No description available.

No description available.

The most common cause of death in patients with sepsis/septic shock is deterioration of the function of multiple organs, termed multiple organ dysfunction syndrome. Although our understanding of mechanisms involved in the pathophysiology of sepsis-induced tissue damage has improved substantially, therapy of these syndromes still remains largely supportive. The hallmark of sepsis is an overwhelming systemic production of both pro- and anti-inflammatory mediators leading to generalized endothelial and epithelial damage, microcirculatory-mitochondrial distress, altered endocrine and coagulation homeostasis and cellular immune hyporesponsiveness. Therefore, the hypothesis that modulation of this excessive immunological and biological response to infection might improve patient outcome appears reasonable. Hemoelimination techniques represent biologically plausible way to provide non-specific removal of soluble pro- and anti-inflammatory mediators, although the concept of blood purification in sepsis remains a matter of considerable debate. The aim of this thesis was to elucidate effects of 1) high volume hemofiltration (HVHF) and 2) coupled plasma filtration adsorption (CPFA) in a long-term, hyperdynamic porcine septic shock model, which fulfils the criteria for human sepsis. We hypothesized that both HVHF and...

The most common cause of death in patients with sepsis/septic shock is deterioration of the function of multiple organs, termed multiple organ dysfunction syndrome. Although our understanding of mechanisms involved in the pathophysiology of sepsis-induced tissue damage has improved substantially, therapy of these syndromes still remains largely supportive. The hallmark of sepsis is an overwhelming systemic production of both pro- and anti-inflammatory mediators leading to generalized endothelial and epithelial damage, microcirculatory-mitochondrial distress, altered endocrine and coagulation homeostasis and cellular immune hyporesponsiveness. Therefore, the hypothesis that modulation of this excessive immunological and biological response to infection might improve patient outcome appears reasonable. Hemoelimination techniques represent biologically plausible way to provide non-specific removal of soluble pro- and anti-inflammatory mediators, although the concept of blood purification in sepsis remains a matter of considerable debate. The aim of this thesis was to elucidate effects of 1) high volume hemofiltration (HVHF) and 2) coupled plasma filtration adsorption (CPFA) in a long-term, hyperdynamic porcine septic shock model, which fulfils the criteria for human sepsis. We hypothesized that both HVHF and...

Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ failure (MOF). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MOF are also not fully elucidated. As a result, successful therapies for trauma-related MOF are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through Toll-like receptor (TLR)-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. The first aim of this PhD thesis was to determine whether mtDNA released after trauma haemorrhage is sufficient for the development of MOF. Secondly, I then aimed to determine the extent of mtDNA release with varying degrees of tissue injury and haemorrhagic shock in a clinically relevant rodent model. My final aim was to determine whether neutralising mtDNA at a clinically relevant time point in vivo would reduce the severity of organ injury in this model.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

No description available.

Introduction: Trauma is the main cause of death in working-age adults in the UK. Multiple organ failure (MOF) is associated with a high proportion of late trauma deaths, and MOF survivors have poor long-term outcomes. Early prediction of patients at risk of MOF would assist treatment decisions and allow targeted interventions. Methods: A cohort of major trauma patients requiring intensive care unit (ICU) treatment at the John Radcliffe Hospital was identified. Data were obtained from the two national databases of the Trauma Audit Research Network and the Intensive Care National Audit and Research Centre, and from a local ICU database with hourly data recording. Literature review and questionnaire analysis of trauma clinicians identified candidate predictors of MOF, grouped into patient, injury, physiological, laboratory and management variables. MOF scoring systems were reviewed to determine the most appropriate for use in trauma patients. Prediction models of post-trauma MOF were developed using logistic regression at a range of times from 0 to 48 hours after injury. Models were internally validated using bootstrapping. Results: 517 adult trauma patients were identified from 2003-2011. Overall mortality was 14.9%, with 491 patients surviving more than 48 hours, and therefore being at risk of MOF development. For these 491 patients, MOF incidence depended on the definition, and ranged from 23% (Denver score) to 58% (SOFA score). MOF was associated with mortality, time to ICU admission, and length of ICU and hospital stay. MOF could be predicted with an accuracy of up to 81.3% at 2 hours post-injury, and 84.2% at 12 hours post-injury using small numbers of clinical variables. Age, head injury, abdominal injury, maximum heart rate and the need for vasopressors were strong predictors of all definitions of MOF. Conclusions: Post-trauma MOF can be predicted early after injury using combinations of clinical variables. Further validation of the identified variables on external populations would allow development of a clinical score to assist clinicians in trauma management.

Orientador: Desanka Dragosavac, Luis Alberto Magna / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T08:33:07Z (GMT). No. of bitstreams: 1 Antunes_Nilson.pdf: 1392711 bytes, checksum: 89e9cd241a2037104655c013c2724bfc (MD5) Previous issue date: 2009 / Resumo: Objetivo: Investigar a eficácia da ultrafiltração na remoção de mediadores inflamatórios liberados pela circulação extracorpórea e correlacionar ultrafiltração com alterações da função orgânica de acordo com o "Seqüential Organ Failure Assessment Score". Métodos: Quarenta pacientes foram incluídos e randomizados em dois grupos: "sem ultrafiltração" (n=20; Grupo I) e "ultrafiltração" (n=20; Grupo II). Complementos 3 e 4 ativados, interleucina 1beta, 6, 8 e fator de necrose tumoral alfa foram dosados antes da indução anestésica (T1), 5 minutos antes da circulação extracorpórea (T2), no líquido ultrafiltrado (T3), 30 minutos (T4), 6 (T5), 12 (T6), 24 (T7), 36 (T8) e 48 (T9) horas após término da circulação extracorpórea. "Sequential Organ Failure Assessment Score" foi avaliado nos tempos 1, 6 e 9. Significância estatística foi estabelecida com p = 0,05. Resultados: No líquido ultrafiltrado, apenas níveis de fator de necrose tumoral alfa foram detectados. Níveis de complemento 3 ativado, nos tempos 5 e 7, e complemento 4 ativado, nos tempos 5 e 6, foram significativamente elevados no grupo sem ultrafiltração, e níveis de interleucina 6 foram elevados no grupo ultrafiltrado, nos tempos 7 e 8. Interleucina 1beta, 8, fator de necrose tumoral alfa, e "Sequential Organ Failure Assessment Score" não tiveram diferenças significantes entre os grupos. Conclusões: Ultrafiltração retira significativamente fator de necrose tumoral alfa, mas isto não influencia nos níveis séricos desta citocina. Ultrafiltração com o tipo de filtro usado neste estudo não filtra outros mediadores inflamatórios estudados e não diminui a disfunção orgânica no pós-operatório. Deverá ser usada apenas para controle volêmico nos pacientes submetidos à circulação extracorpórea. / Abstract: Objective: To investigate the effectiveness of ultrafiltration in removing inflammatory mediators released by cardiopulmonary bypass and to correlate ultrafiltration with alterations in organic function according to the Sequential Organ Failure Assessment Score. Methods: Forty patients were included and randomized into two groups: "no ultrafiltration" (n=20; Group I) and "ultrafiltration" (n=20; Group II). Activated complement 3 and 4, interleukins 1beta, 6, 8 and tumor necrosis factor alfa were measured prior to anesthesia induction (Time 1), 5 minutes before cardiopulmonary bypass (Time 2), in the ultrafiltrated fluid (Time 3), 30 minutes (Time 4), and 6 (Time 5), 12 (Time 6), 24 (Time 7), 36 (Time 8) and 48 (Time 9) hours following cardiopulmonary bypass. Sequential Organ Failure Assessment Score was evaluated at Time 1, 6 and 9. Statistical significance was established at p = 0.05. Results: In the ultrafiltrated fluid, only tumor necrosis factor alfa levels were detected. Levels of activated complement 3 at Times 5 and 7 and activated complement 4 at Times 5 and 6 were significantly higher in the unfiltered Group, and levels of interleukin 6 were higher in the filtered Group at Times 7 and 8. Interleukins 1beta, 8, tumor necrosis factor alfa, and the Sequential Organ Failure Assessment score were not significantly different between the groups. Conclusions: Ultrafiltration significantly filtered tumor necrosis factor alfa but did not influences serum levels of this cytokine. Ultrafiltration with the type of filter used in this study had no effect in organic dysfunction and should be used only for volemic control in patients undergoing cardiopulmonary bypass. / Universidade Estadual de Campi / Pesquisa Experimental / Doutor em Cirurgia