Made available in DSpace on 2015-07-22T20:50:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-25 / Stanich P. Relevância dos aspectos nutricionais na sobrevida de pacientes com Doença do Neurônio Motor. São Paulo; 2001. [Tese de Doutorado- Escola Paulista de Medicina – Universidade Federal de São Paulo]. Objetivos. Avaliar o efeito dos aspectos nutricionais na sobrevida de pacientes com Doença do Neurônio Motor (DNM) e apresentar as variáveis preditivas para a indicação de terapia nutricional enteral, por gastrostomia endoscópica percutânea (GEP). Material e Métodos. Foi um estudo longitudinal tipo coorte retrospectiva, de 2000 a 2008, e a casuística constituída por 128 pacientes com DNM. Variáveis clínicas, nutricionais e respiratórias foram analisadas. As análises foram conduzidas adotando-se a sobrevida como variável dependente. A sobrevida foi avaliada pela Curva de Kaplain - Meier. As variáveis que apresentaram nível de significância de 20% (p< 0,20) foram selecionadas para o modelo de regressão proporcional de Cox. Resultados. Cento e onze pacientes realizaram a gastrostomia, sendo 59 com a forma apendicular (ELA) e 52 com a forma bulbar (PBP). A desnutrição estava presente em 32% da população antes da GEP, com maior frequência nos pacientes com ELA. O tempo de sobrevida após a GEP foi de 11 meses para os pacientes com PBP e 16 meses para ELA (p< 0,05). As variáveis associadas à sobrevida foram: precocidade na indicação da GEP; redução de CVF %, idade e IMC antes da GEP (hazard ratio de 0, 254 e p = 0, 007) para os pacientes com ELA e exclusão da alimentação por via oral e traqueostomia (hazard ratio de 0, 345 e p= 0, 014) para os pacientes com PBP. Ao final do modelo as variáveis mais associadas com a sobrevida foram precocidade na indicação de GEP, exclusão da alimentação por via oral, para os pacientes com PBP e estado nutricional antes da GEP para os pacientes com ELA. Conclusões. A inserção precoce de gastrostomia endoscópica percutânea, a partir do momento diagnóstico, foi fator protetor para a sobrevida dos pacientes. A desnutrição foi fator prognóstico ruim, especialmente para os pacientes com ELA. Vigilância nutricional durante a evolução da doença pode melhorar os resultados quando o objetivo é aumentar a sobrevida de pacientes com DNM/ELA. / Aims. To evaluate the effect of nutrition on survival of patients with Motor Neurone Disease (MND) and present the predictor variables for indications of nutritional therapy, percutaneous endoscopic gastrostomy (PEG). Methods. It was a retrospective longitudinal cohort study, from 2000 to 2008, and the sample consisted of 128 patients with MND. The variables investigated were clinical, nutritional and respiratory were analysed. Analyses were conducted by adopting the survival as the dependent variable. The survival curve was evaluated by Kaplain - Meier. The variables that had a significance level of 20% (p <0.20) were selected for the proportional regression model of Cox. Results. One hundred and eleven patients underwent gastrostomy, and 59 limb onset (ALS) and 52 with bulbar onset (PBP). Malnutrition was present in 32% of the population before PEG, most frequently in patients with limb onset. The survival time after PEG was 10.5 months for patients with PBP and 16 months for ALS (p <0.05). Variables associated with survival were: early indication in the PEG, for ALS and PBP; reduction of FVC% and BMI before PEG (hazard ratio of 0, 254, p = 0, 007) for patients with limb onset and exclusion of oral feeding and tracheostomy (hazard ratio of 0, 345, p = 0, 014) for patients with bulbar onset. Conclusions. Early insertion of percutaneous endoscopic gastrostomy, from the time diagnosis was a protective factor for patient survival. Malnutrition was a bad prognostic factor, especially for patients with limb onset. Nutritional surveillance for disease progression may improve results when the goal is to increase the survival of patients with MND / ALS. / TEDE / BV UNIFESP: Teses e dissertações

Abstract In the Czech Republic there is no doubt about the tendency of gradual increase in median life expectancy, which is significantly affected by the fact that mortality from cardiovascular diseases, especially from acute coronary syndromes, has been decreasing. Besides the provable effect of a healthy lifestyle, diet and, by all means, a quality and effective pharmacotherapy, a significant development in the field of interventional cardiology contributes to this accomplishment. The number of coronographies, coronary angioplasties and implanted stents have multiplied, and today the invasive coronarographic diagnostics and percutaneous myocardial revascularization belong to the the most common diagnostic and therapeutic methods in treatment of acute forms of ischemic heart diseases. An obvious prerequisite for such a rapid development in the field of intervention coronary angiography was the establishment of a sufficiently dense network of catheter laboratories and specialized facilities, which provide a highly professional and intensive care for patients. This thesis is focused on three basic objectives: ? To survey and characterize differences in nursing care concerning various complications in patients after SKG / PCI ? To survey bio / psycho / social impacts of complications after SKG / PCI on a patient ? To identify and summarize personal and material prerequisites and requirements to ensure quality nursing care for these complicated conditions The research was conducted by using a qualitative methodology. The methods used were observation, non-standardized interviews and medical and nursing records analyses. The research survey samples on which the investigation was focused were patients with the acute coronary syndrome hospitalized in the coronary care unit in the Cardio Center in České Budějovice, their family members and also the nursing staff providing the comprehensive nursing care. The outcomes of this survey were eleven descriptive case reports characterizing the occurrence of the most frequent complications in patients with ACS after SKG / PCI. To ensure clarity, each case study is complemented by a thought map with an account of the most important nursing interventions in the management of specific acute conditions. The paper also contains a framework analysis of bio / psycho / social impacts of complicated situations on patients. It is interesting to compare this matter from the perspective of nurses and patients, which is seen in correlation graphs. The section describing the organizational and personnel provision is introduced with the characteristics of the medical process and it also contains the list of medical personnel with their qualifications and the length of experience in the Coronary care unit in České Budějovice. Summarization of the instrumental medical equipment is also based on the analysis of previous cases and is accompanied by photographs of the equipment typical and indispensable for the care of patients in the Coronary care unit, which primarily has an informative and complementary character to get an integrated view of the Coronary care unit running and the nursing staff work.

INTRODUÇÃO: Poucas são as estratégias testadas para reduzir o volume de contraste durante angioplastia coronária. Levantamos a hipótese de que o ultrassom intravascular teria o potencial de substituir muitas informações fornecidas pela angiografia, reduzindo, dessa forma, o volume total de contraste utilizado durante a angioplastia coronária. MÉTODOS: No total, 83 pacientes foram randomizados para realização de angioplastia guiada pela angiografia isolada ou angioplastia guiada pelo ultrassom intravascular. Ambos os grupos foram tratados com estratégias rigorosas para redução de contraste, tendo como objetivo primário o volume final de contraste utilizado na angioplastia coronária. Os pacientes foram acompanhados por um período médio de 4 meses. RESULTADOS: A mediana do volume total de contraste foi de 64,5 ml (intervalo interquartil [ITQ], 42,8-97 ml; mínimo de 19 ml e máximo de 170 ml) no grupo angioplastia guiada pela angiografia isolada vs. 20 ml (ITQ, 12,5-30 ml; mínimo de 3 ml e máximo de 54 ml) no grupo angioplastia guiada pelo ultrassom intravascular (P < 0,001). De forma semelhante, a mediana da razão entre o volume de contraste e o clearance de creatinina foi significantemente menor entre os pacientes submetidos a angioplastia guiada pelo ultrassom intravascular, quando comparados aos pacientes do grupo angioplastia guiada pela angiografia isolada (1 [ITQ, 0,6-1,9] vs. 0,4 [ITQ, 0,2- 0,5], respectivamente; P < 0,001). Os desfechos intra-hospitalares e aos 4 meses de acompanhamento não foram diferentes entre os pacientes randomizados para o grupo angioplastia guiada pela angiografia isolada e aqueles do grupo angioplastia guiada pelo ultrassom intravascular. CONCLUSÕES: A utilização racional do ultrassom intravascular como método de imagem para guiar a angioplastia foi segura e reduziu de forma significativa o volume de contraste, comparativamente à angioplastia guiada pela angiografia isolada. O uso do ultrassom intravascular para esse propósito deve ser considerado para pacientes de elevado risco para o desenvolvimento de nefropatia induzida pelo contraste ou sobrecarga de volume e que serão submetidos a angioplastia coronária / BACKGROUND: To date, few approaches have been described to reduce the final dose of contrast agent in percutaneous coronary intervention. We hypothesized that intravascular ultrasound might serve as an alternative imaging tool to angiography in many steps during percutaneous coronary intervention, thereby reducing the use of iodine contrast. METHODS: A total of 83 patients were randomized to angiography alone-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. Both groups were treated according to a pre-defined meticulous procedural strategy, and the primary endpoint was the total volume contrast agent used during percutaneous coronary intervention. Patients were followed clinically for an average of 4 months. RESULTS: The median total volume of contrast was 64.5 mL (interquartile range [IQR], 42.8 to 97 mL; minimum, 19 mL; maximum, 170 mL) in the angiography alone-guided group vs. 20 mL (IQR, 12.5 to 30 mL; minimum, 3 mL; maximum, 54 mL) in the intravascular ultrasound-guided group (P < 0.001). Similarly, the median volume of contrast/creatinine clearance ratio was significantly lower among patients treated with intravascular ultrasound-guided percutaneous coronary intervention when compared with patients treated with angiography alone-guided percutaneous coronary intervention (1 [IQR, 0.6 to 1.9] vs. 0.4 [IQR, 0.2 to 0.6], respectively; P < 0.001). In-hospital and 4-month outcomes were not different between patients randomized to angiography alone-guided and intravascular ultrasound-guided percutaneous coronary intervention. CONCLUSIONS: Thoughtful and extensive use of intravascular ultrasound as the primary imaging tool to guide percutaneous coronary intervention was safe and markedly reduced the volume of iodine contrast compared with angiographyalone guidance. The use of intravascular ultrasound should be considered for patients at high risk of contrast-induced acute kidney injury or volume overload undergoing coronary angioplasty

Introdução: A liberação de biomarcadores de necrose miocárdica após a intervenção coronária percutânea (ICP) ocorre frequentemente. No entanto, a correlação entre a liberação dos biomarcadores e o diagnóstico do infarto agudo do miocárdio (IAM) tipo 4a tem gerado controvérsia, especialmente com o aumento da sensibilidade nos ensaios de troponina (Tn). Neste estudo, objetivamos quantificar a liberação dos biomarcadores cardíacos em pacientes submetidos à ICP eletiva sem o surgimento de novo realce tardio pelo gadolínio (RTG) na ressonância magnética cardíaca (RMC) após o procedimento. Métodos: Foram incluídos pacientes consecutivos com doença arterial coronária estável e função ventricular preservada, com indicação eletiva para ICP em pelo menos duas artérias epicárdicas. RMC com RTG foi realizada em todos os pacientes antes e depois das intervenções. Medidas seriadas de Tn e creatinoquinase fração MB (CK-MB) foram realizadas imediatamente antes do procedimento até 48 horas após. Pacientes com novo RTG na RMC após o procedimento foram excluídos. Resultados: 71 pacientes foram referenciados para a realização eletiva da ICP sendo que 15 (21,1%) foram excluídos, 10 (14,1%) por causa do surgimento de um novo RTG na RMC após a ICP. Nos 56 pacientes sem a evidência de IAM tipo 4a pela RMC predominava o gênero masculino 37 (66,1%) com idade média de 61,7 (± 8,4) anos e escore de SYNTAX médio de 16,6 (± 7,7). Após a ICP, 48 (85,1%) pacientes apresentaram um pico de elevação de Tn acima do percentil 99 sendo que em 32 (57,1%) a elevação foi superior a 5 vezes esse limite, enquanto que apenas 2 (3,6%) apresentaram um pico de CK-MB maior do que 5 vezes o percentil 99. A mediana do pico de liberação da Tn foi de 0,290 (0,061 - 1,09) ng/mL, valor 7,25 vezes superior ao percentil 99. Conclusão: Diferentemente da CK-MB, a liberação da troponina I ocorre com frequência após procedimento de ICP mesmo na ausência de realce tardio pelo gadolínio na ressonância magnética cardíaca / Background: The release of myocardial necrosis biomarkers after percutaneous coronary intervention (PCI) frequently occurs. However, the correlation between biomarker release and the diagnosis of procedurerelated myocardial infarction (MI) (type 4a) has been controversial. This study aims to evaluate the amount and pattern of cardiac biomarker release after elective PCI in patients without the image of a new MI after the procedure assessed by cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE). Methods: Patients with normal baseline cardiac biomarkers referred for elective PCI were prospectively included. CMR with LGE was performed in all of the patients before and after the interventions. Measurements of troponin I (TnI) and creatinekinase MB fraction (CK-MB) were systematically performed before and after the procedure. Patients with a new LGE on the post-procedure CMR were excluded. Results: Of the 56 patients without the evidence of a procedure-related MI assessed by the CMR after PCI, 48 (85.1%) exhibited a TnI elevation peak above the 99th percentile. In 32 (57.1%), the peak was greater than 5 times this limit. On the other hand, 17 (30.4%) had a CK-MB peak above the limit of the 99th percentile, and this peak was greater than 5 times the 99th percentile in only 2 patients (3.6%). The median peak release of TnI was 0.290 (0.061 to 1.09) ng/ml, which is 7.25-fold higher than the 99th percentile. Conclusions: In contrast to CK-MB, TnI release often occurs after an elective PCI procedure, despite the absence of a new LGE on CMR

Les neurotoxiques organophosphorés sont appelés agents chimiques de guerre car ils sont une menace à la fois pour les militaires et pour les populations civiles. La voie percutanée est l’une des principales voies d’entrée pour ces agents, et plus particulièrement pour le VX, très peu volatil. La décontamination des surfaces exposées est alors cruciale afin d’éviter l’intoxication des victimes. En cas d’attentat terroriste, le cuir chevelu humain pourrait être un site préférentiel d’exposition. Cette partie du corps, riche en follicules pileux, pourrait nécessiter des produits et des processus de décontamination adaptés. Ce travail est divisé en 4 parties : 1) Validation d’un modèle de peau in vitro pour le cuir chevelu humain ; 2) Détermination des stratégies de décontamination ; 3) Formulation de nouveaux systèmes de décontamination ; 4) Évaluation de leur efficacité de décontamination. La peau d’oreille de porc est un modèle pertinent pour l’étude de la pénétration percutanée in vitro du VX à travers le cuir chevelu humain. La peau de dessus de tête de porc représente un bon modèle de cuir chevelu humain pour l’étude de l’affinité du VX avec la tige pilaire. L’étude de distribution du VX selon différents temps d’exposition a montré que la majorité du toxique reste à la surface de la peau jusqu’à 2h d’exposition. Il est donc intéressant de décontaminer la peau même après 2h d’exposition aux agents chimiques de guerre. Les microémulsions comprenant un actif détoxifiant (oxime) sont les systèmes les plus efficaces car ils pénètrent en profondeur afin de venir détruire le toxique in situ dans la peau. Les poudres et les émulsions de Pickering ont une action de surface et permettent d’extraire le toxique présent à la surface de la peau et dans les couches superficielles. Les résultats de nos études in vitro ont montré que ces formulations sont significativement plus efficaces que la terre à foulon pour une décontamination après 45 min d’exposition au VX / Organophosphorous nerve agents are designed as chemical warfare agent because they represent a threat both for the military and the civilians. Due to its low volatility, VX mainly remains in its liquid form and mostly presents a contamination by skin contact. Decontamination of exposed body surface is therefore crucial to prevent victims' poisoning. In case of terrorist acts, civilian human scalp could be a preferential site of exposure. This body region, rich in hair follicles, may require adapted decontamination products and procedures. The aims of this work are: 1) Validation of a relevant in vitro human scalp skin model; 2) Determination of decontamination strategies; 3) Formulation of new decontamination systems; 4) Evaluation of their decontamination efficacy. Pig ear skin is a relevant model when studying the in vitro percutaneous penetration of VX through human scalp. Pig skull roof skin could be used when studying the affinity of VX for hair. This study has shown that most of the nerve agent remains on the skin surface up to 2h of exposure, which means that it is worth decontaminating even if contamination occurred 2h before. Microemulsions loading a detoxifying agent (oxime) are the most efficient systems because they are able to penetrate deeper into the skin to neutralize the agent in situ. Adsorbing powders and Pickering emulsions could interact with the agent present on the skin surface and in the superficial layers. Our results from the in vitro experiments have demonstrated that these formulations are more efficient than Fuller's earth for skin decontamination after 45 min of VX exposure

Estudo comparativo entre os custos dos tratamentos clínico, cirúrgico ou percutâneo em portadores de doença multiarterial coronária estável - 5 anos de seguimento [tese]. São Paulo: Faculdade de Medicina, Universidade de São Paulo, 2013. INTRODUÇÃO: As principais opções terapêuticas para a doença multiarterial coronária incluem cirurgia de revascularização miocárdica (CRM), intervenção coronária percutânea (ICP) e tratamento clínico (TC). Essas três estratégias terapêuticas apresentam eficácia similar em determinados subgrupos de pacientes. No presente momento, estudos direcionados à análise econômica são escassos, e contemplam, principalmente, os custos comparativos entre as intervenções cirúrgica e percutânea. OBJETIVOS: Analisar, prospectivamente, o custo comparativo das três formas terapêuticas da doença multiarterial coronária estável, durante cinco anos de seguimento. MÉTODOS: Foi computado o custo terapêutico global de 611 pacientes do ensaio clínico The Second Medicine, Angioplasty, or Surgery Study (MASS II), baseado na remuneração provida pelo sistema de saúde suplementar do Instituto do Coração do HC/FMUSP, tomando-se os valores em moeda nacional corrente. Realizou-se, posteriormente, análise de custo-efetividade para o tempo livre de eventos clínicos e o tempo livre de eventos acrescido de tempo livre de angina. RESULTADOS: O TC apresentou 3.79 e 2.07 QALY (quality-adjusted lifeyears); o ICP apresentou 3.59 e 2.77 QALY; e o CRM apresentou 4.4 e 2.81 QALY, respectivamente, para sobrevida livre de eventos e sobrevida livre de eventos e angina. Os custos para sobrevida livre de eventos foram R$ 16.327,80 para TC, R$ 35.940,60 para ICP e R$ 32.873,40 para CRM. A análise pareada dos custos para sobrevida livre de eventos mostrou que houve diferença significante favorecendo TC contra ICP (P < 0,01), e em comparação com CRM (P < 0,01); e CRM versus ICP (P = 0,01). Os custos para sobrevida livre de eventos e angina foram R$ 29.795,40, R$ 46.495,80 e R$ 44.305,20, respectivamente. A comparação pareada dos custos livres de eventos mais livres de angina demonstrou que houve diferença significante favorecendo TC contra ICP (P = 0,04), e em comparação com CRM (P < 0,001). Não houve diferença entre CRM e ICP (P > 0,05). CONCLUSÃO: A análise comparativa entre as diferentes opções terapêuticas desta amostra revelou que TC foi mais custo-efetivo que CRM, e esta, por sua vez, mais custo-efetivo que ICP / BACKGROUND: The therapeutic options for multivessel coronary artery disease are coronary artery bypass graft surgery (CABG), percutaneous coronary intervention (PCI), or medical treatment alone (MT). These three therapeutic strategies present similar efficacy for specific subgroups. At the present moment, economic outcome trials are scant, and contemplate comparative cost between surgical or percutaneous intervention. OBJECTIVE: To analyze, prospectively, the comparative cost from three therapeutic strategies in multivessel coronary artery disease, at 5-year of follow-up. METHODS: We analyzed cumulative costs of 611 patients from clinical trial The Second Medicine, Angioplasty, or Surgery Study (MASS II). The economic analysis is based on remuneration provided by the supplementary health system of the Heart Institute of the Clinical Hospital of FMUSP, expressing these values in Brazilian currency. It was compared to the cumulative costs of each therapeutic strategy in the 5-year follow-up period. A cost-effectiveness analysis was then conducted for event-free survival and event plus angina-free survival. Cost-effectiveness analysis was performed by quality-adjusted life- year (QALY) analysis. RESULTS: Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years (QALY) and 2.07 QALY; PCI presented 3.59 and 2.77 QALY; and CABG demonstrated 4.4 and 2.81 QALY. The event-free costs were R$ 16327.80 for MT; R$ 35940.60 for PCI; and R$ 32873.40 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P < 0.01) and versus CABG (P < 0.01) and CABG versus PCI (P =0.01). The event-free plus angina-free costs were R$ 29795.40, R$ 46495.80 e R$ 44305.20, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P =0.04), and versus CABG (P < 0.001); there was no difference between CABG and PCI (P > 0.05). CONCLUSION: The comparative analysis among the different therapeutic strategies demonstrated that MT was more cost-effective than CABG, and this than PCI

Ziel der Studie war es zu analysieren, welchen Einfluss eine angiographisch sichtbare Kollateralisierung vor Revaskularisation bei Patienten mit einem akuten ST-Elevations-Myokardinfarkt (STEMI) und primärer perkutaner Koronarintervention (PCI) auf verschiedene in der kardialen Magnetresonanztomographie messbare Parameter und auf die klinische Prognose hat. Es wurden 235 Patienten mit STEMI und einem Symptombeginn <12 Stunden in die Analyse eingeschlossen. Alle Patienten wiesen einen funktionell insuffizienten antegraden Fluss in der Infarktarterie auf. Die Patienten wurden in zwei Gruppen unterteilt: Gruppe A mit fehlender oder nur geringer Kollateralversorgung (n=166) und Gruppe B mit einer signifikanten Kollateralisierung (n=69). Es wurden Infarktgröße, mikrovaskuläre Obstruktion und linksventrikuläre Funktion mittels Magnetresonanztomographie im Median 3 Tage nach dem Infarktereignis bestimmt sowie die Patienten über einen Zeitraum von >2 Jahren nachbeobachtet. Das Ausmaß der frühen mikrovaskulären Obstruktion war in Gruppe B signifikant geringer (3,3% gegenüber 2,1% der linksventrikuläre Masse, p = 0,009). Die mittels maximaler Kreatinkinase-MB-Ausschüttung gemessene Infarktgröße war in Gruppe B kleiner (p=0,02). Bei 227 Patienten (97%) wurde nach im Median 2,2 Jahren eine klinische Verlaufskontrolle durchgeführt. Insgesamt starben während des Kontrollzeitraums 25 Patienten: 22 Patienten (13,8%) der Gruppe A mit fehlender oder nur schwacher Kollateralisierung und 3 Patienten (4,4%) der Gruppe B mit signifikanter Kollateralversorgung vor Behandlungsbeginn (p=0,04). In Gruppe A traten 12 (7,5%) nicht-tödliche Reinfarkte auf im Vergleich zu 2 (2,9%) in Gruppe B (p=0,18). Ein kombinierter Endpunkt aus Tod oder nicht-tödlichem Reinfarkt trat in Gruppe B signifikant seltener auf als in Gruppe A (p=0,02). Zusammenfassend lässt sich formulieren, dass gut ausgebildete Kollateralgefäße vor einer Revaskularisation mittels PCI bei Patienten mit akuten STEMI mit einer schützenden Wirkung auf die koronare Mikrozirkulation und einem besseren Langzeit-Überleben assoziiert sind.:1 BIBLIOGRAPHISCHE BESCHREIBUNG 2 ABKÜRZUNGSVERZEICHNIS 3 EINFÜHRUNG 4 AUFGABENSTELLUNG 5 MATERIALIEN UND METHODEN 5.1 Überblick über das Studiendesign 5.2 Koronarintervention 5.3 Enzymatische Infarktgröße 5.4 Kardiale Magnetresonanztomographie 5.4.1 Linksventrikuläre Volumina und Ejektionsfraktion 5.4.2 Infarktgröße 5.4.3 Mikrovaskuläre Obstruktion 5.5 Klinisches Follow-up 5.6 Statistik 6 ERGEBNISSE 6.1 Patientencharakteristika 6.2 Enzymatische Infarktgröße 6.3 Magnetresonanztomographie 6.4 Klinische Ereignisse im Langzeitverlauf 6.5 Prädiktoren klinischer Ereignisse 6.5.1 Univariate Cox-Regressions-Analyse 6.5.2 Multivariate Cox-Regressions-Analyse 6.6 Klinische Ergebnisse in Abhängigkeit von der Zeit zwischen Symptombeginn und Reperfusion 6.7 Magnetresonanztomographische Ergebnisse in Abhängigkeit von der Zeit zwischen Symptombeginn und Reperfusion 7 DISKUSSION 7.1 Limitationen 8 ZUSAMMENFASSUNG DER ARBEIT 9 LITERATURVERZEICHNIS 10 DANKSAGUNG 11 ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT 12 LEBENSLAUF 13 PUBLIKATIONEN

Ziel der Studie war es zu analysieren, welchen Einfluss eine angiographisch sichtbare Kollateralisierung vor Revaskularisation bei Patienten mit einem akuten ST-Elevations-Myokardinfarkt (STEMI) und primärer perkutaner Koronarintervention (PCI) auf verschiedene in der kardialen Magnetresonanztomographie messbare Parameter und auf die klinische Prognose hat. Es wurden 235 Patienten mit STEMI und einem Symptombeginn <12 Stunden in die Analyse eingeschlossen. Alle Patienten wiesen einen funktionell insuffizienten antegraden Fluss in der Infarktarterie auf. Die Patienten wurden in zwei Gruppen unterteilt: Gruppe A mit fehlender oder nur geringer Kollateralversorgung (n=166) und Gruppe B mit einer signifikanten Kollateralisierung (n=69). Es wurden Infarktgröße, mikrovaskuläre Obstruktion und linksventrikuläre Funktion mittels Magnetresonanztomographie im Median 3 Tage nach dem Infarktereignis bestimmt sowie die Patienten über einen Zeitraum von >2 Jahren nachbeobachtet. Das Ausmaß der frühen mikrovaskulären Obstruktion war in Gruppe B signifikant geringer (3,3% gegenüber 2,1% der linksventrikuläre Masse, p = 0,009). Die mittels maximaler Kreatinkinase-MB-Ausschüttung gemessene Infarktgröße war in Gruppe B kleiner (p=0,02). Bei 227 Patienten (97%) wurde nach im Median 2,2 Jahren eine klinische Verlaufskontrolle durchgeführt. Insgesamt starben während des Kontrollzeitraums 25 Patienten: 22 Patienten (13,8%) der Gruppe A mit fehlender oder nur schwacher Kollateralisierung und 3 Patienten (4,4%) der Gruppe B mit signifikanter Kollateralversorgung vor Behandlungsbeginn (p=0,04). In Gruppe A traten 12 (7,5%) nicht-tödliche Reinfarkte auf im Vergleich zu 2 (2,9%) in Gruppe B (p=0,18). Ein kombinierter Endpunkt aus Tod oder nicht-tödlichem Reinfarkt trat in Gruppe B signifikant seltener auf als in Gruppe A (p=0,02). Zusammenfassend lässt sich formulieren, dass gut ausgebildete Kollateralgefäße vor einer Revaskularisation mittels PCI bei Patienten mit akuten STEMI mit einer schützenden Wirkung auf die koronare Mikrozirkulation und einem besseren Langzeit-Überleben assoziiert sind.:1 BIBLIOGRAPHISCHE BESCHREIBUNG 2 ABKÜRZUNGSVERZEICHNIS 3 EINFÜHRUNG 4 AUFGABENSTELLUNG 5 MATERIALIEN UND METHODEN 5.1 Überblick über das Studiendesign 5.2 Koronarintervention 5.3 Enzymatische Infarktgröße 5.4 Kardiale Magnetresonanztomographie 5.4.1 Linksventrikuläre Volumina und Ejektionsfraktion 5.4.2 Infarktgröße 5.4.3 Mikrovaskuläre Obstruktion 5.5 Klinisches Follow-up 5.6 Statistik 6 ERGEBNISSE 6.1 Patientencharakteristika 6.2 Enzymatische Infarktgröße 6.3 Magnetresonanztomographie 6.4 Klinische Ereignisse im Langzeitverlauf 6.5 Prädiktoren klinischer Ereignisse 6.5.1 Univariate Cox-Regressions-Analyse 6.5.2 Multivariate Cox-Regressions-Analyse 6.6 Klinische Ergebnisse in Abhängigkeit von der Zeit zwischen Symptombeginn und Reperfusion 6.7 Magnetresonanztomographische Ergebnisse in Abhängigkeit von der Zeit zwischen Symptombeginn und Reperfusion 7 DISKUSSION 7.1 Limitationen 8 ZUSAMMENFASSUNG DER ARBEIT 9 LITERATURVERZEICHNIS 10 DANKSAGUNG 11 ERKLÄRUNG ÜBER DIE EIGENSTÄNDIGE ABFASSUNG DER ARBEIT 12 LEBENSLAUF 13 PUBLIKATIONEN

Le choc cardiogénique (CC) est un état d’hypoperfusion critique des organes cibles causé par une dysfonction profonde du myocarde. Cette situation dangereuse et dynamique nécessite des interventions rapides de la part d'une équipe multidisciplinaire pour sauver la vie du patient, mais le risque de décès demeure encore très élevé́. Actuellement, l’utilité des dispositifs d’assistance ventriculaire percutanés (DAVp) pour traiter le CC n’est pas suffisamment étudiée. Concevoir un modèle artificiel de CC pourrait faciliter la compréhension du CC ainsi que le développement de nouveaux DAVp. Au cours de ce projet, nous nous sommes premièrement intéressés au sujet en synthétisant les données cliniques sur l’utilisation des DAVp dans un contexte de CC compliquant un infarctus du myocarde (IM-CC) sous forme de revues systématiques. Par la suite, nous avons conçu un projet expérimental visant à démontrer la faisabilité d’un modèle animal stable d’IM-CC en induisant par méthode percutanée un infarctus étendu de la paroi antérieure in vivo chez le porc qui pourrait être utilisé pour fournir des données physiologiques supportant la création d’un modèle artificiel d’haute-fidélité. L’état de CC stable a été confirmé par une combinaison de données hémodynamiques et de laboratoire et l’ampleur de l’infarctus a été validée par des techniques de coloration ex vivo. Ayant atteint notre objectif primaire de ≥50% de survie suite à l’infarctus et l’induction d’un état de CC chez 50% des cochons, nous concluons que notre modèle animal est suffisamment stable pour procéder à la prochaine étape de notre programme. / Cardiogenic shock (CS) is a state of critical end-organ hypoperfusion resulting from profound myocardial dysfunction that is both dangerous and dynamic and requires rapid, coordinated multidisciplinary care in order to prevent mortality. However, despite appropriate medical management, the risk of early mortality remains high. Percutaneous mechanical support devices (pMCS) offer the promise of correcting pump dysfunction, but their clinical utility in CS remains debated and understudied. Developing a reliable synthetic model of CC could both improve our understanding of CS and accelerate the development of the next generation of pMCS devices. In this work, we first present the results of two systematic reviews of the comparative effectiveness of currently available pMCS devices in the setting of post-acute myocardial infarction CS (AMI-CS). We then sought to demonstrate the feasibility of creating a stable animal model of AMI-CS by inducing an anterior myocardial infarction in vivo in a pig in order to generate the physiologic data required to develop a high-fidelity three-dimensional AMI-CS simulator. The CS state was confirmed by a combination of hemodynamic and laboratory data and the size of the infarct was confirmed thereafter by ex vivo staining techniques. We achieved our primary goal of ≥50% short-term survival post-infarction and induction of a CS state in 50% and therefore conclude that our model is sufficiently stable to warrant proceeding with the next phase of our program

<p>Uvod: Stratifikacija rizika je postala integralna komponenta savremenog pristupa tretmanu u kliničkoj praksi. Danas se u dijagnostici i lečenju akutnog infarkta miokarda (AIM) koriste različiti skorovi rizika kao prognostički instrumenti za kratkoročan i dugoročan ishod bolesti. Nužni proceduralni procesi, u toku primarne perkutane koronarne intervencije (pPKI), kao i saznanja o distribuciji i vrstama lezija koronarnih arterija su od velikog značaja, te se preporučuje finalna evaluacija rizika neposredno nakon izvr&scaron;ene pPKI. Metode istraživanja podataka omogućavaju pronalaženje skrivenih obrazaca u podacima, otkrivanje njihovih uzročno-posledičnih veza I odnosa, te razvoj savremenih prediktivnih modela. Cilj: Kreiranje i testiranje jednostavnog, praktičnog i u svakodnevnoj praksi upotrebljivog prediktivnog modela za procenu intra-hospitalnog ishoda lečenja pacijenata obolelih od AIM sa ST-elevacijom (STEMI) lečenih pPKI. Metode: Istraživanje je unicentrična, retrospektivna, ali I prospektivna studija. U retrospektivnu studiju je uključeno 1495 pacijenta sa STEMI koji su lečeni na Klinici za kardiologiju Instituta za kardiovaskularne bolesti Vojvodine (IKVBV) kod kojih je u cilju rekanalizacije infarktne arterije izvr&scaron;ena pPKI, u periodu od decembra 2008. godine do decembra 2011. godine. Svaki pacijent je inicijalno predstavljen sa 629 obeležja sadržanih u postojećem IKVBV informacionom sistemu, koja čine demografske karakteristike, podaci iz anamneze i kliničkog nalaza, parametri biohemijskih analiza krvi priprijemu, parametri ehokardiografskog pregleda, angiografski i proceduralni detalji i &scaron;ifre prijemnih dijagnoza. U svrhu istraživanja podataka kori&scaron;ćeno je programsko re&scaron;enje otvorenog koda Weka. Tokom evaluacije različitih algoritama izabran je algoritam koji daje najbolje rezultate po tačnosti predikcije i ROC parametru. U sklopu retrospektivnog dela izvr&scaron;ena je validacija prediktivnog modela&nbsp; desetostrukom unakrsnom validacijom na celom skupu podataka. Prospektivnom studijom je na uzorku od 400 pacijenata sa STEMI lečenih pPKI u toku 2015. godine izvr&scaron;ena dodatna validacija razvijenog prediktivnog modela. Za iste pacijente je izračunavat i GRACE skor rizika, te je upoređena njegova, i prediktivna moć razvijenog modela. Rezultati: Alternativno stablo odluke (ADTree) izdvojen je kao algoritam sa najboljim performansama u odnosu na ostale evaluirane algoritme. Cost sensitive klasifikacija je kori&scaron;ćena kao dodatna metodologija da bi se pojačala tačnost. ADTree stablo odluke izdvojilo je osam ključnih parametara koji najvi&scaron;e utiču na ishod intra-hospitalnog lečenja: sistolni krvni pritisak pri prijemu, ejekciona frakcija leve komore, udarni volumen leve komore, troponin, kreatinin fosfokinaza, ukupni bilirubin, T talas i<br />rezultat intervencije. Performanse razvijenog modela su: tačnost predikcije je 93.17%, ROC 0.94. Razvijeni model je na prospektivnoj validaciji zadržao performanse: tačnost predikcije 90.75%, ROC 0.93. &Scaron;iroko kori&scaron;ćeni GRACE skor je na prospektivnom skupu postigao ROC=0.86, &scaron;to pokazuje da je razvijeni prediktivni model superiorniji u odnosu na njega. Zaključak: Razvijeni prediktivni model je jednostavan i pouzdan. Njegova implementacija u svakodnevnu kliničku praksu, omogućila bi kliničarima da izdvoje visokorizične pacijente, nakon reperfuzionog tretmana, a potom kod njih intenziviraju tretman i kliničko praćenje, a sa ciljem smanjenja incidence intra-hospitalnih komplikacija i povećanja njihovog preživljavanja.</p> / <p>Introduction: Risk stratification has become an integral component of modern treatment in clinical practice. Today, the diagnosis and treatment of acute myocardial infarction (AMI) use different risk scores as a prognostic instruments for short-term and long-term outcome of the disease. The necessary procedural processes during primary percutaneous coronary intervention (pPCI) as well as knowledge about the distribution and types of lesions in coronary arteries are of great importance, and a final risk evaluation is recommended directly after the pPCI. Methods of data mining allow finding hidden patterns in data, disclosure of their causal connections and relationships, and the development of modern predictive models. Aim: To create and test a simple, practical and usable predictive model in daily practice for the&nbsp; assessment of intrahospital treatment outcome of patients with AMI with STsegment elevation (STEMI) treated with pPCI. Methods: Presented research is unicentric, retrospective but also prospective study. Retrospective study included 1495 patients with STEMI who were admitted to the Clinics of cardiology of the Institute of Cardiovascular Diseases Vojvodina (IKVBV). For the purpose of recanalization of the infarct artery, pPCI has been performed to these patients during the period from December 2008 to December 2011. Each patient was initially described with 629 attributes from the existing information system of IKVBV. Those attributes consist of demographic characteristics, data from history and clinical findings, biochemical parameters of blood tests on admission, the echocardiographic parameters, angiographic and procedural details and admission diagnosis codes. For model development, an open source software solution Weka was used. During the evaluation of different algorithms, algorithm that gives the best results in terms of accuracy and ROC parameter was chosen. As part of the retrospective study, in order to assess the models performance, ten-fold cross-validation on the entire data set was used. A prospective study, on a sample of 400 patients with STEMI, treated with pPCI in 2015, performed additional validation of the developed predictive model. GRACE risk score was calculated for the prospective study patients and comparison with the developed model has been performed. Results: Alternative decision tree (ADTree) was isolated as an algorithm with the best performance in relation to other algorithms evaluated. Cost sensitive classification was used as an additional methodology to enhance accuracy. ADTree selected eight key parameters that most influence the outcome of intra-hospital treatment: systolic blood pressure on admission, left ventricular ejection fraction, stroke volume of the left ventricle, troponin, creatine phosphokinase, total bilirubin, T wave and the result of the intervention. The performance of the developed model are: the accuracy of the prediction is 93.17%, ROC 0.94. The developed model kept its performance in prospective validation: accuracy of prediction 90.75%, ROC 0.93. Widely used GRACE score achieved ROC = 0.86 in the prospective study patients, indicating that developed predictive model is superior to him. Conclusion: Developed predictive model is simple and reliable. Its implementation in everyday clinical practice, would allow clinicians to distinguish high-risk patients after reperfusion treatment, and then for them to intensify treatment and clinical follow-up, with an aim of reducing the incidence of intra-hospital complications and increase their survival.</p>