience a better quality of life and graft survival. Nevertheless, surgical complications remain important problems that increase morbidity, mortality, costs, and hospitalization. Our purpose was to evaluate surgical complications among a large series of 2000 renal transplantations. PATIENTS AND METHODS: We retrospectively analyzed all surgical complications among 2000 renal transplants performed between June 1980 and March 2010 in our department. RESULTS: Among 318 (15.9%) surgical complications, 4.8% of patients had urologic problems. Ureteral stenosis and fistula, stent obstruction, and ureteral necrosis occurred in 2.7%, 1.8%, 0.1%, and 0.2% of patients, respectively. Vascular complications reported in 2.7% of patients included arterial or venous thrombosis (1.0% or 0.4%), both arterial and venous thrombosis (0.1%), renal infarction (0.1%), renal artery aneurysm (0.1%) as well as arterial stenosis (0.5%), kinking (0.4%), or dissection (0.1%). Other complications, not specifically related with transplantation surgery, occurred in 4.4% of patients. CONCLUSION: Renal transplantation is a safe surgery by experienced teams. Our rates of surgical complications were within those reported by other series. A meticulous surgical technique is mandatory to prevent them. Prompt diagnosis and management are required to prevent graft damage and patient morbidity

What can a logistic regression model offer to a three-dimensional ergonomic study?

O modelo Ergonomic Tri-dimensional Analysis (ETdA) tem como objectivo principal analisar os factores de natureza ergonómica nas áreas comerciais com livre circulação de pessoas. As três dimensões que constituem o modelo: analista, profissional e clientes, são responsáveis pela avaliação desses factores da área em estudo. Para cada dimensão, foram desenvolvidos instrumentos de observação. A dimensão do profissional tem sido largamente estudada e explorada pelos modelos de análise ergonómica mais convencionais. A identificação e estabelecimento de múltiplas correlações na dimensão do cliente são, sem dúvida, um desafio na validação do modelo ETdA. A utilização da regressão logística contribuiu para a interpretação da análise funcional de dados provenientes da aplicação do questionário ETdA na dimensão do cliente. Considerou-se como principal objectivo do estudo a identificação dos factores de natureza ergonómica que influenciam o indivíduo em relação à sua preocupação com questões ergonómicas na concepção de espaços de trabalho. Como variável resposta utilizou-se a pergunta “Qual a importância que dá às considerações ergonómicas na concepção de espaços de trabalho?”. Após este pré-processamento foram utilizados 142 indivíduos para ajuste do modelo. Os indivíduos que avaliaram o risco de ocorrer algum acidente como sendo “possível” apresentam uma possibilidade 6,60 vezes maior de “dar importância” às considerações ergonómicas na concepção de espaços de trabalho. Os indivíduos que informaram que sentem alguma dificuldade em alcançar um produto exposto nas prateleiras apresentam uma possibilidade 3,09 vezes menor de “dar importância” nas considerações ergonómicas na concepção de espaços de trabalho. O modelo é aprovado nos testes de adequação global e as variáveis apresentam significância estatística, ao nível de significância de 5%. Estes factores de natureza ergonómica são importantes na concepção de espaços de trabalho e áreas subjacentes, no entanto, o conceito de ergonomia como ciência não pode ser tão redutor e limitativo.The Ergonomic Tri-dimensional Analysis model (ETdA) aims to analyze the ergonomic factors in the commercial areas with free circulation of people. The three dimensions that constitute the model: analyst, professional and clients, are responsible for the assessment of these factors in the study area. For each dimension, observation instruments were developed. The professional dimension has been widely studied and explored by the models of more conventional ergonomic analysis. The identification and the definition of multiple correlations for the client dimension is certainly a challenge in the validation of the ETdA model. A logistic regression analysis contributed to the functional analysis interpretation of the ETdA questionnaire data regarding the client dimension. It was considered as the main objective of the study the identification of the ergonomic factors that influencing the individual regarding to their ergonomic issues perception in the workspaces. "What is the importance that you give to the ergonomic considerations in the workspaces design?" was question used as the response variable. After the preprocessing, 142 individuals were used to fit the model. Individuals who assessed the risk of an accident to occur as "possible" presented 6.60 times more likely to "give importance" to ergonomic considerations in the workspaces design. People who refer to feel some difficulty in achieving a product displayed on shelves have 3.09 times less likely to "give importance" in ergonomic considerations in the workspaces design. The model was accepted in the global suitability tests and the variables have statistical significance (significance level of 5%). These ergonomic factors are important in design of workspaces and surrounding areas; however the ergonomic concept as a science cannot be simplistic and restrictive