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The Canadian population is aging and issues related to the care of older adults are becoming increasingly common. The practice of general surgery is no stranger to this phenomenon, as older adults are increasingly presenting for surgery. Some 40% of these surgeries occur on a non-elective basis, which is associated with increased morbidity and mortality when compared to elective surgery. However, very little research has been done on prognostic factors for poor post-operative outcomes in older adults presenting for non-elective surgery. Thus, the purpose of this research is three-fold. First, to review the literature on prognostic factors for adverse outcomes in this patient population. Second, to examine prognostic factors associated with mortality in this patient population. Lastly, to examine prognostic factors associated with discharge to institution in this patient population.

Thesis (M.S.)--University of Michigan, 1968.

Thesis (M.S.)--University of Michigan, 1968.

Orientadores: Luiz Paulo Kowalski, Oslei Paes de Almeida / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-06T11:19:00Z (GMT). No. of bitstreams: 1 AguiarJunior_FranciscoCarlosAmanajasde_D.pdf: 897011 bytes, checksum: 668a5aef41289b1666790a45fcaabfc2 (MD5) Previous issue date: 2006 / Resumo: Neste trabalho, foram analisados os dados clinicopatológicos e a imunoexpressão de Ki-67, p53, bcl-2, FAS, Erb-B2, E-caderina e b-catenina em 27 carcinomas espinocelulares bucais (CEBs) de pacientes acometidos por recidiva local precoce, comparando-os com um grupo controle constituído por 54 pacientes com CEB sem história de recorrência, portadores de tumores de mesma localização e estadiamento clínico. Foram selecionados para este estudo 81 pacientes submetidos à cirurgia como primeiro tratamento no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital do Câncer, São Paulo/SP. Adicionalmente, em 17 CEBs foi realizada a comparação da imunoexpressão de Ki-67, p53, FAS, Erb-B2, E-caderina e b-catenina com suas respectivas recidivas locais precoces. Dentre todas variáveis analisadas, diferenças significativas no relato do consumo de álcool, na abordagem terapêutica instituída e na imunoexpressão de Ki-67, FAS e b-catenina (p=0.028, p=0.005, p=0.026 respectivamente) foram observadas. Uma fraca associação na imunomarcação por Ki-67, Erb-B2 (membrana), E-cadherin e b-catenin (ambos citoplasma) entre os CEBs e suas respectivas recidivas locais foi demonstrada, (índice kappa= 0.179, 0.337, 0.442 e 0.326 respectivamente). Os resultados obtidos sugerem que a imunoexpressão de Ki-67, FAS e b-catenina são potenciais marcadores do risco de desenvolvimento de recorrência local precoce do CEB e que a expressão de alguns biomarcadores analisados se altera nas recorrências locais / Abstract: In this study, the clinicopathological data and the immunoexpression of Ki-67, p53, bcl-2, FAS, Erb-B2, E-cadherin and b-catenin were analyzed in 27 oral squamous cell carcinoma (OSCC) of patients with early local recurrence compared with a control group composed by 54 patients with non-recurrent OSCC. All the patients in both groups were selected according to the tumor location and the clinical stage. The 81 patients assigned for this study had undergone surgery as the primary treatment at the Department of Head and Neck Surgery and Otorhinolaryngology, A.C. Camargo Cancer Hospital, São Paulo, Brazil. Additionally, a comparison was made between the immunoexpression of Ki-67, p53, bcl-2, FAS, Erb-B2, E-cadherin and b-catenin, and the early local recurrences in 17 cases. Among the variables studied, significant differences were observed in the report of alcohol consumption, the therapeutic assessment adopted, and the immunoexpression of Ki-67, FAS, Erb-B2 and b-catenin (p=0.028, p=0.005, p=0.026, respectively). There was no significant association in the immunoexpression of Ki-67, Erb-B2 (membrane), E-cadherin e b-catenin (both cytoplasmic) between the OSCCs and their corresponding early local recurrences (kappa index =0.179, 0.337, 0.442 e 0.326, respectively). The results obtained in this study suggest that the immunoexpresion of Ki-67, FAS e b-catenin are potential markers for the risk of early local recurrence, and thus the expression of some biomarkers analyzed changed in the recurrent tumor / Doutorado / Estomatologia / Doutor em Estomatopatologia

Abstract A population-based study was conducted to determine the trends in incidence and survival of cancer of the mobile tongue in Finland over the past 40 years. Possible changes in patient and tumour characteristics, early detection and prognostic factors of cancer of the mobile tongue were monitored in a geographically defined area of Northern Finland over the past 20 years. There were 1504 new cases with cancer of the mobile tongue in 1953-1994 in Finland and 105 cases in 1974-1994 in Northern Finland. An increasing trend in incidence of cancer of the mobile tongue was observed over the past 20 years both nationwide and in Northern Finland. The stage distribution of the cancer of the mobile tongue remained very much the same throughout the study period. Despite the increasing incidence rate and unchanged stage distribution of the tumours, the 5-year relative survival rate of cancer of the tongue improved from 40% to 58% in the 40-year study period in Finland. To evaluate the detection of cancer of the tongue, patients' primary care files were reviewed. It was revealed that the diagnostic skills of the physician/dentist first contacted by the patient had a significant effect on the patient's prognosis. If the cancer was not detected at the primary visit and no follow-up was scheduled, the delay was often fatally long. The most important factor influencing the referral pattern was the patient's primary symptom at the initial visit. The more closely the symptom was related to the tongue, the more likely the patient was correctly referred. To recognise aggressively behaving early stage (Stages I-II) cancers of the tongue, various prognostic factors were analysed. It was observed that an old age (65+years) of the patient, a high malignancy score of the tumour and the absence of p53 predicted poor prognosis in early stage carcinomas. Patients with these qualities may require more aggressive initial therapy.

Abstract This research was designed to assess the prevalence, characteristics, natural course and autonomic regulation of ectopic atrial tachycardia (EAT) and inappropriate sinus tachycardia (IST) and the response of IST to adenosine. The prevalence of EAT, as estimated from the electrocardiograms (ECG) of males applying for a pilot's licence, was 0.34%. During a mean follow-up time of 8 years among 10 asymptomatic subjects and 7 years among 17 symptomatic patients, a majority of the subjects showed a reduction of the heart rate (HR), either with restoration of sinus rhythm (SR) (37%) or with a change in P wave morphology (37%). The prevalence of IST in a random sample of 604 middle-aged subjects was 1.16%. The systolic and diastolic ambulatory blood pressures were higher among the subjects with IST than subjects with SR (P < 0.001). The other laboratory, echocardiographic and personality measurements, with the exception of the hostility score (P < 0.001), revealed no differences between the groups. During a mean follow-up of 6 years, none of the subjects with IST developed any evidence of structural heart disease despite ongoing palpitations, and there was no significant reduction of the 24-hour average HR. In an analysis of R-R interval variability from 24-hour ECG recordings in 12 patients with incessant EAT, 12 subjects with IST and 24 subjects with SR, the time- and frequency-domain measures of HR variability did not differ between the subjects with EAT and IST. However, the short-term fractal HR behaviour differed between EAT and IST. In studies of the effects of adenosine in 18 patients with IST and 18 subjects with SR, adenosine prolonged significantly the sinus interval (P < 0.001) in the control subjects, but did not cause any significant changes of atrial cycle length in the patients with IST. Conclusions: 1. EAT has a tendency towards gradual degeneration over time. 2. The prevalence of IST is higher than previously assumed, but the overall prognosis is good. 3. EAT and IST seem to be under similar autonomic regulation as the sinus node, but the firing of ectopic atrial foci shows more random behaviour. 4. The usual negative chronotropic effect of adenosine is impaired in subjects with IST.

Background Research on the optimal management of deceased organ donors poses unique challenges including the fact that one deceased donor may provide up to 8 organs for transplantation. Measuring the post-transplant function of these organs – good or bad – represents an attractive way of deciding whether treatment of deceased donors is working well, or not so well. Function, however, is organ-specific. Therefore, to conduct the most efficient and informative research on deceased donor management, we need an outcome measure that works well in all organs. The new outcome measure is called Generic Rating of Allograft Function post-Transplantation (GRAFT). Methods In this thesis, I highlight the methods for developing the cardiac-specific version of the GRAFT instrument. The same methods, however, have and will be applied to other organ-specific versions. The work comprised various study designs and developed novel research tools, all of which have advanced the development of the GRAFT instrument. At first, we developed a simple conceptualization for the instrument. Through regular consultation with research methodologists, biostatisticians and clinical experts, we refined the fundamental conceptualization and then refined the generic instrument, itself. One key concept is that GRAFT ratings should correlate with one-year graft function. To maximize its utility, I developed a heart--specific guide for applying GRAFT in future studies, and other organ-specific guides are underway. Specifically, we developed these guides by identifying the most robust predictors of one-year graft function through the conduct of organ-specific systematic reviews and meta-analyses of prognostic factors. The evidence from these reviews, in consultation with a focus group of organ-specific transplant physicians, lead to refinements of our guides. We subsequently conducted a mixed-methods user testing to assess reliability and usability of the organ-specific guides. In appraising the evidence informing the guides, we developed GRADE guidance and a novel absolute risk calculator to assess our certainty in the body of evidence on prognostic factors informing our guides. Results We developed a 6-point generic rating instrument for classification of graft function to be applied post-transplant across all major solid organs. We designed GRAFT to be applied at the time of discharge, 1-month post-transplant, or at the time of death (whichever occurs first). We classify function as 1) normal, 2A) impaired but likely to gain normal function, 2B) impaired and unlikely to gain normal function, 3A) severely impaired but likely to gain some function, 3B) severely impaired and unlikely to gain some function, and 4) irreversible graft failure. Clinical expert collaborators for each organ type confirmed face validity of the GRAFT instrument. For all organs, we identified a number of prognostic factors that can guide users in classifying organ function post-transplant. In consultation with clinical experts, we determined that the most important factor is graft function as measured by left ventricular ejection fraction (LVEF) or right atrial pressure (RAP). Due to limitations with the quality and quantity of the evidence, however, the heart transplant experts did not rely on the results of their organ group’s systematic review. In turn, we conducted a retrospective cohort study to calculate the best estimate of association between LVEF, RAP, and overall mortality post heart transplant. For the cardiac version of GRAFT, user testing demonstrated high reliability (Kappa of 0.87, 95% CI 0.62 – 1.00) and acceptable usability (system usability score of 75, inter-quartile range of 72.5 – 80). In the process, we developed and published GRADE guidance for assessing certainty in the body of evidence addressing prognostic factors and devised a calculator to transform relative effect of each prognostic factor to absolute risks (http://hiru.mcmaster.ca/AbsoluteRiskCalculator/). Conclusion In this thesis, I advanced the development of an innovative generic instrument for the classification of graft function specifically for the purpose of application in clinical trials of deceased donor interventions. This work is ongoing, but very advanced for heart-specific components, for which I have ensured face validity, and demonstrated reliability and usability. The GRAFT instrument may better facilitate the conduct of future research to improve care of deceased organ donors with a view to improving quality and quantity of organs for transplantation. / Thesis / Candidate in Philosophy

High expression levels of the gene BAALC (brain and acute leukemia, cytoplasmic) are associated with poor prognosis in acute myeloid leukemia (AML) patients, but the underlying mechanisms are not yet understood. We evaluated the prognostic significance of expression levels of miR-3151, a newly discovered microRNA embedded in intron 1 of the BAALC gene, in a cohort of 179 older (≥60 years) cytogenetically normal AML (CN-AML) patients, in the context of established molecular markers and especially with regard to the possible interplay with its host gene BAALC. In multivariable analyses, high miR-3151 was associated with shorter disease-free and overall survival (OS), while higher BAALC expression strongly predicted failure of complete remission attainment and OS. Patients exhibiting both high miR-3151 and BAALC expression had worse outcome than patients expressing low levels of either one of the genes or both. Next, gene - and microRNA-expression profiles associated with miR-3151 expression were derived using microarrays, and a pathway analysis of the miR-3151 associated gene signature was performed using Ingenuity software. High miR-3151 expressers showed downregulation of genes involved in transcriptional regulation, post-translational modifications and cell-cycle control. Two genes of the ubiquitination pathway, FBXL20 and USP40, were experimentally validated as direct miR-3151 targets. In summary, we identified high expression levels of the intronic miR-3151 as a novel, independent prognosticator for poor outcome in CN-AML. Interestingly, miR-3151 impacted differently on outcome than its host gene BAALC; and the combination of both markers identified a patient subset with the poorest outcome, suggesting that the microRNA and its host gene contribute to clinical and prognostic features of CN-AML independently and through distinct mechanisms. This is the first example of the interplay of an intronic miR and its host gene in leukemia. Its discovery may have important biologic implications for future targeted treatment strategies.

published_or_final_version / abstract / Medicine / Master / Doctor of Medicine