In this project stroke data were analyzed with the use of survival techniques and incomplete principal component cox analysis. The data set resulted from a multi-center randomised controlled trial coordinated by investigators from the Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton with 438 patients. It was found that among stroke survivors, congestive heart failure along with other cardiac impairments post the major risks. Other factors found to be important were patient age, previous TIAs, presence of ulcers, diabetes and sex. / Thesis / Master of Science (MS)

Au travers d’études cliniques et biologiques, de méta-analyses et de revues systématiques de la littérature, nous avons étudié les CBNPC de stade III sur le plan thérapeutique et cherché des facteurs pronostiques pour la survie dans le but d’améliorer la classification internationale et, à terme, de permettre une meilleure prise en charge des patients inclus dans ce groupe hétérogène de tumeurs. Dans le cadre d’essais randomisés, nous avons montré qu’un abord multimodal et multidisciplinaire permettait d’améliorer le pronostic des patients atteints d’un CBNPC de stade III. Le traitement des tumeurs non résécables implique une combinaison de chimiothérapie et de radiothérapie, dont l’administration concomitante doit être proposée aux patients aptes à la tolérer. La chimiothérapie doit être incluse dans le schéma thérapeutique des tumeurs potentiellement résécables. Elle permet une résection chirurgicale complète chez des patients sélectionnés dont la tumeur était initialement non résécable. Nous avons déterminé que des caractéristiques cliniques (l’indice de performance et l’âge), biologiques (les taux sanguins de polynucléaires neutrophiles, d’hémoglobine et de plaquettes, la bilirubinémie) et propres à la tumeur (l’extension locale [T3-4] et ganglionnaire [N3]) avaient une valeur pronostique indépendante pour la survie. Ceci nous a permis d’aboutir à une proposition de modification de la classification internationale concernant les CBNPC de stade III. Bien que pris individuellement, les facteurs biologiques que nous avons étudiés (p53, EGF-R, TTF-1, Mdm2) n’aient pas de valeur pronostique pour la survie, nous avons montré que la combinaison EGF-R+/TTF1- était un facteur pronostique indépendant en analyse multivariée pour la survie spécifique au cancer bronchique. Nous avons finalement évalué le rôle pronostique de la tomodensitométrie par émission de positrons et de la mesure semi-quantitative de captation du 18F-FDG (SUV) sur la survie des patients atteints de CBNPC et montré qu’un SUV élevé était un facteur de mauvais pronostic pour la survie.

No description available.

No description available.

Racional: Aproximadamente um de cada cinco pacientes hospitalizados por pneumonia adquirida na comunidade (PAC) apresenta uma resposta clínica inadequada, sendo a mortalidade nestes pacientes de 40%. Os objetivos do estudo foram: determinar a incidência e as variáveis de associação independente com fracasso terapêutico da PAC, e os fatores prognósticos da PAC tratada em ambiente hospitalar. Métodos: Estudo de coorte, prospectivo, multicêntrico, com 425 pacientes hospitalizados por PAC. Os pacientes foram acompanhados de forma sistemática para identificação do fracasso terapêutico e seguidos até a alta hospitalar. Resultados: A incidência de fracasso terapêutico foi de 14,6% (62/425). Os preditores independentes de risco para o fracasso foram: insuficiência renal aguda à admissão (OR 2,9; IC 95% 1,2-7,2; p=0,017), progressão radiológica (OR 29,8; IC 95 8,1-109,7%; p<0,001), derrame pleural (OR 3,4; IC 95% 1,3-8,6; p=0,010), relação PaO2/FiO2 inferior a 250 à admissão (OR 2,7; IC 95% 1,1-6,7; p=0,017) e PSI classe V (OR 2,7; IC 95% 1,1-7,0; p=0,042). A mortalidade geral foi de 7,5%, e de 40,3% nos pacientes com fracasso. O fracasso terapêutico foi o principal fator independente de mortalidade na PAC (OR 85,3, IC 95% 18,8-387,4, p<0,0001). Conclusão: O fracasso terapêutico da PAC é freqüente, está associado a marcadores clínicos, radiológicos e laboratoriais identificáveis desde a admissão hospitalar (ou nos primeiros dias de acompanhamento), sendo o principal preditor independente de mortalidade. / Rational: One out of five patients hospitalized for community-acquired pneumonia (CAP) might have an inadequate response to empirical antimicrobial treatment, and the mortality among these patients may reach rates of up to 40%. The aims of the study were to: quantify the incidence of empirical treatment failure in CAP, identify risk factors for therapeutic failure and prognostic factors in CAP. Methods: Prospective, multicenter cohort study of 425 hospitalized patients for CAP. The systematic identification of treatment failure required a daily follow-up until hospital discharge. Results: The incidence of treatment failure was 14.6% (62/425). The independent risk factors associated with therapeutic failure in a logistic analysis were: acute renal failure (OR 2.9; 95% CI 1.2-7.2; p=0.017), radiological progression (OR 29.8; IC 95 8.1-109.7%; p<0.001), pleural effusion (OR 3.4; 95% CI 1.3-8.6; p=0.010), PaO2/FiO2 ratio < 250 (OR 2.7; 95% CI 1.1-6.7; p=0.017) e pneumonia severity index Class V (OR 2.7; 95% CI 1.1-7.0; p=0.042). Mortality was significantly higher in patients with therapeutic failure (40.3% vs. 7.5%). Treatment failure was the main prognostic factor associated with CAP (OR 85.3; 95% CI 18.8-387.4, p<0.0001). Conclusion: The treatment failure is frequently found and it is associated with clinical, radiological and laboratorial markers. It is also an important independent predictor of mortality in CAP.

Racional: Aproximadamente um de cada cinco pacientes hospitalizados por pneumonia adquirida na comunidade (PAC) apresenta uma resposta clínica inadequada, sendo a mortalidade nestes pacientes de 40%. Os objetivos do estudo foram: determinar a incidência e as variáveis de associação independente com fracasso terapêutico da PAC, e os fatores prognósticos da PAC tratada em ambiente hospitalar. Métodos: Estudo de coorte, prospectivo, multicêntrico, com 425 pacientes hospitalizados por PAC. Os pacientes foram acompanhados de forma sistemática para identificação do fracasso terapêutico e seguidos até a alta hospitalar. Resultados: A incidência de fracasso terapêutico foi de 14,6% (62/425). Os preditores independentes de risco para o fracasso foram: insuficiência renal aguda à admissão (OR 2,9; IC 95% 1,2-7,2; p=0,017), progressão radiológica (OR 29,8; IC 95 8,1-109,7%; p<0,001), derrame pleural (OR 3,4; IC 95% 1,3-8,6; p=0,010), relação PaO2/FiO2 inferior a 250 à admissão (OR 2,7; IC 95% 1,1-6,7; p=0,017) e PSI classe V (OR 2,7; IC 95% 1,1-7,0; p=0,042). A mortalidade geral foi de 7,5%, e de 40,3% nos pacientes com fracasso. O fracasso terapêutico foi o principal fator independente de mortalidade na PAC (OR 85,3, IC 95% 18,8-387,4, p<0,0001). Conclusão: O fracasso terapêutico da PAC é freqüente, está associado a marcadores clínicos, radiológicos e laboratoriais identificáveis desde a admissão hospitalar (ou nos primeiros dias de acompanhamento), sendo o principal preditor independente de mortalidade. / Rational: One out of five patients hospitalized for community-acquired pneumonia (CAP) might have an inadequate response to empirical antimicrobial treatment, and the mortality among these patients may reach rates of up to 40%. The aims of the study were to: quantify the incidence of empirical treatment failure in CAP, identify risk factors for therapeutic failure and prognostic factors in CAP. Methods: Prospective, multicenter cohort study of 425 hospitalized patients for CAP. The systematic identification of treatment failure required a daily follow-up until hospital discharge. Results: The incidence of treatment failure was 14.6% (62/425). The independent risk factors associated with therapeutic failure in a logistic analysis were: acute renal failure (OR 2.9; 95% CI 1.2-7.2; p=0.017), radiological progression (OR 29.8; IC 95 8.1-109.7%; p<0.001), pleural effusion (OR 3.4; 95% CI 1.3-8.6; p=0.010), PaO2/FiO2 ratio < 250 (OR 2.7; 95% CI 1.1-6.7; p=0.017) e pneumonia severity index Class V (OR 2.7; 95% CI 1.1-7.0; p=0.042). Mortality was significantly higher in patients with therapeutic failure (40.3% vs. 7.5%). Treatment failure was the main prognostic factor associated with CAP (OR 85.3; 95% CI 18.8-387.4, p<0.0001). Conclusion: The treatment failure is frequently found and it is associated with clinical, radiological and laboratorial markers. It is also an important independent predictor of mortality in CAP.

Racional: Aproximadamente um de cada cinco pacientes hospitalizados por pneumonia adquirida na comunidade (PAC) apresenta uma resposta clínica inadequada, sendo a mortalidade nestes pacientes de 40%. Os objetivos do estudo foram: determinar a incidência e as variáveis de associação independente com fracasso terapêutico da PAC, e os fatores prognósticos da PAC tratada em ambiente hospitalar. Métodos: Estudo de coorte, prospectivo, multicêntrico, com 425 pacientes hospitalizados por PAC. Os pacientes foram acompanhados de forma sistemática para identificação do fracasso terapêutico e seguidos até a alta hospitalar. Resultados: A incidência de fracasso terapêutico foi de 14,6% (62/425). Os preditores independentes de risco para o fracasso foram: insuficiência renal aguda à admissão (OR 2,9; IC 95% 1,2-7,2; p=0,017), progressão radiológica (OR 29,8; IC 95 8,1-109,7%; p<0,001), derrame pleural (OR 3,4; IC 95% 1,3-8,6; p=0,010), relação PaO2/FiO2 inferior a 250 à admissão (OR 2,7; IC 95% 1,1-6,7; p=0,017) e PSI classe V (OR 2,7; IC 95% 1,1-7,0; p=0,042). A mortalidade geral foi de 7,5%, e de 40,3% nos pacientes com fracasso. O fracasso terapêutico foi o principal fator independente de mortalidade na PAC (OR 85,3, IC 95% 18,8-387,4, p<0,0001). Conclusão: O fracasso terapêutico da PAC é freqüente, está associado a marcadores clínicos, radiológicos e laboratoriais identificáveis desde a admissão hospitalar (ou nos primeiros dias de acompanhamento), sendo o principal preditor independente de mortalidade. / Rational: One out of five patients hospitalized for community-acquired pneumonia (CAP) might have an inadequate response to empirical antimicrobial treatment, and the mortality among these patients may reach rates of up to 40%. The aims of the study were to: quantify the incidence of empirical treatment failure in CAP, identify risk factors for therapeutic failure and prognostic factors in CAP. Methods: Prospective, multicenter cohort study of 425 hospitalized patients for CAP. The systematic identification of treatment failure required a daily follow-up until hospital discharge. Results: The incidence of treatment failure was 14.6% (62/425). The independent risk factors associated with therapeutic failure in a logistic analysis were: acute renal failure (OR 2.9; 95% CI 1.2-7.2; p=0.017), radiological progression (OR 29.8; IC 95 8.1-109.7%; p<0.001), pleural effusion (OR 3.4; 95% CI 1.3-8.6; p=0.010), PaO2/FiO2 ratio < 250 (OR 2.7; 95% CI 1.1-6.7; p=0.017) e pneumonia severity index Class V (OR 2.7; 95% CI 1.1-7.0; p=0.042). Mortality was significantly higher in patients with therapeutic failure (40.3% vs. 7.5%). Treatment failure was the main prognostic factor associated with CAP (OR 85.3; 95% CI 18.8-387.4, p<0.0001). Conclusion: The treatment failure is frequently found and it is associated with clinical, radiological and laboratorial markers. It is also an important independent predictor of mortality in CAP.

Abstract Incidence trends of laryngeal cancer in Finland were analyzed, especially in relation to survival, in a patient series of 5766 patients diagnosed in 1956–1995 and identified from the Finnish Cancer Registry. The age-adjusted incidence rate decreased from 6.5 to 3.5 per 100 000 person-years in males and remained unchanged among females. Only minor improvement occurred in survival. In a hospital-based material from Northern Finland (353 patients with laryngeal squamocellular carcinoma, LSCC, diagnosed in 1976–1995), the incidence among males decreased only for supraglottic cancer, diminishing the supraglottic to glottic incidence ratio from 1.4:1 to 0.5:1. Evaluation of diagnostic delays and their impact on survival and risk of recurrence was undertaken in a sample of 66 LSCC patients. In only 38% of the patients was malignancy suspected at the initial visit to a physician; infection was the most common misdiagnosis (41%). Half of the first consultations resulted in referral, whereas 17% of the patients were neither referred nor controlled. The median patient delay was 2 months and median professional delay 3 months. The latter exceeded 12 months in 17% of the patients. The delays were not significantly related to any other clinical parameter, nor were they interrelated. Professional delay of 12 months or more resulted in increased relative hazard of death (HR = 4.74, p = 0.05), equalling the effect of advanced stage (stage IV). One-third of the patients developed a recurrence. In univariate analysis, professional delay of 12 months or more increased the risk of local (p = 0.019) and neck (p = 0.019) recurrence. In a multivariate model, professional delay of 12 months or more indicated an adjusted relative hazard ratio (HR) of 4.6 for local recurrence (p = 0.02) and 9.5 for neck recurrence (p = 0.015). Immunohistochemical factors p53, apoptosis, angiogenesis and proliferation were included in a multivariate model evaluating prognostic factors of LSCC in addition to clinical and sociodemographic factors. Advanced stage (stages III–IV) (relative hazard ratio of death (HR) 8.9, p = 0.01), supraglottic site (HR 5.6, p = 0.02) and high apoptotic index (≥ 0.3) (HR 11.1, p = 0.05) were the best indicators of impaired prognosis. Professional delay and enhanced apoptotic rate could be helpful in selecting LSCC patients for more aggressive primary treatment.

Reprinted from Cancer Biomarkers, 15(4), Nakashima et al., Urine CXCL1 as a biomarker for tumor detection and outcome prediction in bladder cancer, 357-364, Copyright (2015), with permission from IOS Press. / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19596号 / 医博第4103号 / 新制||医||1014(附属図書館) / 32632 / 京都大学大学院医学研究科医学専攻 / (主査)教授 椛島 健治, 教授 武田 俊一, 教授 川村 孝 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23808号 / 医博第4854号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長尾 美紀, 教授 西浦 博, 教授 朝長 啓造 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM