Análises numérico-experimentais são fundamentais na simulação numérica do comportamento de alguns tecidos biológicos ou mesmo de sua interação com outras estruturas, como o que acontece entre artérias e stents. Simulações numéricas podem auxiliar no projeto da estrutura tubular ou na escolha do modelo de stent mais adequado para uma dada indicação clínica, bem como no aprimoramento da técnica cirúrgica de posicionamento. A obtenção de dados experimentais do comportamento mecânico de artérias é um desafio devido a fatores biológicos e experimentais, como a retirada da amostra, controle de temperatura e de umidade no armazenamento e manuseio dos corpos de prova. Outras dificuldades se apresentam na fixação da amostra e na realização de medições de deformação, além da mudança que pode ocorrer no tecido para diferentes indivíduos ou mesmo no mesmo indivíduo. Do ponto de vista numérico, é necessário um modelo de material capaz de reproduzir o comportamento experimental observado. O objetivo do presente trabalho é estudar problemas envolvidos na caracterização numérico-experimental de paredes arteriais para então propor uma metodologia apropriada para ser aplicada em uma amostra de aorta de um suíno da raça Landrace. Modelos numéricos adequados para simular o comportamento do tecido em sua região fisiológica de deformação foram estudados, e através dos dados obtidos de procedimentos experimentais foi realizada a identificação de parâmetros do modelo escolhido. / Numerical and experimental analyses are essential to understand the numerical simulation of the behavior of some biological tissues or even their interaction with other structures, such as what happens between arteries and stents. Numerical simulations can help in the tubular structure project or in the choice of the most suitable stent for a given clinical indication, as well as in the improvement of the surgical techniques in the positioning. The experimental data acquisition of arteries’ mechanical behavior is a challenge due to biological and experimental factors such as the removal of the sample, temperature and humidity control in the storage and handling of specimens. Other difficulties are the sample fixation and the strain measurements as well as the change that can occur in the tissue for different individuals or even in the same one. From the numerical point of view is necessary a material model capable to reproduce the observed experimental behavior. The objective of this work is to study the issues involved in the numerical and experimental characterization of arterial walls and then propose a suitable methodology to be applied in a pig's aorta sample of Landrace's breed. Numerical models suitable for simulating the behavior of physiological tissue deformation were studied and, through the data from experimental procedures, parameters were identified to represent it.

INTRODUÇÃO: Os pacientes que preenchem características clinicas, demográficas e/ou angiográficas de alto risco, quando submetidos a intervenções percutâneas, geralmente apresentam um baixo índice de sucesso e alta incidência de complicações isquêmicas agudas e de reestenose. A nossa hipótese é que, tratando este grupo de alto risco com o implante de Stents recobertos de heparina conseguiremos mudar favoravelmente esses índices. OBJETIVO: Comparar a incidência de reestenose angiográfica e de eventos cardíacos adversos maiores (ECAM), seis meses após a randomização, entre o implante de Stents recobertos de heparina e a angioplastia (ACTP) convencional em pacientes de alto risco. Secundariamente, comparar a incidência de ECAM durante hospitalização inicial e de eventos vasculares/hemorrágicos na fase hospitalar. MATERIAL E MÉTODOS: De 1053 intervenções realizadas entre janeiro de 1997 e dezembro de 1998, 68 Pc portadores de cardiopatia isquêmica grave e sintomática, foram randomizados para serem tratados com o implante de Stents (St) recobertos de heparina (n=35) ou com ACTP convencional (Ac) (n=33). Para serem incluídos no estudo, os pacientes deveriam apresentar, além de sintomas ou sinais de isquemia miocárdica grave, uma ou mais das seguintes características clínicas ou angiográficas: pacientes idosos (:?: 70 anos), portadores de diabete melito, angina instável (ou IAM em curso ou recente); classe funcional IH ou IV (da CCS), insuficiência cardíaca congestiva, disfunção sistólica do VE (FE < 40%), choque cardiogênico ou lesões tipo 132 ou C do ACC/ AHA. Os pacientes foram avaliados clinicamente no 1°, 3° e 6° mês pós-procedimento. No 6° mês (ou antes se necessário) foram submetidos a nova cinecoronariografm. RESULTADOS: Dos 68 Pc, 13,20/0 não completaram o seguimento clínico, a análise angiográfica fmal incluiu somente 59 Pc (29 e 30 para os grupos St e Ac respectivamente). O sucesso foi 91,40/0 e 84,80/0 para os grupos St e Ac (p=NS). A incidência de eventos cardíacos adversos maiores hospitalares para os grupos St e Ac respectivamente foram: mortalidade 2,90/0 vs. 0,00/0; IAM fatal e não fatal 8,60/0 vs. 12,1%; CRM de urgência ou nova intervenção 0,00/0 vs. 9,10/0. A análise combinada de ECAM nesta fase foi de 8,60/0 vs. 15,20/0 (p=NS). A incidência de hemorragia maior, hemorragia menor e as complicações vasculares foram semelhantes para ambos os grupos. A reestenose angiográfica foi 24,1% e 43,3% nos grupos St e Ac (p=0,2). As mudanças no diâmetro luminal mínimo (DLM) para os grupos St e Ac respectivamente foram: ganho inicial 1,89 ± 0,44 mm vs. 1,49 ± 0,49 mm (p=0,002); a perda em 06 meses foi em média de 0,55 ± 0,33 mm vs. 0,51 ± 0,23 mm (p=NS) e o ganho liquido fmal 1,34 ± 0,56 mm vs. 1,00 ± 0,62 mm (p=0,034). A análise combinada dos ECAM no fmal dos seis meses demonstrou uma diferença estatisticamente significativa favorecendo o grupo Stent (24,10A> vs. 53,3%, p=0,042). A taxa de incidência de revascularização (cirúrgica ou percutânea) foi 13,8% (grupo Stent) vs. 43,30/0 (grupo ACTP) (p=0,027). O índice de sobrevida livre de eventos em 06 meses foi significativamente mais alto no grupo Stent (75,9% vs. 46,70/0, p=0,042). CONCLUSÕES: A estratégia de implante de Stents heparinizados em pacientes de alto risco, seria uma alternativa satisfatória de tratamento, com índices de complicações semelhantes às da ACTP convencional, porém, acarretando uma adequada incidência de reestenose, uma diminuição significativa na taxa de eventos cardíacos adversos maiores, um menor índice de revascu1arização do vaso alvo e um aumento significativo na sobrevida livre de eventos, pelo menos nos primeiros seis meses do acompanhamento destes pacientes. / OBJECTIVES: This study sought to test the hypothesis that the treatment with heparin-coated stents in high-risk patients could change in a favourable way the restenosis rates and decrease the incidence of major adverse coronary events (MACE) at 6-month follow-up. BACKGROUND: Patients that fulfIll clinicaI, demographic and/or angiographic criteria for high risk when undergoing percutaneous coronary interventions (PCI) usually have a low success rate and both high acute ischemic complications and high restenosis rates. We postulate that treating this high-risk group of patients heparin-coated stents could change in a favourable way these rates and d(:;crease the major adverse coronary events (MACE) at 6-month follow-up. METHODS: We recruited 68 patients between January 1997 and December 1998 from 1053 who underwent PCI. Patients were random1y assigned to heparin-coated stent (ST) implantation (n=35) or balloon angioplasty (BA) (n=33). Patients were eligible for inclusion li they had symptoms or signs of myocardial ischemia and one or more of the following clinicaI and/or angiographic characteristic: age ~ 70, diabetes mellitus, unstable angina (or evolving AMI), 3-4 CCS score for angina, congestive heart failure, left-ventricular systolic dysfunction (EF < 400/0), cardiogenic shock, or type B2 or C lesions (ACC/ARA). ClinicaI follow-up was done at one, three and six months. At the six month a new corona:ry angiography was performed. RESULTS: From the original 68 patients 13.20/0 were lost to follow-up, so 59 patients were incIuded in the [mal angiographic analysis. Success rate was 91.40/0 vs 84.80/0 for ST and BA groups respectively (p=NS). The in-hospital cardiac event rates for both the ST and BA groups were: death 2.90/0 vs 0.0%; fatal and no-fatal AMI 8.60/0 vs 12.10/0; emergency CABO or PCI 0.00/0 vs 9.10/0. The in-hospital combined MACE rate was 8.60/0 vs. 15.20/0 (p=NS). The incidences of bleeding and/or vascular complications were similar in both groups. The angiographic restenosis rate was 24,1% vs. 43,3% in ST and BA groups respectively (p=0,2). The changes in minimalluminal diameter (MLD) for both ST and BA group were: acute gain 1,89 ± 0,44 mm vs. 1,49 ± 0,49 mm (p=0,002); 6-month mean 10ss 0,55 ± 0,33 mm vs. 0,51 ± 0,23 mm (p=NS) and net gain 1,34 ± 0,56 mm vs. 1,00 ± 0,62 mm (p=0,034). The late (6-month) MACE shown a significant statistical difference favorable to ST group (24,1% vs. 53,30/0, p=O,042). The late revascularization rate (surgical or PCI) for ST and BA groups was 13,8% vs. 43,30/0 (p=O,027). Finally, the 6-month event-free survival rate was significant higher in the ST group (75,9% vs. 46,70/0, p=O,042). CONCLUSIONS: Implanting heparin-coated coronary Stents in high risk patients seems to be a better approach of treatment, with complication rates similar to balloon angioplasty; however, it has a more reasonable restenosis rate, with a significant decrease in both major adverse coronary event and target vessel revascularization rates as well as a significant increase in event-free survival rates, during the 6-month follow-up period.

As temperaturas de transformações de fases são essenciais para trabalhar e caracterizar as ligas de NiTi, podendo-se assim, aproveitar de maneira eficiente suas propriedade de memória de forma e superelasticidade. O objetivo deste trabalho foi caracterizar as temperaturas de transformações de fases (As, Af, Ms, Mf, Rs, Rf) e a superfície de chapas e fios quanto a sua morfologia e a molhabilidade da liga NiTi submetidos a diferentes tratamentos térmicos para aplicação como órtese coronária. Tratamentos térmicos influenciam diretamente nas temperaturas de transformações de fases e na superfície do material, portanto os fios e chapas foram submetidos a diferentes tratamentos térmicos com diferentes tempos e temperaturas adquirindo diferentes colorações. Os fios foram submetidos a tratamentos térmicos de têmpera e temperaturas de 530 e 570°C, sendo analisados por DSC (Differencial Scanning Calorimeter), microscopia óptica e microdureza. Quando comparados com o fio sem tratamentos térmico mostraram mudanças nas temperaturas de transformações de fases. O fio com tratamento térmico de 570ºC apresentou as melhores temperaturas para aplicação como material biomédico. As superfícies dos fios foram analisadas por microscopia eletrônica de varredura (MEV), e devido ao seu diâmetro de 0,15 mm não foi possível analisar o material por microscopia de força atômica (AFM) e molhabilidade. As análises foram feitas em chapas com os mesmos tratamentos térmicos realizados nos fios para que se pudesse chegar a um resultado semelhante. Nas amostras de chapas os tratamentos térmicos variaram entre 500 (envelhecimento), 570 e 850°C e as temperaturas de transformação de fases foram analisadas por DSC e as superfícies por AFM, MEV e molhabilidade. As chapas com tratamento térmico de 500 e 570° C apresentaram temperaturas de transformação Af acima da temperatura corporal o que torna o material não indicado para aplicação como órtese (stent). A amostra 3 com tratamento térmico de 850° C não apresentou temperatura de transição martensítica. A análise de AFM teve como principal função escolher a rugosidade topográfica adequada ao ancoramento celular e revelou que a chapa azul foi a mais indicada em uso como órtese coronária. / The phases transformation temperatures are essential to work and to characterize the NiTi alloys and may thus take advantage efficiently its properties shape memory and superelastic. The objective of this study was to characterize the phase transformation temperatures (As, Af, Ms, Mf, Rs, Rf) and the surface of sheet and wires sufferes morphology and wettability of the NiTi alloy subjected to different heat treatments to application as a coronary stent. Heat treatments directly influence in the temperatures of phase transformations and on the material surface, so the wires and sheet were subjected to different heat treatments with different times and temperatures, getting different colors. The wires were subjected to heat treatments of 530 and 570 °C and analyzed by DSC (Differential Scanning Calorimeter), optical microscopy and microhardness. When compared with the wire without heat treatment showed changes in the temperatures of phase transformations. The blue color wire showed the best temperatures for application as biomedical materials. The wires surfaces were analyzed by scanning eletron microscopy (SEM) and due to its diameter of 0.15 mm was not possible to analyze the material by atomic force microscopy (AFM) and wettability. Therefore, the analyzes were performed in plates with the same heat treatments carried out on the wires so that it could reach to a similar result. In the plates the heat treatments ranged between 500 (aging), 570 and 850 °C and the phase transformation temperatures were analyzed by DSC and the surfaces by AFM , SEM and wettability. The plate with heat treatment to 500 °C showed the best phases transformation temperatures. The heat treatment sheet 500 and 570 °C to the temperature above the transformation temperature Af body which makes the material is not suitable for use as the prosthesis (stent). Sample 3 with heat treatment at 850 °C showed no martensite transition temperature. The AFM analysis had as main function choose the appropriate topographic roughness to the cellular anchor and revealed that a blue plate was the most suitable for use as a coronary stent.

Orientador: Marcelo Ganzarolli de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-08T04:10:36Z (GMT). No. of bitstreams: 1 Simoes_MairaMartinsdeSouzaGodoy_M.pdf: 3432819 bytes, checksum: d31e48f8632d109b7dba6dbd370c37f6 (MD5) Previous issue date: 2006 / Resumo: Stents são malhas metálicas expansíveis usadas em procedimentos de angioplastia, para a desobstrução das artérias coronárias. Atualmente há um grande interesse na obtenção de stents revestidos com matrizes poliméricas eluidoras de drogas que impeçam a reoclusão da artéria (reestenose). S-nitrosotióis doadores de óxido nítrico (NO) como a S-nitrosoglutationa (GSNO) possuem potencial para a inibição da reestenose. Neste trabalho, placas metálicas e stents foram revestidos com filmes de PVA contendo GSNO (107 µmol/g) através da imersão em soluções de PVA/GSNO com concentrações de PVA de 0,5 a 10,0% m/v. Filmes de PVA/GSNO foram submetidos a ciclos de congelamento/descongelamento (C/D), e analisados em relação ao seu grau de cristalinidade, dissolução, intumescimento, morfologia e propriedades de difusão e eluição da GSNO. Análises por DSC e difração de raios X, mostraram que o grau de cristalinidade do PVA aumenta com o número de ciclos de C/D, e com a secagem por sublimação do filme congelado. O aumento da cristalinidade se reflete em uma diminuição da velocidade de eluição da GSNO para a fase aquosa e da velocidade de dissolução e grau de intumecimento da matriz. Os coeficientes de difusão (D) da GSNO através de filmes de PVA foram medidos utilizando-se uma cela tipo Franz com monitoramento espectrofotométrico. Verificou-se que os valores de D são menores nos filmes secos por sublimação e submetidos a um ciclo de C/D. Este resultado foi atribuído ao aumento da densificação da fase amorfa, obtido na secagem por sublimação. Os filmes secos por esta técnica, apresentaram uma estrutura tridimensional esponjosa constituída por filamentos interligados, revelada por microscopia eletrônica de varredura (MEV). Estimou-se que stents revestidos com PVA/GSNO, a partir de soluções de PVA 0,5 % (m/v) esterilizados com óxido de etileno a 45-55°C podem liberar cerca de 30 µmoles/g de PVA para a parede arterial e levaram à obtenção de revestimentos sem filmes entre as hastes metálicas / Abstract: Stents are expansible wire mesh tubes used in angioplasty procedures in order to widening the luminal diameter of the coronary arteries. There is currently a great interest in the development of stents coated with drug-eluting polymeric matrices, which are able to prevent future closure of artery (restenosis). S-nitrosothiols which are nitric oxide (NO) donors, like S-nitrosoglutathione (GSNO) have potential to inhibit restenosis. In the present work, metallic plates and stents were coated with GSNO (107 µmol/g)- containing PVA films through their immersion in PVA/GSNO solutions with PVA concentration ranging from 0.5 to 10.0% wt/v. PVA/GSNO films were submitted to freezing/thawing cycles (F/T) and analyzed concerning their crystallinity dissolution, swelling, morphology and GSNO diffusion and elution properties. DSC and X Ray diffraction analysis have shown that the PVA crystallinity degree increases with the increase in the number of F/T cycles, and with the drying of the frozen film by sublimation. The increase in cristallinity was reflected in a decrease of the rate of GSNO elution to the aqueous phase, dissolution rate and swelling degree of the matrix. The diffusion coefficients of GSNO through PVA films were measured using a Franz-like cell with spectrophotometric monitoring. It was verified that D values are lower in the films dried by sublimation and submitted to one FT cycle. This result was attributed to the increase in the densification of the amorphous phase obtained in the drying by sublimation. The films dried by this technique, displayed a spongelike three-dimensional structure made by interconnecting filaments, revealed by scanning electron microscopy (SEM). Stents coated with PVA/GSNO, from solution of PVA 0.5 % (wt/v) have avoided the formation of films between the wires of the stent mesh. It was estimated that these stents are able to release ca. 30 µmols/g of PVA to the arterial wall after sterilization with ethylene oxide at 45-55 °C / Mestrado / Físico-Química / Mestre em Química

Introdução: Nas últimas décadas, a reestenose tem sido o \"calcanhar de Aquiles\" da intervenção coronária percutânea (ICP), limitando seus resultados no médio e longo prazo. Estudos preliminares demonstraram que após a injúria inicial com catéter balão e/ou com stents coronarianos, há desnudação endotelial, dissecção, deposição plaquetária e atração de leucócitos como resposta imediata, podendo levar à reestenose no seguimento mais tardio. A injúria local na parede arterial após implante de stent pode promover a expressão genética e liberação de mediadores inflamatórios, interleucinas, proteínas de fase aguda e fatores de coagulação, deposição de plaquetas e formação de trombos. Estes processos podem estar diretamente relacionados ao prognóstico da doença cardiovascular, porém são escassos os estudos que caracterizem a resposta inflamatória aguda pós-implante de stent coronariano e à ocorrência de eventos adversos. Objetivos: Neste estudo, pretendeu-se avaliar os efeitos de dose de ataque de Rosuvastatina (40mg) sobre a resposta inflamatória aguda após implante de stent coronariano, bem como correlacionar as variações das concentrações de citocinas e a respectiva expressão gênica. Métodos: Pacientes portadores de doença coronária estável sem uso de estatina (há mais de 7 dias), submetidos à intervenção coronária percutânea eletiva em artéria coronária nativa foram randomizados para receberem dose única de ataque de rosuvastatina (40 mg via oral, 3 horas prévias ao procedimento; Grupo Tratado (GT); n=63) versus Grupo Controle (GC) (Ausência da administração de rosuvastatina); n=61. Foram obtidas amostras do sangue periférico antes da administração via oral da medicação (A), 3 horas após medicação (B) e 3 horas após implante do stent coronariano (C). Avaliou-se hemograma completo, dosagem de proteína C reativa (PCR), óxido nítrico (NO) e análise da expressão dos genes e das proteínas, por meio de RT-qPCR e multiplex luminex, dos mediadores IL-1 ?, IL-6, IL-8, PAI-1, MCP- 1, TNF-? e TGF-?. Os pacientes foram acompanhados clinicamente por doze meses após o procedimento. Resultados: Os grupos não apresentaram diferenças significantes em relação às características clínicas, angiográficas e técnicas, com exceção da ICP para lesões em bifurcação, mais comum no GC (19,7% versus 6,2%; p=0,032). Para a expressão gênica, observou-se redução para IL-6 (p<0,001), da IL-1 ? (p=0,016) e PAI-1 (p=0,002) no Grupo Tratado. Para as interleucinas analisadas, observou-se uma diminuição progressiva nas concentrações de IL-6 0,209 pg/ml (IC 0,156;0,28 p<0,001), IL-1? 0,491 pg/ml (IC 0,349;0,692; p<0,001) e PAI-1 0,986 pg/ml com pinteração<0,001) no Grupo Tratado. Houve redução da concentração de PCR no tempo C no GT (p=0,04). Para o NO, ocorreu elevação dos valores do tempo A para C no Grupo Tratado (p=0,004). Na fase intra-hospitalar, ocorreu mais infarto periprocedimento entre os pacientes do Grupo Controle (23% vs 4,7%; p=0,004). No acompanhamento clínico de 12 meses ocorreram mais eventos combinados no Grupo Controle GC (9,8% vs 1,6%; p=0,058). Conclusão: Os resultados deste estudo demonstraram que a rosuvastatina em sua dose de ataque máxima preconizada (40mg), reduz os níveis séricos de marcadores inflamatórios agudos (IL-1 ?, IL-6, PAI-1 e PCR), com incremento dos valores de NO após ICP. / Restenosis remains as the \"Achilles\' heal\" of interventional cardiology, limiting the mid to long term efficacy of percutaneouos coronary interventions (PCI). Preliminary studies have shown that after initial injury with balloon catheter and/or metallic stents, there is endothelial denudation, dissection, platelet deposition and leukocyte attraction as an immediate response, which might limit the late benefits of PCI. Local injury to the arterial wall after stent implantation may promote the gene expression and release of inflammatory mediators, interleukins, acute phase proteins and coagulation factors, platelet deposition and thrombus formation, which are directly related to the prognosis of cardiovascular disease. Despite their importance, there are few studies that characterize the acute inflammatory response after coronary stent implantation and correlate it to the occurrence of adverse events.Objectives: We sougth to evaluate the effects of the loading dose of Rosuvastatin (40mg) on the acute inflammatory response after PCI with mettalic stents, as well as to correlate the variations in cytokine levels and their respective gene expression. Methods: Patients with stable coronary disease without statin (>=7 days) undergoing elective PCI to de novo lesions in the native coronary arterywere randomized to receive a loading dose of 40 mg of rosuvastatin [N = 63] versus a control group (CG) (absence of loading dose); [N = 61]. Blood samples were obtained prior to oral administration of the statin (A), 3 hours after medication (B) and 3 hours after PCI (C). The following laboratory tests were conducted: complete blood count, C-reactive protein (CRP), nitric oxide (NO) and analysis of gene and protein expression by means of RT-qPCR and multiplex luminex, IL-1 mediators, IL-6, IL-8, PAI-1, MCP-1, TNF-? and TGF-?. Clinical follow up was achieved up to 12 months after the procedure. Results: The groups did not significantly differ regarding clinical, angiographic and procedure characteristics, except for the higher amount of bifurcation lesions in the CG (19.7% versus 6.2%, p = 0.032). Among patients pre treated wit the statin, there was a reduction in gene expression for IL-6 (p <0.001), IL-1? (p = 0.016) and PAI-1 (p = 0.002). For the IL analyses, a progressive decrease in the concentrations of IL-6 0.209 pg / ml (IC 0.156; 0.28 p <0.001), IL-1? 0.491 pg / ml (IC 0.349; 0.692, p <0.001) and PAI-1 0.986 pg / ml with paving <0.001) were observed among patients treated with the statin. Furthermore, a progressive reduction in the concentration of CRP was observed in the three timepoints among patients of the rosuvastatin cohort (p = 0.04). An increase in NO concentration was observed from timepoint A to C in the statin group (p = 0.004). During the in hospital period, more periprocedural MI occurred among patients in the control group (23% vs 4.7%, p = 0.004). Also, 12-month MACE rate was higher in the control group (9.8% vs 1.6%, p = 0.058). Conclusion: Pre loading with high dose of rosuvastatin resulted in a marked reduction in the expression of the main inflammatory markers (IL-1 ?, IL-6, PAI-1 and CRP) associated with restenosis after PCI with stents. Additionally, an increase in the NO blood concentration and expression was noticed among these patients.

Introdução: Embora a intervenção coronária percutânea esteja associada a baixos índices de complicações, o infarto do miocárdio periprocedimento tem sido apontado como um fator negativo nos resultados clínicos. Os ensaios clínicos randomizados e as revisões sistemáticas recentes confirmaram que uma alta dose de estatina antes da intervenção coronária percutânea eletiva reduz o risco para a ocorrência do infarto do miocárdio periprocedimento. Objetivos: O objetivo desta pesquisa foi aferir a eficácia da pré-administração de uma dose de ataque de rosuvastatina na redução do infarto do miocárdio periprocedimento em pacientes submetidos à intervenção coronária percutânea eletiva com stent coronário. Métodos: De março de 2011 a dezembro de 2013, um total de 528 pacientes portadores de doença coronária estável em uso de estatina (há mais de 7 dias), submetidos à intervenção coronária percutânea eletiva em artéria coronária nativa (e lesão não reestenótica) foram randomizados prospectivamente em único centro, para receberem dose única de ataque de rosuvastatina (40 mg via oral, 2 a 6 horas prévio ao procedimento; grupo rosuvastatina; n=264) versus tratamento padrão (ausência da administração de rosuvastatina; grupo controle; n=264). O objetivo primário foi analisar a incidência intra-hospitalar de infarto do miocárdio periprocedimento (elevação da fração miocárdica da creatina-quinase massa maior que 3 vezes o limite superior do normal). Os objetivos secundários foram analisar a incidência da elevação da fração miocárdica da creatina-quinase massa acima de 1 vez o limite superior do normal e a incidência de eventos adversos graves como infarto agudo do miocárdio com supra desnível do segmento ST, revascularização emergencial do vaso-alvo (percutânea ou cirúrgica) e óbito intra-hospitalar. Resultados: O desfecho primário ocorreu em 7,6% dos pacientes tratados com rosuvastatina e em 4,8% no grupo controle (p = 0,200); ao consideramos o desfecho secundário (elevação da fração miocárdica da creatina-quinase maior que uma vez o limite superior do normal), verificamos que o grupo rosuvastatina apresentou mais desfechos quando comparado ao grupo controle (26,2% vs 18,4%, p = 0,039). Não houve diferença nos eventos adversos graves intra-hospitalar sendo 0% no grupo da rosuvastatina e 0,8% no controle devido a infarto agudo do miocárdio com supradesnível do segmento ST. Conclusões: Esta pesquisa sugere que a administração de dose de ataque de rosuvastatina prévio à intervenção coronária percutânea eletiva, em pacientes com doença coronária estável e em uso de estatina, aumenta a chance de elevação da fração miocárdica da creatina-quinase massa. Este efeito não foi significante para o desfecho primário (infarto do miocárdio periprocedimento) que foi pouco frequente neste estudo, mas foi significante para o desfecho secundário (elevação da creatina-quinase massa acima de 1 vez o limite superior do normal). As taxas de eventos clínicos adversos graves intra-hospitalar não foram afetadas pelo tratamento. / of complications, periprocedural myocardial infarction has been appointed as a negative factor in clinical outcomes. Randomized clinical trials and recent systematic reviews have confirmed that a high dose of statin before elective percutaneous coronary intervention reduces the risk of periprocedural myocardial infarction. Objectives: The objective of this study was to assess the efficacy of a loading dose of rosuvastatin pre-administration in reducing periprocedural myocardial infarction, in patients undergoing elective percutaneous coronary intervention with stable coronary artery disease on statin use for more than 7 days. Methods: From March 2011 to December 2013, a total of 528 patients with stable coronary artery disease on statin use (more than 7 days) who underwent elective percutaneous coronary intervention in native artery (and non restenosis lesion) were prospectively randomized in a single center to receive either a pre-procedural loading dose of Rosuvastatin (40 mg oral, 2 to 6 hours prior to the procedure; rosuvastatin group, n=264) or standard treatment (without administration of rosuvastatin; control group, n = 264). The primary endpoint was in-hospital stay incidence of periprocedural myocardial infarction (creatine kinase-myocardial band elevation greater than the three times the upper limit of normal). The secondary end points were in hospital stay incidence of creatine kinase-myocardial band elevation greater than once the upper limit of normal and the incidence of major adverse events as acute myocardial infarction with ST segment elevation, emergency target vessel revascularization (percutaneous or surgical) and death. Results: The primary end point occurred in 7.6% of patients treated with rosuvastatin loading dose and in 4.8% in the control group (p = 0.200); there was a higher incidence in elevation of post-procedural creatine kinase-myocardial band greater than once the upper limit of normal in the rosuvastatin group (26.2% vs 18.4%, p = 0.039). There were no differences in the rate of major adverse events with 0% in the rosuvastatin group and 0.8% in control driven by acute myocardial infarction with ST-segment elevation in hospital stay. Conclusions: This study suggest that loading dose of rosuvastatin prior to elective percutaneous coronary intervention, in patients with stable coronary disease on prior statin use increases the chance of creatine kinase-myocardial band elevation. This effect was not significant for the primary outcome (periprocedural myocardial infarction) that was uncommon in this study, but was significant for the secondary outcome (creatine-kinase elevation once the upper limit of normal). The rates of major adverse major events were not affected by treatment during hospital stay.

Abstract Biliary carcinoma, biliary fistula with occasional gallstone ileus and primary sclerosing cholangitis (PSC) are serious diseases and present specific diagnostic and therapeutic challenges. Stenting of biliary obstruction has also involved problems, but the reports are contradictory and partly limited. The aim of the present work was to evaluate and compare various imaging modalities in biliary diseases. The study also aimed to evaluate the usefulness of metallic stents in malignant biliary obstruction. The study population consisted of 210 patients with gallbladder carcinoma, bile duct carcinoma, biliary fistula, PSC or malignant biliary obstruction and eight control patients with various hepatobiliary diseases. The imaging findings of 80 patients with gallbladder carcinoma, 58 patients with bile duct carcinoma, and 16 patients with biliary fistula were reviewed. Nine patients with PSC underwent magnetic resonance cholangiography (MRC) and magnetic resonance imaging (MRI) of the liver, ultrasonography (US) of the liver and the bile ducts and endoscopic retrograde cholangiography (ERC). Eight control patients had had MRC and MRI of the liver and ERC. The medical records and radiographs of 39 patients with malignant biliary obstruction treated with percutaneously inserted metallic stents were also analysed. The stents included 48 Wallstents and seven Memotherm stents. In cases of gallbladder carcinoma, US visualised the primary tumour in 68 % and computed tomography (CT) in 57 % of the cases examined, but both methods were insufficient for accurate staging. In bile duct carcinoma, US revealed the primary tumour in 63 % and CT in 44 % of the cases examined. Both methods were sensitive in diagnosing peripheral intrahepatic cholangiocarcinoma, but inaccurate for more distal bile duct carcinoma or abdominal spread. The infiltrating type of gallbladder carcinoma and bile duct carcinoma were difficult to detect. US and CT were sensitive in revealing bile duct obstruction. The patients with biliary fistula and gallstone ileus had undergone various examinations with pathological, but not diagnostic results, and there was often a delay to diagnosis. Imaging did not reveal any of the ten spontaneous fistulas, but CT showed one of the five cases of gallstone ileus, and Gastrografin® meal revealed the single case of Bouveret's syndrome. Fistulography or cholangiography revealed all but one of the six iatrogenic fistulas. A nonvisualised or shrunken gallbladder at US should raise a suspicion of biliary enteric fistula in an appropriate clinical setting. MRC-MRI depicted the changes of PSC correctly in nine patients (radiologist 1) and in eight patients with one false positive finding (radiologist 2) in a blinded analysis. In the segmental comparison MRC missed especially bile duct dilatations. MRC was too pessimistic in the evaluation of the predictors of poor outcome. US detected features suggestive of PSC in eight patients (radiologist 3). US was unable to indicate the predictors of poor outcome. Of the patients with metallic stents in malignant biliary obstruction, 30 % had early and 66 % late complications, including stent obstructions, which occurred in 27 % of the patients at a mean of 4.4 months. The cause was mostly tumour ingrowth or overgrowth. The 25-week and 50-week patency rates were 71 % and 42 %. The patency rates of the patients with cholangiocarcinoma were significantly the lowest. There was also a tendency towards lower patency with less dilatation of the stents, an increasing number of the stents, longer strictures and hilar strictures. Many other complications were infectious. 31 % of the patients had late reinterventions.

Current economic evaluations do not explicitly acknowledge that there are multiple decision points throughout the lifecycle of new health technologies which, in the presence of uncertainty and irreversible consequences of those decisions, influence value. Real options analysis (ROA) has been proposed to overcome these limitations. However, applications to date all assumed that decisions influencing the arrival of information are made by the same actors making the decisions on adoption. The aim of this thesis is to explicitly incorporate into health technology assessment (HTA) the impact of uncertainty on decision making about new health technologies in the presence of irreversibilities. I present a series of analyses comparing “traditional” economic evaluation methods to applications of ROA using the case study of drug-eluting stents (DES). The conventional application of ROA allowed for flexibility in decisions incorporating all economic consequences of changing decisions. Over and above uncertainty surrounding the current estimate of value, three major components contributing to the economic value of the new technology were assumed to also change over time. This type of analysis can be used to determine the optimal initial decision allowing for changes in decisions and the optimal timing for review. However, it assumes that new information will always be revealed, regardless of the original decision on adoption. To reflect the combined impact of coverage, pricing and research decisions in HTA and therefore to make information arrival endogenous, a more complex approach is suggested: a Real Options Game (ROG) combining ROA with a game theoretical approach. In the ROG the HTA body and the manufacturer are assumed to play a sequential, incomplete information game, where the manufacturer has control over the arrival of information. The manufacturer decides whether to submit evidence, reduce price and conduct more research, while the HTA body decides on adoption. The DES analysis modelled a series of decision points between 2005 and 2010, with decisions not depending on hindsight, but allowing for predicted changes in value, incorporating a drift in information and responses by the other party. Payoffs were estimated for both players using a probabilistic Markov model. Optimal strategies incorporating the impact of earlier decisions on research were determined. HTA is a dynamic and interactive process, therefore results of the ROA analyses sometimes suggested a different course of action compared to traditional analyses. The best decision may depend on predictions of how other parties will react, as well as likely evolution of the evidence base and the costs of decision reversal.

No description available.

Lung cancer is the leading cause of cancer mortality and morbidity. Patients with advanced lung cancer have distressful symptoms like dyspnea. It has severe negative impact on the quality of life. Airway stenting has become widespread for palliation of airway stenosis in patients with metastatic airways disease. Although it provides improvement in symptoms, actual survival benefit is limited with severe potential complications. Appropriate patient selection in terms of site of tumor, type of stent placement is needed to achieve maximum benefit for patients. Here we will discuss 2 patients with advanced lung cancer who received bronchial stent for intractable dyspnea. Although there was dramatic improvement in symptoms and quality of life, both died shortly. Was there any benefit of stenting remained unanswered.