Univ., Diss., 2006--Giessen

Ο ρόλος της φαγοκυτταρικής ικανότητας των μονοκυττάρων και των πολυμορφοπυρήνων στην σήψη δεν έχει μελετηθεί επαρκώς. Η παρούσα έρευνα είχε ως σκοπό να εκτιμήσει την επίδραση της φαγοκυτταρικής δραστηριότητας των μακροφάγων στην τελική έκβαση ασθενών με βαριά σήψη. 31 ασθενείς και 30 υγιή άτομα πήραν μέρος στην μελέτη. Η φαγοκυττάρωση των πολυμορφοπυρήνων και των μονοκυττάρων εκτιμήθηκε τις πρώτες 24 ώρες μετά την εισαγωγή του ασθενούς ενώ τα αποτελέσματα συσχετίσθηκαν με την έκφραση του CD64 στα πολυμορφοπύρηνα και στα μονοκύτταρα, την έκφραση του CD14 στα μονοκύτταρα, το SAPSII score και την επιβίωση των ασθενών. Η ελαττωμένη φαγοκυττάρωση των ουδετεροφίλων τις πρώτες 24 ώρες μετά την εισαγωγή ήταν αρνητικός προγνωστικός δείκτης για την επιβίωση. Η αυξημένη έκφραση τoυ CD64 τόσο στα PMN όσο και στα μονοκύτταρα επηρέασε θετικά την πρόγνωση των ασθενών. Σε πολυπαραγοντική ανάλυση η φαγοκυτταρική δραστηριότητα των πολυμορφοπυρήνων ήταν ο μοναδικός ανεξάρτητος προγνωστικός παράγοντας για τη επιβίωση. Ασθενείς με φαγοκυτταρική δραστηριότητα PMN<37% παρουσίασαν μικρότερη έκφραση του CD64 στα πολυμορφοπύρηνα και στα μονοκύτταρα και κακή πρόγνωση ενώ ασθενείς με φαγοκυτταρική δραστηριότητα PMN>37% παρουσίασαν μεγαλύτερη έκφραση CD64 στα ουδετερόφιλα και στα μονοκύτταρα και καλή πρόγνωση. Η ελαττωμένη φαγοκυτταρική ικανότητα των ουδετεροφίλων πιθανά αντιπροσωπεύει μία κατάσταση ελαττωμένης δραστηριότητας παρόμοια με εκείνη των μονοκυττάρων κατα την διάρκεια του CARS (Compensatory Anti-inflammatory response syndrome, σύνδρομο αντισταθμιστικής αντιφλεγμονώδους απάντησης). Η χημειοτακτική δραστηριότητα των πολυμορφοπυρήνων στους επιβιώσαντες ασθενείς ήταν σημαντικά αυξημένη σε σχέση με τους ασθενείς που απεβίωσαν ενώ αντίθετα δεν παρουσιάσθηκε στατιστικά σημαντική διαφορά στην χημειοτακτική ικανότητα των ουδετεροφίλων ανάμεσα στην ημέρα της εισαγωγής και την ημέρα του εξιτηρίου. H χορήγηση του αυξητικού παράγοντα G-CSF στους ογκολογικούς ασθενείς με εμπύρετο ουδετεροπενία δεν επηρέασε την φαγοκυτταρική δραστηριότητα των πολυμορφοπυρήνων σε σημαντικό βαθμό. / The role of the effector function of monocytes and neutrophils in sepsis has been poorly investigated. The present study assessed the phagocytic activity of monocytes and neutrophils and evaluated its predictive significance in septic patients 31 patients with severe sepsis and 30 healthy individuals were enrolled in the study. The phagocytic activity of monocytes and neutrophils was evaluated and the results were correlated to the expression of CD64 on neutrophils and monocytes, CD14 antigen on monocytes, the SAPS score and the patients’ survival. The phagocytic activity of polymorphonuclears (PMN) in 24 hours after admission was decreased in all patients. Patients with PMN phagocytic activity <40% had lower expression of CD64 on monocytes and PMN and worse outcome while those with phagocytic activity>40% had higher expression of CD64 on monocytes and PMN and better outcome. In multivariate analysis the phagocytic activity of PMN was the only independent predictor factor for patients’ survival. The phagocytic activity of neutrophils in septic patients is a significant parameter of the final outcome. The upregulation of PMN CD64 expression is prerequisite for their increased phagocytic function but does not reflect it. The chemotactic functionof neutrophils was significantly increased in survivors compared to non survivors.In contrast, no statistical significance of chemotactic activity of PMNs was detected between the admission day and the day of discharge. The administration Of G-CSF in cancer patients with febrile neutropenia did not increase the phagocytic activity of neutrophils.

Orientador: Lígia Maria Suppo Souza Rugolo / Resumo: A sepse neonatal tardia é importante causa de morbidade e mortalidade em recém-nascidos prematuros. Os sinais e sintomas são inespecíficos, o que dificulta o diagnóstico. As citocinas são potentes mediadores inflamatórios que desempenham importante papel na patogênese da infecção. Níveis séricos aumentados de citocinas são observados durante infecções. A Interleucina 8 (IL-8) tem função de atrair e ativar neutrófilos, mantendo o processo inflamatório. O objetivo deste estudo foi determinar os níveis séricos e urinários da IL-8 em recém-nascidos prematuros com sepse tardia confirmada por culturas (sangue, urina ou líquor) ou associada com meningite, e avaliar se os níveis urinários de IL-8 podem ser utilizados como teste diagnóstico da sepse neonatal tardia. Amostras de sangue e urina foram coletadas de 36 RN prematuros com suspeita clínica de sepse tardia e os exames foram repetidos após 48 horas do início do estudo. Os valores séricos e urinários da IL-8 foram determinados pelo método de ELISA e a IL-8 urinária foi ajustada pelo valor da creatinina urinária. Dois grupos foram constituídos: Grupo séptico: 19 RN com sepse confirmada por culturas ou associada a meningite, idade gestacional (IG) de 31 ± 2,5 semanas, peso de nascimento (PN) de 1350 ± 420g, idade pós-natal (IPN) de 9,7 ± 5,3 dias e Grupo não infectado: 17 RN nos quais o diagnóstico de sepse foi excluído, IG 31 ± 2,1 sem, PN 1510 ± 380g, IPN 6,9 ± 4,1 dias. A mediana dos níveis séricos da IL-8 não diferiu estatisticamente entre os grupos séptico e não infectado (929 x 624 pg/ml; p=0,079) mas os níveis urinários (IL-8 ur/cr) foram significativamente maiores no grupo séptico (249 x 41,7; p<0,001). O ponto de corte ótimo da IL-8 sérica foi de 304 pg/ml com sensibilidade de 84% (IC 95%: 60 a 95%) e especificidade de 47% (IC 95%: 23 a 72%)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Late onset sepsis (LOS) is an important cause of morbidity and mortality in preterm infants. However, the diagnosis of LOS is difficult. Elevated serum levels of cytokines have been found during infections and this plays a critical role in the pathogenesis of infections. Interleukin 8 (IL-8) attracts and activates neutrophils which is crucial for the maintenance of the inflamatory process. The aim of this study was to determine serum and urine IL-8 levels in preterm infants with clinical LOS and positive culture (blood, urine ou cerebrospinal fluid) or meningitis and to evaluate if IL-8 levels can be a useful test for the diagnosis of LOS. Blood and urine were obtained from 36 premature babies with clinical signs of LOS and the collection of the samples were repeated after two days. Serum and urine IL-8 levels were determined by ELISA and the urine IL-8 concentration was corrected with the urine creatinine level. Nineteen preterm infants with sepsis (positive cultures or meningitis) - LOS Group: gestational age (GA) 31 ± 2.5wk, Birth Weight (BW) 1.35 ± 0.42 Kg, postnatal age(PNA) 9.7 ± 5.3 days and 17 noninfected - Control Group: GA 31 ± 2.1wk, BW 1.51 ± 0.38, PNA 6.9 ± 4.1 days, were studied. The medium serum IL-8 levels were not statistically different between groups (LOS vs Control, 929 x 624 pg/ml; p=0,079) but urine IL-8 levels were significantly higher in the LOS group when compared with the noninfected (249 x 41,7 p<0,001). The optimal cut-off point was 304pg/ml for serum IL8 with 84% sensitivity (95% CI: 60-95%) and 47% specificity (95% CI: 23-72%). The cut-off point for urine IL-8 was 89 with 100% sensitivity (95% CI: 82-100%) and 100% specificity (95%CI:81-100%). Two days after of clinical signs of LOS, urine IL-8 levels decreased in LOS group (p<0,001). The decrease in serum IL-8 levels in the LOS group was not statistically different (p=0,123)... (Complete abstract, click electronic address below) / Doutor

Bakgrund: Sepsis är ett allvarligt tillstånd som kan leda till svåra komplikationer och död. Tidig identifiering och hantering är därför nödvändigt. Sjuksköterskan har en viktig roll i att uppmärksamma förändringar. Syfte: Syftet med litteraturöversikten var att beskriva hur sjuksköterskan i sin roll kan identifiera sepsis och vad som kan bidra till att sepsis identifieras. Metod: Tio kvantitativa artiklar och en kvalitativ analyserades och sammanställdes till litteraturöversiktens resultat. Resultat: Sjuksköterskans roll vid kommunikation och samarbete med andra i ett vårdteam, liksom kunskap om sepsis kan ha betydelse för tidig identifiering av sepsis. Genom evidensbaserade riktlinjer, protokoll och utbildning kan identifiering effektiviseras. Diskussion: Genom att sjuksköterskan kommunicerar via SBAR, deltar i multidisciplinära team, använder olika instrument och riktlinjer, medverkar i utveckling av protokoll samt ökar sina kunskaper via utbildning effektiviseras identifiering av sepsis. Slutsats: Denna litteraturöversikt pekar på brister som kan ses i sjuksköterskans roll vid identifiering av sepsis samt förslag på åtgärder som kan förbättra dem. Vidare forskning bör fokusera på sjuksköterskans roll i kombination med sepsis, utvärdera sepsisteam, samarbete vid simulering, upplevelsen av instrument samt utbildningsprogram. / <p>Godkännande datum: 2018-03-26</p>

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...

Thesis (M.S.M.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / BACKGROUND: Atrial fibrillation (AF) that occurs during acute critical illnesses such as sepsis may have different risk factors than AF that occurs in the community setting. METHODS: We investigated associations between baseline electrocardiographic (ECG) parameters related to conduction, ischemia, and chamber size and new-onset AF that occurs in the setting of severe sepsis in a matched case-referent study. We matched 100 patients with new-onset AF during sepsis to 300 patients with similar age (plus or minus 5 years) who were hospitalized within Boston Medical Center intensive care units (ICU) between 2003-2009 with sepsis. Variables that were found to be significant (p<0.05) during conditional univariable logistic regression were entered into age, sex and race-adjusted conditional logistic regression in order to identify risk factors for new-onset AF during sepsis. RESULTS: Among 100 case and 300 referent patients with sepsis, the distribution of mean age was 69 +/-11 years vs. 71 +/- 11 years, sex was 42% female vs. 49% female, and race was 56% white and 33% black vs. 65% white and 21% black between cases and referents, respectively. Univariable analysis revealed that older age per year [OR 1.25 95% CI (1.07-1.46), p<0.01], longer PR interval per millisecond [168 +/- 43 ms vs. 157 +/- 30 ms; OR 1.01 95% CI (1.00-1.02), p=0.02], and presence of left bundle branch block (LBBB) [9 (9%) vs. 7 (2.3%); OR 4.42 95% CI (1.45-13.5), p<0.01] were significant risk factors among the new-AF cases. Our multivariable model found significant associations between new-onset AF during hospitalization and presence of prolonged PR interval per millisecond [OR 1.01 95% CI (1.00-1.02), p=0.04] and LBBB [OR 6.83 95% CI (1.68-27.8), p=0.01] on ICU admission ECG. CONCLUSION: Increased PR interval length and LBBB found on a 12-lead ECG upon ICU admission was associated with new-onset AF during hospitalization in the setting of sepsis. / 2031-01-01

INTRODUÇÃO: A sepse é uma resposta inflamatória sistêmica causada por infecção suspeita ou confirmada. As avaliações clínicas são essenciais para a sua detecção e tratamento precoce. Hemoculturas podem demorar até dois dias para produzir um resultado, e nem sempre são confiáveis. No entanto, estudos recentes sugeriram que a expressão de CD64 de neutrófilos pode ser uma alternativa sensível e específica para o diagnóstico de uma infecção sistêmica. OBJETIVO: Analisar a diferença de valores entre CD64 de indivíduos com síndrome de resposta inflamatória sistêmica (SIRS), e sepse suspeita ou confirmada, que satisfazem os critérios de diagnóstico para SIRS ao chegar na unidade de emergência. MÉTODO: Este foi um estudo de coorte prospectivo observacional. A amostra foi composta de 109 pacientes com idade de 18 anos ou mais, com critérios de SIRS na chegada ao serviço de emergência. Expressão CD64 foi medida no prazo de 6 horas de internação, e novamente após 48 h. RESULTADOS: A análise da curva ROC sugeriu que um corte de 1.45 dos níveis de CD64 poderia diagnosticar sepse com uma sensibilidade de 0,85, especificidade de 0,75, uma precisão de 82,08%, um valor preditivo positivo de 0,964, um valor preditivo negativo de 0,375 e uma razão de verossimilhança de 3,3381. A área sob a curva foi de 0,832. CONCLUSÃO: CD64 parece ser útil como biomarcador, sensível e específico para discriminar entre SRIS e sépsis. / INTRODUCTION: Sepsis is a systemic inflammatory response to suspected or confirmed infection. Clinical evaluations are essential for its early detection and treatment. Blood cultures may take as long as two days to yield a result, and are not always reliable. However, recent studies have suggested that neutrophil CD64 expression may be a sensitive and specific alternative for the diagnosis of systemic infection. OBJECTIVE: To analyze the difference in CD64 values between subjects with systemic inflammatory response syndrome (SIRS), suspected or confirmed sepsis, who meet diagnostic criteria for SIRS upon arriving at an emergency unit. METHOD: This was a prospective observational cohort study. The sample consisted of 109 patients aged 18 years with criteria for SIRS on arrival to Emergency department. CD64 expression was measured within 6 hours of hospital admission, and once again after 48 h. RESULTS: ROC curve analysis suggested that a cutoff of 1.45 for CD64 expression could diagnose sepsis with a sensitivity of 0.85, a specificity of 0.75, an accuracy of 82.08%, a positive predictive value of 0.964, a negative predictive value of 0.375 and a positive likelihood ratio of 3.3381. The area under the curve was 0.832. CONCLUSION: CD64 appears to be a useful, sensitive and specific biomarker in discriminating between SIRS and sepsis.

Bakgrund: Bacteriaemi eller sepsis är ett vanligt förekommande tillstånd som kännetecknas av ett snabbt och diffust insjuknande inom akuta verksamheter. Tillståndet kräver en snabb handläggning, vilket innebär tidig identifiering med en snabb insättning av behandling för att undvika det livshotande tillståndet som kan leda till en dödlig utgång. Detta kräver att vårdpersonalen tidigt ska kunna kartlägga och behandla patienter där det föreligger allvarliga infektioner som sepsis. Syftet: med studien är att belysa den kliniska presentationen hos patienter med svåra infektioner som här definieras som att patienten antingen fick slutdiagnosen sepsis eller uppvisade en positiv blododling i prehospital miljö i relation till utfall. Dessutom belyses ambulanspersonalens förmåga att upptäcka tillståndet redan prehospitalt i relation till utfall. Metod: En retroperspektiv registergranskning med en kvantitativ ansats. Utfall definieras som död inom de första 30 dagarna. Resultat: Totalt deltog 854 patienter i studien. Bland dem dog 20% under de första 30 dagarna. Insjuknandet föreföll ofta att vara ospecifikt. Av de patienter som dog inom 30 dagar var luftvägarna den vanligaste organpåverkan och bland dem som överlevde 30 dagar var infektion i urinvägar den vanligaste orsaken. Det förelåg ingen könsskillnad med avseende på prognos. Tid från larm till start av antibiotikabehandling var kortare bland dem som dog   De som dog var i genomsnitt äldre.  De patienter som dog hade också en lägre grad av vakenhet, ett lägre blodtryck, en lägre syresättning, och en lägre kroppstemperatur samt högre andningsfrekvens jämfört med de som överlevde.  Bara i ca 15% av fallen noterade ambulanspersonalen en misstanke om sepsis och en sådan misstanke var lika ovanligt i båda grupperna. Diskussion: Bland patienter med slutdiagnosen sepsis eller bakterieami så är risken att dö under de första 30 dagarna hög. Det föreligger redan i den prehospitala miljön påtagliga skillnader mellan de patienter som kommer att överleva och de som kommer att dö med avseende på patientkaraktäristik, etiologi och vitalparametrar. Denna kunskap kanske i framtiden skulle kunna utnyttjas på ett mera systematiskt sätt eventuellt med hjälp av ett datorstöd. Men andelen fall där ambulanspersonalen misstänker sepsis är alltjämt för låg. En ökad utbildning och förbättrade beslutsstöd kan möjligen förbättra denna siffra.

INTRODUÇÃO: A sepse é uma resposta inflamatória sistêmica causada por infecção suspeita ou confirmada. As avaliações clínicas são essenciais para a sua detecção e tratamento precoce. Hemoculturas podem demorar até dois dias para produzir um resultado, e nem sempre são confiáveis. No entanto, estudos recentes sugeriram que a expressão de CD64 de neutrófilos pode ser uma alternativa sensível e específica para o diagnóstico de uma infecção sistêmica. OBJETIVO: Analisar a diferença de valores entre CD64 de indivíduos com síndrome de resposta inflamatória sistêmica (SIRS), e sepse suspeita ou confirmada, que satisfazem os critérios de diagnóstico para SIRS ao chegar na unidade de emergência. MÉTODO: Este foi um estudo de coorte prospectivo observacional. A amostra foi composta de 109 pacientes com idade de 18 anos ou mais, com critérios de SIRS na chegada ao serviço de emergência. Expressão CD64 foi medida no prazo de 6 horas de internação, e novamente após 48 h. RESULTADOS: A análise da curva ROC sugeriu que um corte de 1.45 dos níveis de CD64 poderia diagnosticar sepse com uma sensibilidade de 0,85, especificidade de 0,75, uma precisão de 82,08%, um valor preditivo positivo de 0,964, um valor preditivo negativo de 0,375 e uma razão de verossimilhança de 3,3381. A área sob a curva foi de 0,832. CONCLUSÃO: CD64 parece ser útil como biomarcador, sensível e específico para discriminar entre SRIS e sépsis. / INTRODUCTION: Sepsis is a systemic inflammatory response to suspected or confirmed infection. Clinical evaluations are essential for its early detection and treatment. Blood cultures may take as long as two days to yield a result, and are not always reliable. However, recent studies have suggested that neutrophil CD64 expression may be a sensitive and specific alternative for the diagnosis of systemic infection. OBJECTIVE: To analyze the difference in CD64 values between subjects with systemic inflammatory response syndrome (SIRS), suspected or confirmed sepsis, who meet diagnostic criteria for SIRS upon arriving at an emergency unit. METHOD: This was a prospective observational cohort study. The sample consisted of 109 patients aged 18 years with criteria for SIRS on arrival to Emergency department. CD64 expression was measured within 6 hours of hospital admission, and once again after 48 h. RESULTS: ROC curve analysis suggested that a cutoff of 1.45 for CD64 expression could diagnose sepsis with a sensitivity of 0.85, a specificity of 0.75, an accuracy of 82.08%, a positive predictive value of 0.964, a negative predictive value of 0.375 and a positive likelihood ratio of 3.3381. The area under the curve was 0.832. CONCLUSION: CD64 appears to be a useful, sensitive and specific biomarker in discriminating between SIRS and sepsis.

INTRODUÇÃO: A sepse é uma resposta inflamatória sistêmica causada por infecção suspeita ou confirmada. As avaliações clínicas são essenciais para a sua detecção e tratamento precoce. Hemoculturas podem demorar até dois dias para produzir um resultado, e nem sempre são confiáveis. No entanto, estudos recentes sugeriram que a expressão de CD64 de neutrófilos pode ser uma alternativa sensível e específica para o diagnóstico de uma infecção sistêmica. OBJETIVO: Analisar a diferença de valores entre CD64 de indivíduos com síndrome de resposta inflamatória sistêmica (SIRS), e sepse suspeita ou confirmada, que satisfazem os critérios de diagnóstico para SIRS ao chegar na unidade de emergência. MÉTODO: Este foi um estudo de coorte prospectivo observacional. A amostra foi composta de 109 pacientes com idade de 18 anos ou mais, com critérios de SIRS na chegada ao serviço de emergência. Expressão CD64 foi medida no prazo de 6 horas de internação, e novamente após 48 h. RESULTADOS: A análise da curva ROC sugeriu que um corte de 1.45 dos níveis de CD64 poderia diagnosticar sepse com uma sensibilidade de 0,85, especificidade de 0,75, uma precisão de 82,08%, um valor preditivo positivo de 0,964, um valor preditivo negativo de 0,375 e uma razão de verossimilhança de 3,3381. A área sob a curva foi de 0,832. CONCLUSÃO: CD64 parece ser útil como biomarcador, sensível e específico para discriminar entre SRIS e sépsis. / INTRODUCTION: Sepsis is a systemic inflammatory response to suspected or confirmed infection. Clinical evaluations are essential for its early detection and treatment. Blood cultures may take as long as two days to yield a result, and are not always reliable. However, recent studies have suggested that neutrophil CD64 expression may be a sensitive and specific alternative for the diagnosis of systemic infection. OBJECTIVE: To analyze the difference in CD64 values between subjects with systemic inflammatory response syndrome (SIRS), suspected or confirmed sepsis, who meet diagnostic criteria for SIRS upon arriving at an emergency unit. METHOD: This was a prospective observational cohort study. The sample consisted of 109 patients aged 18 years with criteria for SIRS on arrival to Emergency department. CD64 expression was measured within 6 hours of hospital admission, and once again after 48 h. RESULTS: ROC curve analysis suggested that a cutoff of 1.45 for CD64 expression could diagnose sepsis with a sensitivity of 0.85, a specificity of 0.75, an accuracy of 82.08%, a positive predictive value of 0.964, a negative predictive value of 0.375 and a positive likelihood ratio of 3.3381. The area under the curve was 0.832. CONCLUSION: CD64 appears to be a useful, sensitive and specific biomarker in discriminating between SIRS and sepsis.