Introdução: O Red blood cell distribution width (RDW) é um preditor de mortalidade em pacientes criticamente enfermos. A associação do RDW na alta da UTI com o risco de readmissão à UTI não é conhecida. Nós fizemos este estudo com o objetivo de investigar a associação entre a presença de anisocitose na alta da UTI e o risco de readmissão à UTI ou óbito inesperado na enfermaria. Métodos: Estudo de coorte retrospectivo que incluiu 813 pacientes com alta da UTI para a enfermaria em um hospital terciário de Porto Alegre, Brasil. A variável de interesse foi o RDW coletado no momento da alta da UTI. Anisocitose foi definida como RDW > 16%. Desfechos de interesse foram readmissão à UTI, óbito inesperado na enfermaria e óbito hospitalar. Hazard ratios (HR) foram estimadas usando o Modelo de Riscos proporcionais de Cox. Variáveis com P < 0.1 na análise univariada foram incluídas na análise multivariada para ajuste. Resultados: Anisocitose na alta da UTI está independentemente associada com readmissão à UTI ou óbito inesperado na enfermaria (HR: 1,682; IC 95% 1,219 – 2,322; P = 0,002). Outras variáveis associadas com este desfecho foram: idade, escore Sequential Organ Failure Assessment (SOFA) na alta da UTI e traqueostomia. Resultados significativos semelhantes foram obtidos após exclusão dos óbitos inesperados na enfermaria (HR: 2,031; IC 95% 1,428 – 2,889; P< 0,001) e para óbito hospitalar (HR: 1,716; IC 95% 1,141 – 2,580; P = 0,01). Conclusões: Anisocitose no momento da alta da UTI está independentemente associada com readmissão à UTI e óbito hospitalar. / Introduction: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. The relationship between the RDW at ICU discharge and the risk of ICU readmission is unknown. The purpose of this study was to investigate the association between the presence of anisocytosis at ICU discharge and the risk of ICU readmission or unexpected death in the ward. Methods: This retrospective cohort study included 813 patients discharged alive from the ICU to the ward in a tertiary hospital in Porto Alegre, Brazil. The target variable was the RDW collected at the time of ICU discharge. Anisocytosis was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Variables with a value of P < 0.1 in the univariate analysis were included in the multivariate analysis for adjustment. Results: Anisocytosis at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward (HR: 1.682; 95% CI 1.219-2.322; P = 0.002). Other variables associated with this outcome included age, Sequential Organ Failure Assessment (SOFA) score at ICU discharge and tracheostomy. Similar significant results were obtained after the exclusion of unexpected deaths in the ward (HR 2.031; CI 1.428 – 2.889; P < 0.001) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580; P = 0.01). Conclusions: Anisocytosis at ICU discharge is independently associated with ICU readmission and in-hospital death.

Introdução: O Red blood cell distribution width (RDW) é um preditor de mortalidade em pacientes criticamente enfermos. A associação do RDW na alta da UTI com o risco de readmissão à UTI não é conhecida. Nós fizemos este estudo com o objetivo de investigar a associação entre a presença de anisocitose na alta da UTI e o risco de readmissão à UTI ou óbito inesperado na enfermaria. Métodos: Estudo de coorte retrospectivo que incluiu 813 pacientes com alta da UTI para a enfermaria em um hospital terciário de Porto Alegre, Brasil. A variável de interesse foi o RDW coletado no momento da alta da UTI. Anisocitose foi definida como RDW > 16%. Desfechos de interesse foram readmissão à UTI, óbito inesperado na enfermaria e óbito hospitalar. Hazard ratios (HR) foram estimadas usando o Modelo de Riscos proporcionais de Cox. Variáveis com P < 0.1 na análise univariada foram incluídas na análise multivariada para ajuste. Resultados: Anisocitose na alta da UTI está independentemente associada com readmissão à UTI ou óbito inesperado na enfermaria (HR: 1,682; IC 95% 1,219 – 2,322; P = 0,002). Outras variáveis associadas com este desfecho foram: idade, escore Sequential Organ Failure Assessment (SOFA) na alta da UTI e traqueostomia. Resultados significativos semelhantes foram obtidos após exclusão dos óbitos inesperados na enfermaria (HR: 2,031; IC 95% 1,428 – 2,889; P< 0,001) e para óbito hospitalar (HR: 1,716; IC 95% 1,141 – 2,580; P = 0,01). Conclusões: Anisocitose no momento da alta da UTI está independentemente associada com readmissão à UTI e óbito hospitalar. / Introduction: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. The relationship between the RDW at ICU discharge and the risk of ICU readmission is unknown. The purpose of this study was to investigate the association between the presence of anisocytosis at ICU discharge and the risk of ICU readmission or unexpected death in the ward. Methods: This retrospective cohort study included 813 patients discharged alive from the ICU to the ward in a tertiary hospital in Porto Alegre, Brazil. The target variable was the RDW collected at the time of ICU discharge. Anisocytosis was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Variables with a value of P < 0.1 in the univariate analysis were included in the multivariate analysis for adjustment. Results: Anisocytosis at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward (HR: 1.682; 95% CI 1.219-2.322; P = 0.002). Other variables associated with this outcome included age, Sequential Organ Failure Assessment (SOFA) score at ICU discharge and tracheostomy. Similar significant results were obtained after the exclusion of unexpected deaths in the ward (HR 2.031; CI 1.428 – 2.889; P < 0.001) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580; P = 0.01). Conclusions: Anisocytosis at ICU discharge is independently associated with ICU readmission and in-hospital death.

Introdução: A pré-eclâmpsia é uma das principais causas de mortalidade materna e perinatal em todo o mundo. A relação entre a amplitude de distribuição das hemácias (Red Cell Distribution Width - RDW) e hipertensão arterial já está bem documentada, porém há uma escassez de dados relacionando RDW com pré-eclâmpsia. Material e métodos: Estudo observacional analítico retrospectivo, realizado no período de 2014 e 2015, composto por 108 participantes no grupo de estudo (50 pré-eclâmpsia leve e 58 pré-eclâmpsia grave) e 101 participantes no grupo controle. A hemoglobina, RDW, plaquetas e outros índices hematológicos foram medidos como parte do hemograma automatizado. Resultados: Não houve diferença no RDW entre as gestantes do grupo controle e grupo com pré-eclâmpsia leve (14,68 ± 1,64 vs. 14,22 ± 1,87; p=0,385), grupo controle e grupo com pré-eclâmpsia grave (14,68 ± 1,64 vs. 14,24 ± 1,78; p=0,386) e grupo controle e grupo com pré-eclâmpsia (14,68 ± 1,64 vs. 14,23 ± 1,81; p=0,063). Conclusão: Os níveis de RDW sérico materno não estão associados com a presença da pré-eclâmpsia e os graus de gravidade da doença. / Introduction: Preeclampsia is one of the main causes of the maternal and perinatal mortality all over the world. The relationship between the amplitude of red cells distribution (Red Cell Distribution Width – RDW) and arterial hypertension is already well documented, though there is a shortage of data relating RDW with preeclampsia. Methods: Analytical observational study conducted in the years 2014 and 2015, composed by 108 patients in the study group (50 mild preeclampsia and 58 severe preeclampsia) and 101 patients in the control group. The hemoglobin, RDW, platelets and other hematological indices were measured as part of the automated hemogram. Results: There was no difference in RDW between the pregnant women in the control group and the ones in the mild preeclampsia group (14,68 ± 1,64 vs. 14,22 ± 1,87), the control group and the severe preeclampsia group (14,68 ± 1,64 vs. 14,24 ± 1,78) and the control group and preeclampsia group (14,68 ± 1,64 vs. 14,23 ± 1,81). Conclusion: The levels of maternal serum RDW are not associated with the presence of preeclampsia and the levels of its severity. / Dissertação (Mestrado)

Introdução: O Red blood cell distribution width (RDW) é um preditor de mortalidade em pacientes criticamente enfermos. A associação do RDW na alta da UTI com o risco de readmissão à UTI não é conhecida. Nós fizemos este estudo com o objetivo de investigar a associação entre a presença de anisocitose na alta da UTI e o risco de readmissão à UTI ou óbito inesperado na enfermaria. Métodos: Estudo de coorte retrospectivo que incluiu 813 pacientes com alta da UTI para a enfermaria em um hospital terciário de Porto Alegre, Brasil. A variável de interesse foi o RDW coletado no momento da alta da UTI. Anisocitose foi definida como RDW > 16%. Desfechos de interesse foram readmissão à UTI, óbito inesperado na enfermaria e óbito hospitalar. Hazard ratios (HR) foram estimadas usando o Modelo de Riscos proporcionais de Cox. Variáveis com P < 0.1 na análise univariada foram incluídas na análise multivariada para ajuste. Resultados: Anisocitose na alta da UTI está independentemente associada com readmissão à UTI ou óbito inesperado na enfermaria (HR: 1,682; IC 95% 1,219 – 2,322; P = 0,002). Outras variáveis associadas com este desfecho foram: idade, escore Sequential Organ Failure Assessment (SOFA) na alta da UTI e traqueostomia. Resultados significativos semelhantes foram obtidos após exclusão dos óbitos inesperados na enfermaria (HR: 2,031; IC 95% 1,428 – 2,889; P< 0,001) e para óbito hospitalar (HR: 1,716; IC 95% 1,141 – 2,580; P = 0,01). Conclusões: Anisocitose no momento da alta da UTI está independentemente associada com readmissão à UTI e óbito hospitalar. / Introduction: Red blood cell distribution width (RDW) is a predictor of mortality in critically ill patients. The relationship between the RDW at ICU discharge and the risk of ICU readmission is unknown. The purpose of this study was to investigate the association between the presence of anisocytosis at ICU discharge and the risk of ICU readmission or unexpected death in the ward. Methods: This retrospective cohort study included 813 patients discharged alive from the ICU to the ward in a tertiary hospital in Porto Alegre, Brazil. The target variable was the RDW collected at the time of ICU discharge. Anisocytosis was defined as an RDW > 16%. Outcomes of interest included readmission to the ICU, unexpected death in the ward and in-hospital death. Hazard ratios (HR) were estimated using the Cox proportional hazards model. Variables with a value of P < 0.1 in the univariate analysis were included in the multivariate analysis for adjustment. Results: Anisocytosis at ICU discharge was independently associated with readmission to the ICU or unexpected death in the ward (HR: 1.682; 95% CI 1.219-2.322; P = 0.002). Other variables associated with this outcome included age, Sequential Organ Failure Assessment (SOFA) score at ICU discharge and tracheostomy. Similar significant results were obtained after the exclusion of unexpected deaths in the ward (HR 2.031; CI 1.428 – 2.889; P < 0.001) and for in-hospital deaths (HR 1.716; 95% CI 1.141-2.580; P = 0.01). Conclusions: Anisocytosis at ICU discharge is independently associated with ICU readmission and in-hospital death.

Introduction: Acute myeloid leukemia (AML) is a highly heterogeneous disease which renders risk stratification at diagnosis of high importance to personalize therapy. Allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance for sustained remission in most AML patients, but usually comes at the risk of a significant treatment-related mortality. The red cell distribution width (RDW) is an universally accessible parameter that identifies individuals with a higher mortality in many diseases, including some hematological entities. However, the impact of diagnostic RDW levels in AML – especially in the context of a HSCT consolidation - has not been evaluated so far. Purpose: To evaluate the prognostic impact of RDW levels at AML diagnosis. Methods: A total of 294 newly diagnosed AML patients (median age 60.6, range 14.3-76.5 years), with available diagnostic RDW levels were retrospectively included in this analysis. All patients received a consolidation therapy with an allogeneic HSCT in curative intention between August 2007 and December 2020 at the University Medical Center Leipzig. The RDW was measured in all patients at AML diagnosis before the start of cytoreductive therapies. Results: RDW levels at diagnosis were highly variable (median 16.6%, range 12%-30.6%) and above the upper level of normal (>15%) in 73% of the analyzed AML patients. Patients with RDW levels above 15% did not have worse outcomes compared to patients with low diagnostic RDW levels. However, when the cohort was dichotomized according to a receiver operating characteristic (ROC)-based optimal cut-point (20.7%), patients with high RDW levels had a significantly higher non-relapse mortality (NRM), shorter overall survival and a trend for shorter event-free survival, while the risk of relapse or disease progression was similar in both groups. In multivariate analyses, the RDW remained an independent prognostic factor for higher NRM after adjustment for the body mass index at diagnosis. Patients with a higher RDW were more likely to harbor a secondary AML, as well as to harbor secondary AML-associated gene mutations (i.e. JAK2, ASXL1, or spliceosome mutations, especially SRSF2). Conclusion: High RDW levels at diagnosis represent an independent risk marker for a higher mortality following allogeneic HSCT. When confirmed in prospective clinical trials, the RDW might help to personalize AML consolidation therapy including conditioning regimens before allogeneic HSCT.:1. Bibliographische Beschreibung 2. Abkürzungsverzeichnis 3. Einführung / Introduction 3.1. Acute Myeloid Leukemia 3.1.1. Definition 3.1.2. Epidemiology and etiology 3.1.3. Clinical presentation 3.1.4. Diagnosis of AML 3.1.4.1. Morphology 3.1.4.2. Immunophenotyping 3.1.4.3. Cytogenetic and molecular analyses 3.1.5. AML classification according to WHO classification 3.1.6. Prognostic factors in AML 3.1.6.1. Patient-related risk factors 3.1.6.2. Genetic risk factors 3.1.6.3. Measurable residual disease 3.1.7. Treatment of AML 3.1.7.1. Induction therapy in curative intention 3.1.7.2. Consolidation therapies 3.1.7.3. Palliative treatment approaches 3.1.7.4. New substances 3.2. Allogeneic HSCT 3.2.1. Principles of allogeneic HSCT 3.2.2. Conditioning regimens 3.3. Red cell distribution width 4. Aufgabenstellung / Objectives 5. Materialien und Methoden / Materials and Methods 5.1. Patients and treatments 5.1.1. Treatment protocols 5.1.2. Allogeneic HSCT and immunosuppression 5.1.3. Assessment of GvHD 5.2. Disease characterization 5.2.1. Evaluation at AML diagnosis 5.2.1.1. Morphology 5.2.1.2. Flow cytometry 5.2.1.3. Genetic analyses 5.2.1.4. Evaluation of RDW levels 5.2.2. Evaluation at HSCT 5.2.2.1. Definition of remission status at HSCT 5.2.2.2. Evaluation of measurable residual disease at HSCT 5.3. Statistical Analyses 5.3.1. Associations 5.3.2. Clinical endpoints 5.3.3. Definition of an optimal cut-point for RDW levels 5.3.4. Multivariate analyses 6. Ergebnisse / Results 6.1. Overall outcomes of the patient cohort 6.2. RDW levels at AML diagnosis regarded as continous parameter 6.3. The role of RDW levels at diagnosis as a predictor for outcomes after allogeneic HSCT 6.4. Associations of RDW levels at diagnosis 7. Diskussion / Discussion 8. Zusammenfassung / Summary 9. Literaturverzeichnis / References 10. Erklärung über die eigenständige Abfassung der Arbeit 11. Curriculum Vitae 12. Komplette Publikationsliste (Peer-reviewed) 13. Danksagung

Construction of tunnels and small- to medium-span bridges is a $12 billion per year industry in the United States, with a significant portion going into buried arch structures. Notwithstanding such expenditure, modern arch design and construction, in many cases, is highly conservative. This is because the closed-form solutions used by most designers today do not correctly account for soil-structure interaction. In fact, soil-structure interaction makes a closed form solution impossible. With the advent of high power computers in recent years, some designers have turned to finite element (FE)modeling as the main vehicle of analysis. Such numerical procedures provide an accurate approximation of physical behavior. Practices using FE analysis for buried arch design almost exclusively use two-dimensional models because they are faster to set up and analyze than three-dimensional models and cost substantially less. However, 2-D models fail to account for the stiffness of the structure and spread of discrete loads in the third-dimension. Both the 1996 and 1998 AASHTO-LRFD Bridge Design Specifications address this problem, providing methods of load reduction. Much of the current reduction, however, is based on research done on concrete bridge decks, and does not account for continuous elastic support or the geometry of the structure. This results in a conservative analysis at low fill covers (<10') and/or increasing spans (>20’). This research provides a method to rectify the discrepancy that arises in discrete loading of 2-D FE models of semi-flexible buried concrete arch bridge, culvert, and tunnel systems due to the plane-strain assumption. Rectification is accomplished by providing a correlation between the deflection of a beam-on-elastic-foundation analysis and a distribution length by which the load in 2-D analysis is reduced. Distribution lengths are derived using bending energy ratios. The correlation considers structural geometry, overburden height, and base soil stiffness. Reduction of the 2-D design load by the proposed distribution length results in shear forces and bending moments nearly equivalent to those obtained from 3-D analysis in the plane of discrete load application transverse to the structure. Less conservative results are also obtained for axial forces. These results are intended for use on structures that are four times the span in length, or longer.

Bridge edge beam system is an increasing concern in Sweden. Because it is the mostvisible part of the structure which is subjected to harsh weather. The edge beamcontributes to the stiffness of overhang slab and helps to distribute the concentratedload. The design of edge beam is not only affected by the structural members, but it isalso affected by non-structural members.The aim of the thesis is to investigate the influence of edge beam on the structuralbehavior of reinforced concrete overhang slab. A three-dimensional (3D) non-linearfinite element model is developed by using the commercial software ABAQUS version6.1.14. The load displacement curves and failure modes were observed. The bendingmoment and shear capacity of the cantilever slab is studied.The validated model from non-linear analysis of reinforced concrete slab gives morestiffer result and leads to the high value of load capacity when comparing with theexperimental test. The presence of the edge beam in the overhang slab of length 2.4 mslightly increases the load capacity and shows ductile behavior due to the self-weightof the edge beam. The non-linear FE-analysis of overhang slab of length 10 m leads tomuch higher load capacity and gives stiffer response as compare to the overhang slabof 2.4 m. The presence of the edge beam in the overhang slab of length 10 m giveshigher load capacity and shows stiffer response when comparing with the overhangslab of length 10 m. This might be due to the self-weight of the edge beam and theoverhang slab is restrained at the right side of the slab.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Ischemic heart diseases stands out among the diseases that affect the cardiovascular system due to its high prevalence and its impact on mortality in the general population. Ischemic heart disease is the leading worldwide cause of mortality. Fenomenum that also happens in the Americas and Brazil. The term acute coronary syndrome (ACS) is used to describe a heterogeneous spectrum of clinical conditions associated with acute myocardial ischemia, including unstable angina and acute myocardial infarction (AMI). The plurality in its clinical presentation represents a diagnostic challenge for clinicians. Moreover, appropriate risk stratification is mandadatory in all patients with ACS. Some clinical tools such as physical examination, electrocardiographic observations and risk scores are extremely usefull to identify patients at high risk of unfavorable clinical outcomes. Scores of risk stratification, among those the Global Registry of Acute Coronary Events (GRACE), are widely used in the prognostic evaluation of patients with ACS.Some plasma biomarkers have also been used to improove risk stratification. The GRACE score is a fundamental part of the assessment of patients with ACS and may even prevent or minimize adverse consequences in these individuals. Nevertheless, the search for new potential prognostic parameters that could add information to these establised scores has been the subject of intense research. In this context, stands out the use of routine hematological tests , since the complete blood count is readily available for clinical use and has a good cost-benefit relationship. Recent studies have investigated the potential role of some of red cell indices, especially anemia and red cell distribution width (RDW), in the prognostic evaluation of patients with several cardiovascular conditions. The presence of anemia and elevated RDW in patients with ACS have been independently associated with increased risk of adverse events such as heart failure, recurrent ischemic events, and death. We have hipotezazed that the addition of the hemalological indices to the GRACE score would improve its ability to stratify patients.The main objective of this study was to investigate whether inclusion of anemia or RDW, assessed at admission, in the GRACE score model to predic in-hospital mortality, could improve the discrimination and calibration of these model, as well as risk stratification in patients with ACS. For this, a cohort study, including 109 patients with AMI was carried out. Cox regression models including the variables of the GRACE score and RDW or anemia were constructed. Measures of calibration and discrimination, and reclassification of patients were also calculated for the new models. The new models, either with the inclusion of anemia, or the addition of RDW showed adequate calibration and discrimination. Furthermore, the addition of these parameters to the original model allowed adequate reclassification of patients in different categories of risk. The red cell indices, anemia and RDW showed potential prognostic for use in risk assessment of patients with ACS, allowing the improvement of risk stratification performed through the GRACE score. / A cardiopatia isquêmica destaca-se entre as doenças que acometem o sistema cardiovascular, devido à sua alta prevalência e a seu impacto sobre a mortalidade na população em geral. As doenças isquêmicas do coração são a principal causa de mortalidade mundial, nas Américas e no Brasil. O termo SCA é usado para descrever um espectro heterogêneo de condições clínicas associadas com isquemia aguda do miocárdio, incluindo angina instável e infarto agudo do miocárdio (IAM). A diversidade na apresentação clínica de pacientes com esta patologia representa um desafio para os clínicos em termos de diagnóstico e de estratificação de risco apropriada. Algumas ferramentas clínicas como exame físico, observações eletrocardiográficas e escores de risco, são de extrema relevância na identificação de pacientes com alto risco de desfechos clínicos desfavoráveis. Além disso, alguns biomarcadores plasmáticos também vêm sendo utilizados com este propósito e a busca por novos parâmetros com potencial prognóstico tem sido alvo de intensas pesquisas. Neste contexto, destaca-se a utilização dos testes hematológicos de rotina na estratificação de risco, uma vez que o hemograma é um exame amplamente disponível para uso clínico e possui uma boa relação custo benefício. Estudos recentes tem investigado o potencial papel de alguns dos índices hematimétricos, especialmente anemia e amplitude de distribuição dos eritrócitos (RDW), na avaliação prognóstica de pacientes apresentando diversas condições cardiovasculares. A presença de anemia, bem como valores elevados de RDW em pacientes com SCA tem sido independentemente associados com maior risco de eventos adversos como mortalidade, desenvolvimento de insuficiência cardíaca e ocorrência de eventos isquêmicos recorrentes. Os escores de estratificação de risco, principalmente o Global Registry of Acute Coronary Events (GRACE), são amplamente utilizados na avaliação prognóstica de pacientes com SCA. No entanto, os modelos disponíveis atualmente não incluem os índices hematimétricos na determinação do risco do paciente. Considerando que a estratificação de risco é parte fundamental da avaliação de pacientes com SCA, podendo evitar ou mesmo minimizar consequências adversas nestes indivíduos, o principal objetivo deste estudo foi investigar se a inclusão de anemia ou RDW, avaliados na admissão hospitalar, ao escore GRACE para a predição de mortalidade durante o período de internação hospitalar, podem melhorar a calibração e discriminação do modelo, bem como a estratificação de risco em pacientes com SCA. Para isso, um estudo de coorte, incluindo 109 pacientes com IAM, foi realizado. Modelos de regressão de Cox incluindo as variáveis do escore GRACE e o RDW ou a anemia foram construídos. Medidas de calibração e discriminação também foram calculadas, bem como o percentual de reclassificação dos pacientes para os novos modelos propostos. Os novos modelos, tanto com a inclusão de anemia, quanto com a adição de RDW, apresentaram adequada calibração e discriminação. Além disso, a adição destes parâmetros ao modelo original permitiu uma adequada reclassificação dos pacientes em diferentes categorias de risco. Os índices hematimétricos, anemia e RDW, demonstraram potencial prognóstico para utilização na avaliação de risco de pacientes com SCA, permitindo o aprimoramento da estratificação de risco realizada através do escore GRACE.

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