<p>Tissue factor (TF) is the initiator of the coagulation cascade. Monocytes do not normally express TF, but can be induced to do so by certain stimuli. Aberrant TF expression is important in the thrombotic complications of bacterial sepsis, certain malignancies and coronary artery disease (CAD). In this thesis, regulation of monocyte TF by cytokines and by interactions with other vascular cells were studied, as well as the activation of blood cells, inflammation and coagulation in CAD patients and the association of the pro-inflammatory cytokine interleukin (IL)-6 with prognosis in unstable CAD. </p><p>In a whole blood experimental system, the anti-inflammatory cytokine IL-10 was shown to suppress lipopolysaccharide-induced TF expression in monocytes, whereas IL-4 and IL-13 did not, contrary to previous in vitro findings. Activated platelets also induced monocyte TF in whole blood in a P-selectin-dependent manner, causing a rapid surface exposure of TF independent of mRNA formation. The differentiated monocytic cell line U-937 displayed different kinetics of platelet-stimulated TF induction.</p><p>In co-culture with cytokine-activated human coronary artery endothelial cells, U-937 cells expressed TF, and also IL-6. The endothelial cells up-regulated their production of IL-10. Simvastatin, enalapril and dalteparin, all commonly used drugs in CAD treatment, suppressed TF induction but did not alter cytokine expression in co-cultures.</p><p>In unstable CAD, there was an activation of both coagulation and inflammation compared to stable CAD that coincided with an increased activation of platelets and leukocytes. Women had different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms.</p><p>Plasma levels of IL-6 above 5 ng/L proved to be a strong, independent marker for increased risk of death in a 6-12 month perspective in patients with unstable CAD. This risk was significantly reduced by an early invasive strategy.</p>

Tissue factor (TF) is the initiator of the coagulation cascade. Monocytes do not normally express TF, but can be induced to do so by certain stimuli. Aberrant TF expression is important in the thrombotic complications of bacterial sepsis, certain malignancies and coronary artery disease (CAD). In this thesis, regulation of monocyte TF by cytokines and by interactions with other vascular cells were studied, as well as the activation of blood cells, inflammation and coagulation in CAD patients and the association of the pro-inflammatory cytokine interleukin (IL)-6 with prognosis in unstable CAD. In a whole blood experimental system, the anti-inflammatory cytokine IL-10 was shown to suppress lipopolysaccharide-induced TF expression in monocytes, whereas IL-4 and IL-13 did not, contrary to previous in vitro findings. Activated platelets also induced monocyte TF in whole blood in a P-selectin-dependent manner, causing a rapid surface exposure of TF independent of mRNA formation. The differentiated monocytic cell line U-937 displayed different kinetics of platelet-stimulated TF induction. In co-culture with cytokine-activated human coronary artery endothelial cells, U-937 cells expressed TF, and also IL-6. The endothelial cells up-regulated their production of IL-10. Simvastatin, enalapril and dalteparin, all commonly used drugs in CAD treatment, suppressed TF induction but did not alter cytokine expression in co-cultures. In unstable CAD, there was an activation of both coagulation and inflammation compared to stable CAD that coincided with an increased activation of platelets and leukocytes. Women had different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms. Plasma levels of IL-6 above 5 ng/L proved to be a strong, independent marker for increased risk of death in a 6-12 month perspective in patients with unstable CAD. This risk was significantly reduced by an early invasive strategy.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p < 0.0001; diastolic: OR = 3.82, p < 0.0001), elevated fasting plasma glucose levels (OR = 8.84, p < 0.0001), hypertriglyceridaemia (OR = 22.16, p = 0.001), and obesity (body mass index OR = 0.89, p < 0.0001). Assessment of resting heart rate in clinical practice had minimal and non-significant additional prognostic value compared to established cardiovascular risk factors as judged by C statistics (C = 0.001, p = 0.979). Conclusion: The measurement of resting heart rate in the daily routine of primary care does not provide incremental prognostic information for cardiovascular risk stratification.

Orientador: Paula Schmidt Azevedo Gaiolla / Resumo: Introdução: Sabemos que o paciente que será submetido a procedimento cirúrgico estará sujeito ao estresse metabólico inerente ao próprio procedimento e às alterações na homeostase causadas pela doença de base. Assim, a avaliação e a terapia nutricional implementadas durante o perioperatório são de fundamental importância para que os indivíduos apresentem a melhor resposta possível a injúria decorrente da cirurgia, associada ao menor período de recuperação, de preferência sem complicações. A avaliação nutricional se mostra complexa a medida que leva em consideração vários fatores já que modernamente o conceito de desnutrição é amplo e avalia também o estado de inflamação sistêmico e não apenas o IMC. Em tempos nos quais temos cada vez mais pacientes obesos, porém desnutridos, uma avaliação ampla e multifatorial é imprescindível. Hoje contamos com escalas que nos ajudam a avaliar esses pacientes, entre elas o Nutritional Risk Screening (NRS) 2002, com medidas antropométricas e de composição corporal e a avaliação laboratorial, como por exemplo a dosagem da albumina. Objetivo: Criar um Manual e Protocolo de Avaliação Pré-operatória e de terapia nutricional no paciente cirúrgico a ser implantado e seguido no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Método: Foi realizada revisão da Literatura de artigos relevantes e Diretrizes Brasileiras e Internacionais, utilizando a base de dados Pubmed. As palavras e expressões chaves utilizadas foram: “ Preoperative risk sc... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: It´s known that the patient who will undergo a surgical procedure will be subject to the metabolic stress inherent in the procedure itself and the changes in homeostasis caused by the underlying disease. Thus, the evaluation and nutritional therapy implemented during the perioperative period are of fundamental importance for individuals to present the best possible response to injury due to surgery and the shortest recovery period, preferably without complications. Nutritional assessment is complex as it takes into account several factors, since the concept of malnutrition is broad and it also evaluates the state of systemic inflammation and not only BMI. Today, as we have a growing number of obese but malnourished patients, a comprehensive and multifactorial evaluation is essential. To make this evaluation possible we have scales that help us to evaluate these patients, among them the Nutritional Risk Screening (NRS) 2002, and the analysis of serum markers such as albumin. Objective: To create a Protocol for Pre-operative Evaluation and Nutritional Therapy in the surgical patient to be implanted and followed in the “Hospital das Clínicas da Faculdade de Medicina de Botucatu”. Method: The literature of relevant articles in Brazilian and International Guidelines hás been reviewed using the Pubmed database. Key words and phrases used were: "Preoperative risk screening", "Preoperative nutritional risk stratification", "Preoperative nutritional risk stratification",... (Complete abstract click electronic access below) / Mestre

Objectives: The inverse relationship between QT interval variability (QTV) and T wave amplitude potentially confounds QT variability assessment. We quantified the influence of the T wave amplitude on QTV in a comprehensive dataset and devised a correction formula. Methods: Three ECG datasets of healthy subjects were analyzed to model the relationship between T wave amplitude and QTV. To derive a generally valid correction formula, linear regression analysis was used. The proposed correction formula was applied to patients enrolled in the Evaluation of Defibrillator in Non-Ischemic Cardiomyopathy Treatment Evaluation trial (DEFINITE) to assess the prognostic significance of QTV for all-cause mortality in patients with non-ischemic dilated cardiomyopathy. Results: A strong inverse relationship between T wave amplitude and QTV was demonstrated, both in healthy subjects (R2 = 0.68, p < 0.001) and DEFINITE patients (R2 = 0.20, p < 0.001). Applying the T wave amplitude correction to QTV achieved 2.5-times better group discrimination between patients enrolled in the DEFINITE study and healthy subjects. Kaplan-Meier estimator analysis showed that T wave amplitude corrected QTVi is inversely related to survival (p < 0.01) and a significant predictor of all-cause mortality. Conclusion: We have proposed a simple correction formula for improved QTV assessment. Using this correction, predictive value of QTV for all-cause mortality in patients with non-ischemic cardiomyopathy has been demonstrated.

No description available.

Background: Several selected population-based studies have emphasized the significance of resting heart rate as an independent cardiovascular risk factor. However, there are no data available for using resting heart rate as a cardiovascular risk predictor in contemporary primary care. Thus, the aim of our analysis was to examine the clinical value of the measurement of resting heart rate in a large, unselected population-based cohort of primary care subjects under the conditions of contemporary primary prevention. Design: Prospective, population-based cohort study. Methods: We examined a subgroup of 5320 unselected primary care subjects free of coronary artery disease from the nationwide, longitudinal Diabetes Cardiovascular Risk Evaluation Targets and Essential Data for Commitment of Treatment (DETECT) cohort study, which was conducted from 2003 to 2008. Results: During the follow-up time of 5 years, 258 events were reported. Elevated resting heart rate was not associated with an increased risk for cardiovascular events (HR = 0.75, p = 0.394), cardiovascular mortality (HR = 0.71, p = 0.616) or major cardiovascular events (HR = 0.77, p = 0.376). By cross-sectional analysis, elevated heart rate clustered with markers of the metabolic syndrome, like increased blood pressure (systolic: OR = 5.54, p < 0.0001; diastolic: OR = 3.82, p < 0.0001), elevated fasting plasma glucose levels (OR = 8.84, p < 0.0001), hypertriglyceridaemia (OR = 22.16, p = 0.001), and obesity (body mass index OR = 0.89, p < 0.0001). Assessment of resting heart rate in clinical practice had minimal and non-significant additional prognostic value compared to established cardiovascular risk factors as judged by C statistics (C = 0.001, p = 0.979). Conclusion: The measurement of resting heart rate in the daily routine of primary care does not provide incremental prognostic information for cardiovascular risk stratification.

Endometriosis affect 11% of women of reproductive years worldwide. The project made use of lifestyle factors coming from the Lucy application. The Pearson correlation test was used to find linear correlation between endometriosis and lifestyle factors, while different machine learning models and logistic regression was used for finding non-linear correlations. The strongest linear correlation found (-0.23) was irregular menstruation however, the score does suggest a weak linear correlation. Decision Tree, Gradient boosted DT, XgBoost, Random Forest, and Logistic regression were usedto find patterns within the dataset. Risk stratification results proved to be unreliable. Decision Tree and its variants show strong evidence of correlation between endometriosis and the following features: weight, irregular menstruation, menstruation length, height, cycle length, irregular cycle, age, pregnancy, and daily symptoms. Additional analysis on those features could give more insight on what may be correlated as well as cause endometriosis. / Endometrios är en sjukdom som påverkar 11% av kvinnor i fortplantningsålder över hela världen. Det här projektet kommer använda livsstilsfaktorer som kommer från Lucy applikationen. Pearsons korrelations test används för att leta efter linjära korrelationer medans maskininlärnings modeller samt logistiskregression användes för att hitta icke-linjära korrelationer. Den starkaste linjärakorrelationen som hittades (-0.23) var oregelbunden menstruation, däremot tydervärdet på en svag linjär korrelation. Decision Tree, Gradient boosted DT, XgBoost, Random Forest, and Logistisk regressionsanalys användes för att hitta samband i datamängden. Riskstratifiering visades sig vara opålitliga. Decision Tree och deras varianter visade starka bevis på att det finns korrelationer mellan endometrios och följande egenskaper: vikt, oregelbunden menstruation, menstruationslängd, längd, cykellängd, oregelbunden cykel, ålder, graviditet samt dagliga symtomer. Mera analyser med dessa egenskaper kan ge mer insikt om vad som är korrelerat men även vad som orsakar endometrios

No description available.

Chest pain is one of the most common complaints amongst patients seeking urgent medical care at hospitals. Chest pain can be a symptom of serious cardiovascular disease such as acute coronary syndrome (ACS), however, most underlying causes are benign. Risk stratification in early stages of medical evaluation is difficult. As a consequence, many patients with chest pains are unnecessarily admitted to hospitals. There is precedent for using machine learning (ML) to aid in predicting cardiovascular disease. In this thesis, our goal is to investigate the feasibility of using ML as a complement to safely discharge patients. We use data collected by the ‘Clinical Expert Operating System - Chest Pain Danderyd Study’ (CLEOS-CPDS). Several models are developed to predict the risk of ACS following chest pains and for identifying important factors. Our best performing model on the highest risk class uses the random forest algorithm. The model has a recall score of 0.58 on the highest risk class using a subset of the medical history background. It admits 10 out of 12 patients who ultimately suffers from ACS, however, only 7 out of 12 are classified as high risk. Identified important features are mostly known risk factors, some of which are used in current risk calculations. However, less known factors such as chest pain radiation and associated symptoms, are also identified as important. The conclusion is that it is feasible to use a machine learning model to aid in risk stratification of ACS in early stages of evaluation, but that the current model needs improvement. In future work, a larger and more complete dataset with a longer follow-up period of patients may be highly beneficial to improve the model performance and verify the conclusions of this thesis. / En av de vanligaste orsakerna till att patienter söker akut sjukvård är bröstsmärta. Bröstsmärta kan vara ett symptom på livshotande sjukdom såsom akuta koronara syndrom (AKS), vilket innefattar hjärtinfarkt. Men i de allra flesta fall brukar orsakerna vara ofarliga. Det är svårt att bedöma bröstsmärtor i ett tidig skede och som en konsekvens utreds många patienter kanske i onödan, för att inte missa AKS. Vårt mål med den här rapporten är att utreda möjligheten att använda maskininlärning som stöd i riskbedömningen. Vi försöker identifiera viktiga faktorer i ett tidigt skede som kan hjälpa läkare att på ett säkert sätt utesluta allvarlig sjukdom. Detta görs genom att vi utvecklar flera maskininlärningsmodeller och jämför dessa mot varandra. Vi använder oss av data insamlad genom den pågående studien ‘Clinical Expert Operating System - Chest Pain Danderyd Study‘ (CLEOS-CPDS). Modellen bäst på att förutspå hög risk väljs sedan ut och analyseras närmare. Resultatet är en ‘Random Forest‘ modell. Modellen klassificerar åtminstone inläggning i 10 av 12 allvarliga fall, varav 7 av 12 fall klassificeras helt korrekt. Flera välkända riskfaktorer identifieras som viktiga, varav en del, men inte alla, redan ingår i nuvarande riskkalkyler. Vår slutsats är att det finns goda chanser att använda maskininlärning som ett komplement i sjukvården för att kunna utesluta allvarlig sjukdom, men att den nuvarande modellen behöver förbättras. För att säkerställa resultaten från denna rapport och förbättra modellen kan framtida undersökningar med fördel genomföras på mer data i fullständigare skick, samt med längre uppföljningstid på patienterna.