京都大学 / 新制・課程博士 / 博士(社会健康医学) / 甲第23822号 / 社医博第122号 / 新制||社医||12(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 木村 剛, 教授 西浦 博, 教授 長尾 美紀 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

Yes / This study aimed to determine whether a reduction in radiation dose was found for percutaneous coronary interventional (PCI) patients using a cardiac interventional x-ray system with state-of-the-art image enhancement and x-ray optimization, compared to the current generation x-ray system, and to determine the corresponding impact on clinical image quality. Patient procedure dose area product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray system were compared using a Wilcoxon test on median values. Significant reductions in patient dose (p ≪ 0.001) were found for the new system with no significant change in fluoroscopy duration (p ¼ 0.2); procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and “cine” acquisition DAP by 76%. The image quality of 15 patient angiograms from each x-ray system (30 total) was scored by 75 clinical professionals on a continuous scale for the ability to determine the presence and severity of stenotic lesions; image quality scores were analyzed using a two-sample t -test. Image quality was reduced by 9% (p ≪ 0.01) for the new x-ray system. This demonstrates a substantial reduction in patient dose, from acquisition more than fluoroscopy imaging, with slightly reduced image quality, for the new x-ray system compared to the current generation system. / This research was funded by Philips Healthcare (the Netherlands)

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25164号 / 医博第5050号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 石見 拓, 教授 大鶴 繁, 教授 江木 盛時 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

OBJECTIVES The aim of this analysis was to assess the 7-year long-term safety and effectiveness of a randomized comparison of percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) versus minimally invasive direct coronary artery bypass (MIDCAB) surgery for the treatment of isolated proximal left anterior descending lesions. BACKGROUND Long-term follow-up data comparing PCI by SES and MIDCAB surgery for isolated proximal left anterior descending lesions are sparse. METHODS Patients were randomized either to PCI with SES (n ¼ 65) or MIDCAB (n ¼ 65). Follow-up data were obtained after 7 years with respect to the primary composite endpoint of death, myocardial infarction, and target vessel revas- cularization. Angina was assessed by the Canadian Cardiovascular Society classification and quality of life with Short Form 36 and MacNew quality of life questionnaires. RESULTS Follow-up was conducted in 129 patients at a median time of 7.3 years (interquartile range: 5.7, 8.3). There were no significant differences in the incidence of the primary composite endpoint between groups (22% PCI vs. 12% MIDCAB; p ¼ 0.17) or the endpoints death (14% vs. 17%; p ¼ 0.81) and myocardial infarction (6% vs. 9%, p ¼ 0.74). However, the target vessel revascularization rate was higher in the PCI group (20% vs. 1.5%; p < 0.001). Clinical symptoms and quality of life improved significantly from baseline with both interventions and were similar in magnitude between groups. CONCLUSIONS At 7-year follow-up, PCI by SES and MIDCAB in isolated proximal left anterior descending lesions yielded similar long-term outcomes regarding the primary composite clinical endpoint and quality of life. Target vessel revascularization was more frequent in the PCI group. (Randomied Comparison of Minimally Invasive Direct Coronary Artery Bypass Grafting and Percutaneous Coronary Intervention With Drug-Eluting Stents in Patients With Proximal Stenosis of the Left Anterior Descending Coronary Artery; NCT00299429) (J Am Coll Cardiol Intv 2014;-:-–-) © 2014 by the American College of Cardiology Foundation.

Thesis (MScEng)--Stellenbosch University, 2012. / ENGLISH ABSTRACT: In percutaneous procedures, where the surgeon inserts a needle into a target in the patient, it is challenging to access the target at the rst attempt. Repeated needle insertion attempts are highly undesirable, as they lead to increased theatre time, patient haemorrhage and radiation exposure. The proposal of this thesis was to develop a low-cost system to aid surgeons with the process of positioning and orientating the needle prior to insertion. The proposed system uses a stereo pair of images produced by a standard C-arm uoroscope. By applying computer vision techniques, such as triangulation, the desired needle position and orientation are determined from the set of images. An articulated manipulator is used to position and orientate the needle. The surgeon makes selections on the images, via a graphical user interface (GUI), to indicate the desired position and orientation of the needle. Following these selections, an algorithm determines the necessary angles for the manipulator. The surgeon then positions the manipulator accordingly. Results from tests on a phantom showed the system to be repeatable and accurate to 2 mm. This is less accurate than similar, existing systems which, reported accuracies of 0:25 and 1:21 mm. However, 2 mm accuracy is considered adequate as it allows a range of percutaneous procedures to be performed such as needle biopsy, regional anaesthesia, brachytherapy and percutaneous nephrolithotomy (PCNL). Tests on both a phantom kidney and a porcine kidney indicated that the system can function in a real percutaneous procedure and with an anatomical target. The total cost to develop the prototype system was R15 000. The accuracy of the proposed system and the time to gain access to the target indicate that the system can be a bene cial aid to surgeons when performing percutaneous procedures. As minimal X-ray imaging is required, patients will also be spared excessive radiation exposure and theatre time. / AFRIKAANSE OPSOMMING: In perkutane prosedures, waar die chirurg 'n naald in 'n teiken op die pasiënt invoeg, is dit moeilik om met die eerste probeerslag toegang tot die teiken te bekom. Herhaalde pogings om die naald in te voeg is hoogs ongewens, aangesien dit tot verlengde teatertyd, bloeding by pasinte sowel as stralingsblootstelling lei. 'n Laekostestelsel is ontwikkel om chirurge by te staan met die proses om die naald voor invoeging te plaas en te oriënteer. Die stelsel gebruik 'n paar stereobeelde wat deur 'n standaard-C-arm- uoroskoop voortgebring word. Met behulp van rekenaarsigtegnieke, soos triangulasie, word die gewenste naaldposisie en -oriëntasie uit die stel beelde bepaal. 'n Geartikuleerde manipuleerder word gebruik om die naald te plaas en te oriënteer. Die chirurg voer die vereiste invoerdata deur middel van 'n gra ese gebruikerskoppelvlak (GGK) in, waarna 'n algoritme die vereiste hoeke vir die manipuleerder bepaal. Die chirurg plaas dan die manipuleerder dienooreenkomstig. Die resultate van toetse op 'n fantoom toon dat die stelsel herhaalbaar en tot op 2 mm akkuraat is. Dit is minder akkuraat as soortgelyke, bestaande stelsels, wat 'n akkuraatheid van 0:25 mm en 1:21 mm onderskeidelik aangemeld het. Tog kan akkuraatheid van 2 mm as voldoende beskou word, aangesien dit 'n verskeidenheid perkutane prosedures moontlik maak, soos naaldbiopsies, regionale anestesie, bragiterapie en perkutane nefrolitotomie (PCNL). Toetse op 'n fantoomnier dui daarop dat die stelsel wél in 'n werklike perkutane prosedure kan funksioneer. Toetse op 'n varknier toon dat die stelsel wél ook met 'n anatomiese teiken kan werk. Die totale koste om die prototipe te ontwikkel was R15 000. Die akkuraatheid van die voorgestelde stelsel en die tydsduur om toegang tot die teiken te bekom, dui daarop dat die stelsel 'n nuttige hulpmiddel kan wees vir chirurge wat perkutane prosedures uitvoer. Aangesien minimale Xstraalbeelding vereis word, sal dit pasiënte ook oormatige stralingsblootstelling en verlengde teatertyd spaar.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease associated with high levels of tumour necrosis factor-alpha (TNF-a) in synovial fluid and synovial tissue (Saxne et al., 1989). Thalidomide is a proven inhibitor of the biological synthesis of TNF-a (Sampaio et al., 1991) and is believed to rely on this action for its suppression of the wasting of tissue which accompanies RA. Oral administration of thalidomide has proven to be effective in RA, but unacceptable side effects are easily provoked (Gutierrez-Rodriguez, 1984). Administration of thalidomide via the dermal route can down-regulate TNF-a production in and around the affected joint, and this without raising the systemic blood level to a problematical level. Based on thalidomide's physicochemical properties, it is unlikely that it can be delivered percutaneously at a dose required for RA. Therefore, we have embraced the idea of using N-alkyl analogues of thalidomide. The most important feature that an analogue of this compound might contribute is decreased crystallinity and increased lipophilicity. Ordinarily both these parameters should favour percutaneous delivery. The current study was primarily aimed at exploring the feasibility of percutaneous delivery of thalidomide and subsequently, three of its odd chain IV-alkyl analogues (methyl, propyl and pentyl) via physicochemical characterization and assessment of their innate abilities to diffuse through skin as an initial step towards developing a topical dosage form for the best compound. The biological activities, more specifically their potential to inhibit the production of TNF-a was determined for thalidomide and its N-alkyl analogues. In order to achieve the objectives, the study was undertaken by synthesizing and determining the physicochemical parameters of thalidomide and its N-alkyl analogues. A high level of crystallinity is expressed in the form of a high melting point and heat of fusion. This limits solubility itself, and thus also sets a limit on mass transfer across the skin. Generally, the greater a drug's innate tendency to dissolve, the more likely it is that the drug can be delivered at an appropriate rate across the skin (Ostrenga et al., 1971). Therefore, the melting points and heats of fusion were determined by differential scanning calorimetry. Aqueous solubility and the partition coefficient (relative solubility) are major determinants of a drug's dissolution, distribution and availability. N-octanollwater partition coefficients were determined at pH 6.4. Solubilities in water, a series of n-alcohols and mixed solvents were obtained, as well as the solubility parameters of the compounds in study. Secondly, in vitro permeation studies were performed from these solvents and vehicles using vertical Franz diffusion cells with human epidermal membranes. Thirdly, tumour necrosis factor-alpha (TNF-a) inhibition activities were assessed for thalidomide and its N-alkyl analogues. By adding a methyl group to the thalidomide structure, the melting point drops by over 100°C and, in this particular instance upon increasing the alkyl chain length to five -CH2- units the melting points decrease linearly. Heats of fusion decreased dramatically upon thalidomide's alkylation as well. Methylation of the thalidomide molecule enhanced the aqueous solubility 6-fold, but as the alkyl chain length is further extended from methyl to pentyl, the aqueous solubility decreased exponentially. The destabilization of the crystalline structure with increasing alkyl chain length led to an increase in lipophilicity and consequently an increase in solubility in nonpolar media. Log partition coefficients increased linearly with increasing alkyl chain length. Solubilities in a series of n-alcohols, methanol through dodecanol, were found to be in the order of pentyl > propyl > methyl > thalidomide. The N-alkyl analogues have more favourable physicochemical properties than thalidomide to be delivered percutaneously. The in vitro skin permeation data proved that the analogues can be delivered far easier than thalidomide itself. N-methyl thalidomide showed the highest steady-state flux through human skin from water, n-alcohols and combination vehicles. Thalidomide and its N-alkyl analogues were all active as TNF-a inhibitors. Finally, active as a TNF-a inhibitor, N-methyl thalidomide is the most promising candidate to be delivered percutaneously for treatment of rheumatoid arthritis, of those studied. / Thesis (PhD (Pharmaceutics))--PU for CHE, 1999.

FUNDAMENTOS: Com a expressiva ampliação do uso dos stents farmacológicos (SF), nos diversos cenários em que se apresenta a doença arterial coronária (DAC), e diante de todas as evoluções das diferentes formas de tratamento, levantou-se o questionamento sobre a propriedade de indicação da intervenção coronária percutânea (ICP), à busca do discernimento sobre quais pacientes (P) com DAC apresentam o melhor balanço risco/benefício. Visando a sistematizar as indicações para procedimentos de RM, e tomando como referência as Diretrizes Internacionais baseadas nos principais estudos e ensaios clínicos desta área, em 2009, pela primeira vez, ACC/AHA/SCAI/AATS publicaram um documento sugerindo, frente aos diversos cenários clínicos e anatômicos da DAC, critérios de propriedade de indicação para os procedimentos de RM, permitindo classificá-los quanto à indicação em: A - apropriado, PA - pode ser apropriado ou RA - raramente apropriado. OBJETIVOS: O objetivo primário foi avaliar o grau de propriedade de indicação da ICP com SF nos pacientes do Registro DESIRE, no período de Janeiro de 2012 a Dezembro de 2013, correlacionando com a ocorrência de eventos cardíacos maiores (ECAM) (óbito, infarto e revascularização da lesão-alvo), num seguimento clínico de dois anos. Os objetivos secundários foram: comparar o grau de propriedade de indicação da ICP entre pacientes com apresentação clínica estável versus aqueles com síndrome coronária aguda (SCA); e a ocorrência isolada de óbito cardíaco (OC), infarto agudo do miocárdio não-fatal (IM), revascularização da lesão-alvo (RLA) e trombose do stent no período de follow-up. CASUÍSTICA E MÉTODOS: Foram incluídos todos os pacientes, consecutivamente tratados no HCor-ASS com ICP e implante de pelo menos um SF, entre 01/01/2012 a 31/12/2013. A coleta de dados foi feita do banco de dados do Registro DESIRE, em cujo programa constam dados pormenorizados das características clínicas, angiográficas e informações técnicas da intervenção, incluindo complicações, de cada um dos P registrados, além dos dados evolutivos obtidos nos períodos definidos após o procedimento-índice (1, 6, 12 meses e anualmente a partir de então). Fez-se a validação desses critérios, usando-se o aplicativo SCAI-QIT®, que permite a definição, ao serem incluídas as variáveis do P, do grau de propriedade de indicação para o implante do SF. Este aplicativo é facilmente acessado via internet, no seguinte site: http://scai-qit.org/. Após ser feita a classificação dos critérios de propriedade de indicação, os dados foram analisados estatisticamente, para obtenção dos objetivos e resultados do estudo em questão. RESULTADOS: Dentre os 1.108 P do Registro DESIRE analisados, usando-se o aplicativo SCAI-QIT®, observou-se que: 375 (33,8%) tiveram indicações Apropriada (Grupo I); 480 (43,3%) tiveram indicação Pode Ser Apropriada (Grupo II) e 215 (19,4%) tiveram indicação Raramente Apropriada (Grupo III). No Grupo I, 22,7% tinham isquemia silenciosa, 13,3% angina estável, 36,8 % SCAssST e 27,2% SCAcsST. No Grupo II, 34,0% tinha isquemia silenciosa, 11,9% angina estável, 33,3% SCAssST e 20,8% SCAcsST. No Grupo III, 82,3% tinham isquemia silenciosa, 4,2% angina estável, 0% SCAssST e 13,5% SCAcsST. A ocorrência de IM (definido como aumento da CKMB massa >3X o percentil 99) foi de 9,6%, 9,6%% e 7,0% (p= 0,652) nos Grupos I, II e III, respectivamente. A RLA foi de 1,9%, 2,1% e 0,9% (p= 0,592) e a taxa de trombose do stent foi 0,3%, 0,6% e 1,4% (p=0,406). Comparando os 3 grupos não foi estatisticamente significativo as taxas de OC e ECAM no follow-up de 2 anos. CONCLUSÕES: Os resultados deste estudo demonstram que apesar das taxas de PCI em pacientes estáveis e instáveis, destoarem das esperadas e das já documentadas, isso não teve relevância nos eventos maiores e sobrevida dos pacientes no follow-up clínico. / BACKGROUND: With the significant expansion of the use of drug-eluting stents in different scenarios as presented coronary artery disease (CAD), and before all the developments of different forms of treatment, rose the questioning on the indication of ownership of percutaneous coronary intervention (PCI), the pursuit of insight into which patients (P) with CAD have the best balance risk/benefit. Aiming to systematize indications for coronary revascularization procedures, and by reference to the International Guidelines based on the main studies and clinical trials in this area, in 2009 for the first time, ACC/AHA/SCAI/AATS published a paper suggesting, compared to various clinical and anatomical scenarios of CAD, criteria for appropriate indication of coronary revascularization procedures, allowing to classify them as the indicated in: A - Appropriate, PA - May be appropriate or RA - Rarely appropriate. OBJECTIVES: The primary objective was to evaluate the degree of appropriateness of the ICP with pharmacological stents in patients of DESIRE Registry, in the period from January 2012 to December 2013, correlating with the occurrence of major cardiac events (MACE)(death, myocardial infarction and target vessel revascularization), in the clinical follow-up of two years. The secondary objective were: to compare the degree of appropriateness of PCI indication among patients with clinical presentation satble versus those with acute coronary syndrome to isolated occurrence of cardiac death, myocardial infarction (MI), new target lesion revascularization (TLR) and stent thrombosis in follow-up period. METHODS: We included all patients consecutively treated in HCor-ASS with ICP and implantation of at least one drug-eluting stent, between 01/01/2012 to 31/12/2013. Data collection was made of the DESIRE Registry data base in whose program includes these full details of clinical features, and technical information of the intervention, including complications, each of registered patients in addition to the rolling data over defined periods after the index procedure (1, 6 12 months and annually thereafter). It was made the validation of these criteria, using the application SCAI-QIT, which allows definition, when the patient variables are include, the degree of appropriateness implantation of drug-eluting stent. This application is easily accessed via the internet, at the following site: http://scai-qit.org/. After being made the classification of statement of appropriateness criteria, data were statistically analyzed to obtain the objectives and results of the study in question. RESULTS: Among the 1.108 P of DESIRE Registry analyzed using the SCAI-QIT® application, it was observed that: 375 (33,8%) had Appropriate(Group I) indication; 480 (43,3%) had May be appropriate (Group II) indication and 215 (19,4%) had Rarely appropriate (Group II) indication. In Group I, 22,7% had silent ischemia, 13,3% stable angina, 36,8% SCAssST e 27,2% SCAcsST. In Group II, 34,0% had silent ischemia, 11,9% stable angina, 33,3% SCAssST e 20,8% SCAcsST. No Group III, 82,3% had silent ischemia, 4,2% stable angina, 0% SCAssST e 13,5% SCAcsST. The occurrence of MI (defined as increase of CKMB mass >3x the 99 percentile) was 9,6%, 9,6%% and 7,0% (p= 0,652) in Groups I, II e III, respectively. The TLR was 1,9%, 2,1% and 0,9% (p= 0,592) and stent thrombosis rate was 0,3%, 0,6% and 1,4% (p=0,406). Comparing the 3 groups was not statistically significant the rates of mortality and mace in follow-up of 2 years. CONCLUSIONS: The results of this study demonstrate that despite PCI in stable and unstable patients, diverges the expected and already documented, it had no relevance in major events and survival of patients in the clinical follow-up.

Estudos comparativos prévios com inclusão de lesões de bifurcação selecionadas sugerem ausência de benefício de implante eletivo de dois versus stent único. No entanto, a aplicabilidade do técnica provisional parece ser dependente da complexidade da lesão de bifurcação. A área luminar da lesão após tratamento percutâneo, conforme medida pelo ultrassom intracoronário, tem demonstrado valor preditivo significante na evolução tardia dos pacientes submetidos a ICP. Os objetivos desta análise foram avaliar as dimensões luminares de lesões de bifurcação coronária complexas tratadas por ICP, conforme a análise pelo ultrassom, e correlacionar os achados com os resultados imediatos e tardios. Também objetivou-se identificar preditores angiográficos e ultrassonográficos de falência do ramo lateral nos diferentes passos do tratamento e seguimento. Entre maio de 2008 e agosto de 2009, 59 pacientes portadores de lesão de bifurcação complexa, com comprometimento significativo (estenose > 50%) dos dois ramos e lesão no ramo lateral extendendo-se além do óstio, foram abordados inicialmente com pré-dilatação do ramo lateral, a qual foi realizada com sucesso (estenose < 50%, fluxo TIMI 3, sem dissecção) em 54 pacientes (91,5%). Esse pacientes foram então randomizados para tratamento com stent único (estratégia provisional) (n = 27) versus stent duplo (n = 27). Durante o procedimento, 6 pacientes alocados no grupo stent único apresentaram falência do tratamento no ramo lateral (estenose residual >50%, fluxo TIMI < 3 ou dissecção), sendo que, 5 pacientes receberam stent adicional no ramo lateral para otimizar o resultado angiográfico. Ao final do procedimento, os valores médios e desvios padrão (DP) da área mínima do lúmen no óstio do ramo lateral (desfecho primário) foram 3,37 (1,62) mm2 no grupo stent único versus 5,50 (1,41) mm2 no grupo stent duplo (p < 0,001), conforme a alocação randômica. No seguimento angiográfico de 9 meses, as taxas de reestenose no ramo lateral foram 21,7% no grupo stent único versus 4% no grupo stent duplo (p = 0,06), sendo que, todas as recorrências envolveram a localização ostial. Considerando-se o tratamento recebido, a taxa de reestenose no ramo lateral foi significantemente maior nos pacientes tratados com stent único versus stent duplo (27,8% versus 3,3%, p = 0,01). Os preditores de falência da estratégia provisional foram: excêntricidade da lesão (p = 0,02), área mínima do lúmen (p = 0,08) e diâmetro mínimo do lúmen no óstio do ramo lateral (p = 0,06), extensão da lesão (p = 0,09) e percentual de estenose (p = 0,07) do ramo lateral. Com relação a reestenose angiográfica no ramo lateral, os preditores foram: área mínima do lúmen no óstio do ramo lateral ao final do procedimento (p = 0,03), tratamento com stent duplo (p = 0,02), diâmetro mínimo do lúmen (p = 0,03) e percentual de estenose (p = 0,02) no óstio do ramo lateral ao final do procedimento, ganho imediato no óstio do ramo lateral (p = 0,09) e diâmetro de referência do ramo lateral (p = 0,03). Estes resultados sugerem que lesões de bifurcação coronária complexas beneficiam-se de tratamento percutâneo com abordagem inicial com estratégia de dois stents, sendo que, tal benefício esteve relacionado a obtenção de maior área luminar no óstio do ramo lateral. / Previous comparative studies including selected bifurcation lesions have shown no advantage of elective double stenting implantation versus single stenting. However, the applicability of the provisional technique appears to be dependent on the bifurcation lesion complexity. The lesion luminal area after percutaneous treatment, as assessed by intravascular ultrasound, has demonstrated significant predictive value in the late follow-up of patients undergoing PCI. The objectives of this analysis were to evaluate the lesion luminal dimensions of complex coronary bifurcation lesions, as assessed by intravascular ultrasound, and to correlate such findings with acute and late outcomes. Also, it was aimed to identify angiographic and intravascular ultrasound predictors of side branch failure throughout the procedural steps and follow-up. Between may 2008 and august 2009, 59 patients with complex bifurcation lesions, including significant involvement (> 50% stenosis) of both branches and side branch lesion length extending from its ostium, were approached initially with side branch predilatation, which was successful (< 50% stenosis, TIMI 3 flow, no dissection) in 54 patients (91.5%). These patients were then randomized for treatment with single stenting (provisional strategy) (n = 27) versus double stenting (n = 27). During procedure, 6 patients allocated in the single stenting arm presented side branch failure (> 50% residual stenosis, TIMI flow < 3 or dissection), given that 5 patients received an additional stent in the side branch in order to optimize the angiographic result. At final procedure, the mean value and standard deviation (SD) for minimum lumen area at the side branch ostium (primary endpoint) were 3.37 (1.62) mm2 in single stenting versus 5.50 (1.41) mm2 in double stenting (p < 0.001), according to the randomized allocation. In the angiographic follow-up at 9 months, the restenosis rates in the side branch were 21.7% in single stenting versus 4% in double stenting (p = 0.06), given that all recurrences involved the ostial location. Considering the treatment received, the side branch restenosis rate was significantly increase among patients treated with single stenting versus double stenting (27.8% versus 3.3%, p = 0.01). The predictors of provisional strategy failure were: lesion eccentricity (p = 0.02), minimum lumen area (p = 0.08) and minimum lumen diameter in the side branch ostium (p = 0.06), lesion length (p = 0.09) and percent diameter stenosis (p = 0.07) of the side branch. Regarding angiographic restenosis in the side branch, predictors were: minimum lumen area in the side branch ostium at final procedure (p = 0.03), treatment with double stenting (p = 0.02), minimum lumen diameter (p = 0.03) and percent diameter stenosis (p = 0.02) in the side branch ostium at final procedure, acute gain at the side branch ostium (p = 0.09) and side branch reference diameter (p = 0.03). These results suggest that complex coronary bifurcation lesions may benefit from a primary percutaneous approach with double stenting strategy, given that most such benefit was associated with a larger lumen area obtained at the side branch ostium.

Introdução: A gastrostomia percutânea endoscópica (PEG) é utilizada como via de nutrição para pacientes sem capacidade de utilizar a via oral para manter ingestão suficiente. A disfagiaé uma das principais razões para a indicação da PEG, sendo geralmente atribuída a processos neurodegenerativos. Diferentes técnicas e tipos de sonda são utilizadas para confecção da PEG. A técnica de Tração é o método original, na qual a sonda é tracionada a partir de uma pequena incisão na parede abdominal, através a boca e do esôfago até estar posicionada junto da parede gástrica. A técnica de punção com gastropexia é uma variante da técnica de punção original, na qual a sonda não passa pela cavidade oral. Nesta técnica, após fixação do estômago na parede abdominal com uso de pontos, a sonda é introduzida diretamente através da parede abdominal sob visão endoscópica. De acordo com a técnica, diferentes modelos de sondas podem ser utilizadas, cada uma com diferentes tipos de retentores internos. Os retentores internos maiscomuns são: em forma de diamante, em forma de cogumelo, disco rígido e balão. Possivelmente, tanto a técnica de inserção como os modelos de sondas e retentores utilizados podem estar associados a diferentes desfechos. O objetivo deste estudo foi avaliar a incidência podem estar associados a diferentes desfechos. O objetivo deste estudo foi avaliar a incidência. Métodos: Foi realizada uma coorte histórica na qual foram incluídos todos os pacientes maiores de 18 anos submetidos à colocação de uma primeira PEG entre janeiro de 2010 e dezembro de 2015 no Hospital Moinhos de Vento, um hospital privado em Porto Alegre, sul do Brasil. Os dados foram coletados em formulário padronizado através de uma busca no sistema informatizado da Instituição. Para complementação dos dados foi realizada uma busca nos prontuários digitalizados, e em algumas situações realizado contato telefônico. Resultados: Foram identificados 245 pacientes, sendo 200 submetidos a técnica de tração (Pull) e 45 à técnica de punção com gastropexia (Push com gastropexia). A média da idade foi 80,3±13,3 anos. Cento e trinta e quatro (54,7%) pacientes eram do sexo feminino. O período médio de seguimento foi de 17,2±14,6 meses. A indicação mais comum foi doença neurodegenerativa (62,4%), seguido por acidente vascular cerebral (AVC) (16,3%). Todos os pacientes realizaram profilaxia com antibiótico no dia do procedimento. A mediana de dias de internação pós PEG foi de 8 dias. O modelo de sonda mais utilizado foi o retentor em forma de diamante (51,8/%). A colocação da PEG foi bem-sucedida em 99,6% dos casos. A mortalidade geral foi de 42,4% (104/245) durante o período de seguimento. Nenhum óbito foi atribuído diretamente a complicações relacionadas ao procedimento. Entretanto, três pacientes faleceram dentro de 48 horas após o procedimento: um por sepse respiratória, outro por parada cardiorrespiratória e o terceiro que realizou a PEG ambulatorial teve morte súbita no domicílio. A taxa de complicações (maiores ou menores) foi de 23,6%, sendo a mais frequente, a retirada acidental da sonda, que ocorreu em 17,1% dos pacientes em algum momento do seu seguimento. Não foi observada diferença entre as técnicas de realização da PEG gastrostomia com a incidência desta complicação. O tempo até a retirada acidental da sonda foi menor entre os pacientes cujas sondas tinham o retentor interno em forma de diamante em relação aos demais retentores (p = 0,02). Sepultamento do retentor interno (Buried Bumper Syndrome) ocorreu em 5,4% dos casos, todos submetidos a técnica de tração (p = 0,08). Pacientes portadores de sonda com retentor em forma de diamante apresentaram maior incidência de complicações gerais (p = 0,02) e de retirada acidental (p = 0,01), comparativamente aos pacientes portadores de sondas com outros tipos de retentor. Conclusões: A PEG é uma técnica segura, com baixa taxa de mortalidade diretamente associada ao procedimento. Entretanto, devido a população na qual o procedimento é realizado, a mortalidade geral é elevada. Complicações menores são frequentes, independentemente da técnica ou tipo de sonda utilizada, porém a técnica e o tipo de sonda parecem associadas a um perfil diferente de complicações. Perspectivas: O desenvolvimento da técnica, o desenvolvimento de materiais com melhor perfil de segurança e, especialmente, o aprimoramento das orientações e cuidados pós-gastrostomia são necessários para reduzir a incidência de complicações em pacientes submetidos a esse tipo de procedimento. Novos estudos comparando de maneira prospectiva e randomizada diferentes técnicas e modelos de sonda são necessários para determinar se há uma técnica ou modelo a ser utilizado como primeira escolha.

Le stratum corneum (SC), couche supérieure de l’épiderme, est composé principalement de cornéocytes entourés d’une matrice lipidique. Cette structure particulière confère au SC son rôle de barrière et protège l’organisme de la perte en eau, de la pénétration de substances exogènes et de l’irradiation ultra-violette (UV). La matrice lipidique du SC est constituée de trois lipides majeurs : les céramides, les acides gras et le cholestérol organisés en phase cristalline. Cette matrice est la principale voie de pénétration des molécules exogènes à travers la peau. L’estimation de l’absorption cutanée pour l’analyse du risque des produits cosmétiques est basée sur les recommandations de l’Organisation de Coopération et de Développement Économiques (OCDE) qui prend en compte les propriétés physicochimiques des molécules i.e. Log Pow (lipophilie) et MW (masse moléculaire). En effet, l’OCDE considère une absorption de 100% pour une molécule ayant une MW inférieure à 500g/mol et un Log Pow compris en -1 et +4. En dehors de ces valeurs, l’OCDE applique une estimation de 10%. Hors, cette estimation est bien souvent loin de la réalité et a besoin d’être affinée. Notre travail s’est focalisé sur le développement d’un critère d’évaluation de la pénétration cutanée afin de moduler les données de l’OCDE par trois approches différentes : chromatographie d’affinité, spectroscopie de fluorescence et microspectroscopie infra-rouge à transformée de Fourier (FTIR) avec une source synchrotron. Etant donné que les propriétés barrières de la peau sont étroitement liées à la composition en céramides du SC, les méthodes développées en chromatographie d’affinité et spectroscopie de fluorescence se sont focalisées sur l’interaction céramide-molécules. Un critère prédictif de la pénétration percutanée a été défini avec chacune de ces méthodes :  et I. La troisième méthodologie a consisté à développer un autre critère (Sindex) par microspectroscopie FTIR avec une source synchrotron. La distribution cutanée des molécules a été suivie sur coupes microtomées de biopsies humaines. A partir de Sindex, une cartographie prédictive de la pénétration percutanée des molécules a été établie. Notre design expérimental comprenait des molécules (filtres UV, conservateurs, actifs cosmétiques) avec des Log Pow et MW variés (cf annexe 1). La pénétration cutanée de ces molécules a été étudiée avec une méthode de référence : cellules de Franz couplées à la chromatographie. Ces données de référence ont servi à valider les modèles et critères prédictifs développés. Ce travail a permis d’explorer de nouvelles pistes pour l’étude prédictive de la pénétration percutanée et de développer ainsi de nouveaux critères. Utilisés en complément des propriétés physicochimiques des molécules, ces nouveaux critères permettent d’affiner l’estimation de la pénétration cutanée de molécules exogènes pour l’analyse du risque. / The stratum corneum (SC) is the upper skin layer and due to its particular composition, corneocytes embedded in a lipidic matrix, it owns a role of barrier function and protects our body against water loss, penetration of exogenous molecules and UV irradiation. Its lipidic matrix is composed of three major lipids: fatty acids, cholesterol and ceramides, organised in liquid crystalline phase. This high cohesion creates cement between corneocytes. This cement is the principal pathway taken by the exogenous molecules to penetrate the skin. Percutaneous penetration estimation of cosmetic products is today based on the Organisation for Economic Co-operation and Development (OECD) recommendations, regarding molecules structural characteristics i.e. Log Pow (polarity) and MW (molecular weight). The OECD claims that 100% dermal absorption may be assumed if the exogenous molecule molecular mass is lower than 500 g/mol and Log Pow ranged between -1 and +4. Besides these values, a 10% coefficient is applied. This approach is sometimes far from reality. Our work focused on developing new evaluation criteria of percutaneous penetration from three different approaches: affinity chromatography, fluorescence spectroscopy and FTIR microspectroscopy with a synchrotron source in order to modulate OECD predictions. Considering that skin barrier properties are closely linked to ceramide composition and conformation within the SC, two methods were developed to study the interaction between ceramides and exogenous molecules by affinity chromatography and fluorescence spectroscopy. A predictive criterion of percutaneous penetration was developed from each of these methods:  and I. The third methodology consisted of developing a predictive criterion, Sindex, by FTIR microspectroscopy with a synchrotron source, on microtomized cuts of human skin biopsies. A predictive cartography was build from Sindex. Our experimental design included exogenous molecules (e.g. UV filters, preservatives, cosmetic actives) with various Log Pow and MW (cf annexe 1). Molecules skin penetration was studied with a Franz cell device coupled to HPLC analysis. These results served as reference data to validate our predictive models and criteria.This work permitted to set up new methods for predicting skin penetration of exogenous molecules and to develop complementary predictive criterion to Log Pow and MW. These new criterion will serve to modulate OECD predictions.