A neutropenia é um achado freqüente em recém-nascidos de mães com pré-eclampsia. Estudos avaliando a ativação leucocitária nestes recém-nascidos são escassos. No entanto, as principais citocinas pró-inflamatórias envolvidas são a IL-8 e o GRO-α. O objetivo deste estudo foi avaliar os níveis plasmáticos de IL-8 e GRO-α em recémnascidos prematuros de mães com pré-eclampsia. Metodologia: Foram incluídos recém-nascidos com idade gestacional menor de 36 semanas e peso de nascimento inferior a 2000 gramas, sendo divididos em dois grupos de acordo com a presença ou ausência de pré-eclampsia materna. Os critérios de exclusão foram: malformações congênitas, erro inato de metabolismo ou anormalidades cromossômicas, infecções do grupo STORCH, óbito na sala de parto e recém-nascidos nos quais as mães possuíam hipertensão crônica sem a presença de pré-eclampsia. Nas primeiras 48 horas de vida, no momento de coleta assistencial, uma pequena amostra adicional de sangue foi obtida para dosagem de IL-8 e GRO-α pelo método de enzimoimunoensaio. Foram usados os testes qui-quadrado, T student, Mann-Whitney, Kruskal-Wallis e regressão logística múltipla. Resultados: 119 recém-prematuros (64 sem pré-eclampsia e 55 com pré-eclampsia). Os grupos foram similares quanto ao peso de nascimento, idade gestacional, escore de Apgar no 5’minuto, sepse, doença de membrana hialina , ventilação mecânica, nutrição parenteral total, enterocolite necrosante, hemorragia periventricular. O grupo com préeclampsia apresentou mais neutropenia, foi mais PIG, parto cesariano e menos bolsa rota superior a 18 horas. Os níveis de IL-8 foram maiores no grupo sem pré-eclampsia materna [157.1 pg/ml (86.4-261.3) e 26.54 pg/ml (3.6-87.2) p<0.001 para não préeclampticos e pré-eclampticos, respectivamente]. Após análise por regressão múltipla apenas a ausência de pré-eclampsia foi associada com níveis elevados de IL-8. Conclusão: O prematuro de mãe com pré-eclampsia apresenta níveis reduzidos de IL-8, sugerindo que a ativação leucocitária possa estar prejudicada nestes recém-nascidos. / Neutropenia is frequent in newborn infants of preeclamptic mothers.Information on leukocyte activation in those newborns is scarce, but IL-8 and GRO- are the main proinflammatory cytokines involved. The aim was to study IL-8 and GRO- plasma levels in preterm newborn infants of preeclamptic mothers. Methods: Newborn infants with gestational age < 36 weeks and birth weight < 2000 grams were included and divided: non-preeclamptic and preeclamptic groups. Exclusion criteria: major congenital malformations, inborn errors of metabolism or chromosomal anomalies,STORCH infections, inborn preterm that died in the delivery room, and those whose mothers had chronic hypertension without preeclampsia. During the regular blood sample collection in the first 48 hours, a small amount was used for IL-8 and GRO- measurement by enzyme immunoassay. Chi-square, Student s t test, Mann Whitney test, Kruskal-Wallis and multiple logistic regression model were employed. Results: 119 preterm infants (64 non-preeclamptic and 55 preeclamptic). They were similar in birth weight, gestational age, Apgar scores at 5 minutes, sepsis, SDR, mechanical ventilation, TPN, NEC, intraventricular hemorrhage and death. The preeclamptic group had more neutropenia, SGA, C Section, and less rupture of membranes for > 18 hours. IL-8 was higher in the non-preeclamptic [157.1 pg/ml (86.4-261.3) e 26.54 pg/ml (3.6-87.2) p<0.001 non-preeclamptic and preeclamptic groups, respectively]. GRO-α was similar [229.5 pg/ml (116.6-321.3) and 185.5 pg/ml (63.9-306.7) p=0.236 in non-preeclamptic and preeclamptic groups, respectively]. After multiple regression analysis only absence of preeclampsia was associated with high IL-8 levels. Conclusions: Preterm newborn infants of preeclamptic mothers have a decreased plasma level of IL-8, suggesting that the leukocyte activation may be impaired in infants of preeclamptic mothers.

Introdução: Durante a década passada, todas as crianças com câncer submetidas à quimioterapia que apresentassem um episódio de neutropenia febril (NF) eram hospitalizadas e manejadas com antibioticoterapia endovenosa de largo espectro, independente de sua condição clínica. Neste estudo, os autores comparam o uso de antibioticoterapia endovenosa versus a oral. Pacientes e Métodos: Foram selecionadas todas as crianças com idade inferior a 18 anos, classificadas como baixo risco para complicações e neutropênicas. O estudo ocorreu entre 2002 a 2005, na Unidade de Oncologia Pediátrica do Hospital de Clínicas de Porto Alegre. Os pacientes, divididos em grupo A e grupo B, eram randomizados a receberem terapia oral ou endovenosa. O tratamento utilizado para o grupo A foi ciprofloxacina e amoxicilinaclavulanato via oral e placebo endovenoso e para o grupo B, cefepime e placebo oral. Resultados: Foram selecionados 91 episódios consecutivos de NF em 58 crianças. Para os pacientes do grupo A, a taxa de falência foi de 51,2%, e a média de tempo de hospitalização foi de 8 dias (variação de 2-10). Para os pacientes tratados com antibioticoterapia endovenosa, a taxa de falência foi de 45,8%, e a média de tempo de hospitalização foi de 7 dias (variação de 3-10). Discussão: Neste estudo não houve diferenças entre o grupo oral versus a terapia endovenosa. Estudos randomizados com maior número de pacientes são necessários antes de padronizar a terapêutica oral como tratamento para esta população de pacientes. / Introduction: In the past decade nearly all children with cancer who suffered an episode of febrile neutropenia (FN) were hospitalized and managed with broad spectrum intravenous antimicrobials irrespective of their clinical condition. As the optimal therapy for FN cancer patients is not entirely known the authors compared the efficacy of an oral regimen with intravenous cefepime. Patients and Methods: Patients younger than 18 years of age and classified as low risk for complication and FN were selected from 2002 to 2005 at the Pediatric Oncology Unit of Hospital de Clinicas de Porto Alegre, Brazil. Patients were randomly assigned to receive oral or intravenous therapy. Empirical antimicrobial treatment used for group A was oral ciprofloxacin plus amoxicillin-clavulanate and intravenous placebo and group B was cefepime and oral placebo. Results: A total of 91 consecutive episodes of FN occurring in 58 children were included in this study. For patients treated with ciprofloxacin and amoxicillin+clavulanate the treatment failure rate was 51.2%. The median of length of stay was 8 days (range 2-10 days). For patients treated with cefepime the treatment failure rate was 45.8%. Of the 26 successful treatment episodes, the length of hospitalization was 7 days (range 3-10 days). Discussion: There was no difference in outcome in oral versus intravenous therapy. It is necessary larger prospective randomized multinstitutional trials will be required before oral empirical therapy administered on a patient basis should be considered the new standard of treatment for low risk patients.

Orientador: Sandra Helena Alves Bonon / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-21T11:41:57Z (GMT). No. of bitstreams: 1 Catalan_DanielThome_M.pdf: 2829035 bytes, checksum: 10145f8b164a7e70fc037a905f6026f6 (MD5) Previous issue date: 2012 / Resumo: Pacientes com doenças oncológicas possuem grandes períodos de neutropenia grave e são susceptíveis a complicações infecciosas. O tratamento com drogas quimioterápicas, radioterapia e em alguns casos cirurgia promovem depleção do sistema imunológico e exposição a microrganismos durante o processo cirúrgico. Durante o período de tratamento e em média até um ano após o término de terapia os episódios de febre são freqüentes e na maioria dos casos o agente etiológico não é conhecido. O tratamento faz-se então com administração de antibióticos de grande espectro, com a finalidade de realizar o tratamento empírico para vários tipos de microrganismos e a febre é chamada como febre de origem desconhecida. Através dos meios convencionais de diagnóstico uma pequena porcentagem de agentes etiológicos é identificada, e em muitos estudos não ultrapassa 25% dos episódios de febre. As hemoculturas normalmente são negativas e o tempo do diagnostico é prolongado. Dada a urgência nos cuidados com os pacientes oncológicos pediátricos a busca por um diagnóstico rápido com alta sensibilidade e especificidade se faz necessário. O objetivo deste estudo foi identificar a infecção ativa causada pelos herpesvírus (EBV, CMVH, HHV-6 e HHV-7) em pacientes oncológicos pediátricos com episódios de febre através das técnicas de Antigenemia para o CMV e N-PCR para o EBV, CMVH, HHV-6 e HHV- 7. Foram coletadas 169 amostras de soro para realização da N-PCR e 100 amostras de sangue total para realização do teste de antigenemia provenientes de 62 pacientes. Infecção ativa pelo Epstein-Barr vírus detectada pela N-PCR no soro ocorreu em 3/169 amostras (1,8%) em 3/62 pacientes diferentes (4,8%). Infecção ativa pelo CMVH foi detectada pela N-PCR em 16/169 amostras (9,5%) e em 12/62 (19,4%) pacientes; N-PCR no soro para detectar infecção ativa pelo HHV-6 ocorreu em 27/169 amostras (16,0%) e destas, 23/62 pacientes (37,1 %) foram acometidos. Infecção ativa causada pelo HHV-7 detectada pela N-PCR no soro ocorreu em 24/169 (14,8%) das amostras coletadas e em 18/62 (29,0%) pacientes. Para o teste de antigenemia para CMVH foram encontrados 5/100 (5,0%) de positividade nas amostras testadas e em 5/62 (8,1%) dos pacientes. Esses resultados mostram que a infecção ativa causada por pelo menos um dos herpesvírus EBV, CMV, HHV-6 e HHV-7 é frequente nessa população representando em nosso estudo 71/169 (42,0%) dos casos de febre e ocorreu em 62 pacientes portadores de neoplasia. Estudos futuros serão necessários com a inclusão de outros microrganismos para avaliar a etiologia da febre nos pacientes oncológicos pediátricos, assim como a introdução de novas técnicas de biologia molecular como a PCR quantitativa em tempo real / Abstract: Patients with infiltration cancer cells in bone marrow, solids tumors and treatment with chemotherapy promote high depletion of immune system activity. Most episodes with febrile neutropenia are treated with empiric broad-spectrum antibacterial therapy without identifying the site of infection or agent, such as fever unknown origin (FUO). Through the conventional diagnostic methods a small number of etiologic agents are identified, blood cultures and urine culture are usually negative and time-consuming to identify the source of infection for the clinic usually is difficult, nevertheless only identify bacteria and fungi. They are identified and confirmed by culture in only 25-30% of the cases, in other 15-25% of patients with fever bacterial or fungi infections are suspected on clinical findings and approximately 50% of cases are classified and treated as FUO. Given the urgency of care to cancer patients and fever need rapid diagnosis of infections in these patients, the search for new laboratory tests in order to promote high accuracy in identification of pathogens in these patients is important. The aim of this study is identify active infections caused by herpesvirus EBV, CMV, HHV-6 and HHV-7 in episodes of fever of pediatric oncology patients. 169 samples of whole blood and serum collected from patients with episodes of fever were analyzed using N-PCR methods and cytomegalovirus was analyzed by antigenemia and N-PCR. Active infection caused by Epstein-Barr virus occurred in 3/169 (1,8%)of samples and 3/62 (4,8%) of the patient; cytomegalovirus 16/169 (9,5%) of samples and 12/62 (19,4%) of the patient; HHV-6 27/169 (16,0%) of templates and 23/62 (37,1%) of the patient; HHV-7 24/169 (14,8%) of sample and 18/62 (29,1%) of the patient. This results shows that active infections caused by EBV, CMV, HHV-6 and HHV-7 are frequent in children receiving cancer treatment, representing high prevalence this cases of fever, with or without neutropenia. New assay are need with real time PCR for to better the diagnostic of the fever episodes / Mestrado / Clinica Medica / Mestre em Clinica Medica

Thesis (M.Med. (Paediatrics and Child Health)) -- University of Limpopo, 2022 / BACKGROUND Febrile neutropenia is a medical emergency that complicates the clinical course and treatment of both hematological and solid malignancies, potentially worsening the overall outcome and increasing the financial burden. The epidemiology of pathogens is varied, and determines the selection of empiric antibiotic therapy for febrile neutropenia. Empirically piperacillin/tazobactam plus amikacin has been recommended as the most suitable antibiotic for management of febrile neutropenia. There is a lack of local studies to provide advice for antibiotic choice in our setting. OBJECTIVE To identify causative organisms of infection and antibiotic susceptibility patterns in childhood cancer patients with chemotherapy related febrile neutropenia in Pietersburg Hospital Oncology Ward Limpopo Province. METHODS This is a retrospective cross-sectional study that reviewed all the febrile neutropenic episodes in children with cancer and with a positive blood culture during the febrile neutropenia episode. Data collected included patient demographics (date of birth, sex, date of diagnosis) diagnosis, organisms cultured and the antibiotic sensitivity profile. RESULTS There were 152 records of positive blood cultures identified of 348 episodes of febrile neutropenia for 413 patients. The median age of study population is 6years (mean age of 6.8years; range 3 to 11years) with male predominance at (61.2%). The most common cancer diagnosis was Acute Lymphoblastic Leukemia (ALL) (33.6%) followed by Nephroblastoma (15.8%), Acute myeloid leukemia (11.2%), Non- Hodgkin’s lymphoma (9.9%), Hodgkin’s lymphoma (5.9%) and other cancers (15.3%). The majority of causative organisms were gram-positive bacteria (45%) followed by gram-negative bacteria (32.4%) and fungi (6.1%). Gram-positive organisms were statistically significant pathogens causing bacteraemia more often in neutropenic patients than gram-negative organisms with a p value=0.016. The majority (n=102; 67.10%) were sensitive organisms with the minority being multidrug resistant organisms (n=23; 15.1%) and 17.8% were contaminants n=27. The most common gram-positive pathogens were Coagulase negative staphylococcus n=37; (21.6%). The most common multidrug resistant organisms were Klebsiella pneumoniae CRE (10.7 %;), followed by Enterococcus faecium VRE (1.9%), Klebsiella oxytoca CRE (1.3%), Enterococcus faecalis VRE (0.6%), and Staphylococcus aureus MRSA (0.6%). No multidrug resistant fungal organisms were cultured. The majority of organisms were sensitive to the first line empiric therapy piperacillin/tazobactam plus Amikacin (67.10%). Thirty patients died during these febrile neutropenic episodes and case fatality rate was 8.6%. CONCLUSION This study confirmed that the causative bacteria of febrile neutropenia in this study were susceptible to the first line empiric therapy piperacillin/tazobactam plus amikacin, and this regimen is therefore appropriate for this paediatric oncology unit.

Submitted by Fabiana Gonçalves Pinto (benf@ndc.uff.br) on 2017-08-28T20:29:28Z No. of bitstreams: 1 Elizabeth Maria Oliveira da Silva.pdf: 2307471 bytes, checksum: 8d4691afbac0bcd5899bff0e397c4b96 (MD5) / Made available in DSpace on 2017-08-28T20:29:28Z (GMT). No. of bitstreams: 1 Elizabeth Maria Oliveira da Silva.pdf: 2307471 bytes, checksum: 8d4691afbac0bcd5899bff0e397c4b96 (MD5) Previous issue date: 2016 / Mestrado Profissional em Enfermagem Assistencial / Problema: Atualmente o câncer infantil representa a segunda causa de morte na faixa etária de 5 a 19 anos, ultrapassado apenas pelos óbitos provocados por causas externas. E, a partir do diagnóstico, traça-se uma das propostas de tratamento, a terapêutica com os agentes antineoplásicos, conhecidos como quimioterápicos, os quais são responsáveis pelo longo período de internação, tendo em vista que um dos efeitos adversos desta terapêutica com maior incidência é a neutropenia pós-quimioterapia. Tal condição representada pela contagem de neutrófilos inferior a 1500/m3 torna necessário o uso de moduladores de resposta muitas vezes em domicílio. Objetivo: Este estudo tem como objetivo construir uma ação educativa durante a utilização em domicílio do fator estimulador de colônias granulocíticas (G-CSF), pelo paciente e/ou familiar, buscando conhecer o significado desta ação educativa a ser construída em conjunto com os familiares, considerando e respeitando o conhecimento e saber emanado por eles, em todo o processo holístico de saúde onde o indivíduo apresenta necessidades interligadas ao meio que o cerca. Método: É um estudo de natureza qualitativa, tipo descritivo com apropriação do método fenomenológico na percepção de Maurice Merleau Ponty, e a teoria transpessoal de Jean Watson e teve como cenário o centro de quimioterapia infantil do Instituto Nacional de Câncer, que é uma Instituição Pública Federal de referência na área oncológica, e obteve aprovação no CEP em 22/12/2015n° do CAAE-51715515.500005243 e no CEP da instituição coparticipante em 07/01/2016 n0 do CAAE-51715515.5.3001.5274. O estudo foi desenvolvido em conformidade com os princípios éticos estabelecidos na Resolução do Conselho Nacional de Saúde (CNS) 466/12. Resultado: A coleta de dados ocorreu no serviço de quimioterapia infantil por meio de entrevista com participação de dezoito familiares. As entrevistas foram transcritas na integra com apropriação do método de Giorgi e após analise a luz da fenomenologia da Percepção de Maurice Merleau-Ponty originou-se a formação de quatro categorias: Categoria 1-O impacto do diagnóstico de câncer na perspectiva do familiar; Categoria 2-O significado do câncer e tratamento na percepção do familiar; Categoria 3-A importância da espiritualidade na percepção do familiar da criança com câncer; 4-O significado do cuidado domiciliar na perspectiva do familiar. Considerações finais: Durante o decorrer deste estudo percorreu-se um caminho direcionado ao cuidado, tanto ao cuidador quanto do ser a ser cuidado com o objetivo de compreender e auxiliar os familiares no processo do cuidar a partir da percepção da experiência vivenciada por estes em um contexto familiar. Tais propósitos incluíram o respeito e valorização do conhecimento e das experiências desses familiares, incluindo suas crenças, cultura, e hábitos sociais. E, neste contexto é de extrema importância que o enfermeiro vivencie a experiência a partir da percepção do sujeito deste estudo, considerando os conceitos humanísticos, visando almejar uma assistência cada vez mais qualificada e de excelência, o que propiciou a construção de uma tecnologia educacional (cartilha educativa), no que se refere ao uso em domicilio do fator estimulador de crescimento de colônias de granulócitos / Problem: Currently, childhood cancer represents the second cause of death in the age group of 5 to 19 years, surpassed only by deaths caused by external causes. From the diagnosis, one of the treatment proposals is the treatment with antineoplastic agents, known as chemotherapeutic agents, which are responsible for the long period of hospitalization, considering that neutropenia is one of the adverse effects of this therapy with a higher incidence after chemotherapy. That condition, represented by the neutrophil count below 1500 / m3 makes it necessary to use response modulators often at home. Objective: This study aimed to construct an educational action during the use of the granulocytic colony-stimulating factor (G-CSF), by the patient and / or family member at home. It seeks to know the meaning of this educational action built together with the family, considering and respecting the knowledge and knowledge emanated by them, throughout the holistic process of health where the individual present needs interconnected to the environment that surrounds him. Method: It is a descriptive qualitative study, based on the phenomenological method from the perspective of Maurice Merleau Ponty, and the transpersonal theory of Jean Watson. It had as setting the child chemotherapy center of the National Cancer Institute, which is a public federal hospital, specialized in oncology area, and obtained approval in the CEP on 12/22/2015 under protocol number CAAE-51715515.500005243 and in the CEP of the participating Institution on 07/01/2016 under protocol number CAAE-51715515.5.3001.5274. The study was developed in conformity with the ethical principles set out in National Health Council (CNS) Resolution No.466/12. Results: Data collection took place in the infant chemotherapy service through an interview with the participation of eighteen relatives. We transcribed the interviews in full, with appropriation of the Giorgi method, followed by analysis under the perspective of the phenomenology of Perception by Maurice Merleau Ponty. Then, four categories originated category 1. The impact of the cancer diagnosis from the family perspective; category; 2. The meaning of the cancer and treatment under the perception of the family member; category 3. The importance of the spirituality under the perception of the family member of the child with cancer; -the meaning of home care from the perspective of the family member. Final Considerations. During the development of this study, we went through a path directed to care that reached both the caregiver and the being to be cared for with the objective of understanding and helping the family in the care process from the perception of experiences lived by them in a family context. Such purposes included the respect and valorization of the knowledge and experiences of these relatives, including their beliefs, culture, and social habits. And in this context, it is extremely important that nurses live the experience from the perception of the subject of this study, considering the humanistic concepts, aiming for an increasingly qualified and excellent assistance, which has enabled the construction process of an educational technology (educational leaflet) as regards the use at home of granulocytes colony stimulating factor

This article reports the findings of a grounded theory study of the processes involved in adherence and treatment seeking delay for febrile neutropenia in chemotherapy patients. Interviews were conducted with 12 patients. Six theoretical constructs were generated, namely ‘Recall of Treatment Advice’, ‘Impact of Emotions’, ‘Influence of Social Networks’, ‘Symptom Monitoring Behaviour’, ‘Symptom Interpretation’, and ‘Preparation and Journey Time’. A model was developed to reflect the complex interplay between these theoretical constructs. Data extracts are presented to illustrate the grounding of the model in patients’ accounts, and the model is discussed with reference to previous theory and research.

MARCO TEÓRICO A neutropenia é freqüente nos pacientes submetidos a quimioterapia e predispõe a um aumento na incidência de episódios infecciosos. A duração e intensidade do período de neutropenia estão diretamente relacionados à intensidade da quimioterapia administrada. A disponibilidade dos fatores de crescimento hematopoiéticos da linhagem mielóide, G-CSF e GM-CSF, constituíram-se em nova abordagem para reduzir o período de neutropenia e, presumivelmente, as complicações infecciosas. Não há consenso sobre a real utilidade do emprego de fatores de crescimento como terapia ad.iuvante em pacientes com leucemias agudas. Ensaios clínicos envolvendo leucemias agudas recaídas ou refratárias são raros e mostraram resultados similares aos obtidos nas leucemias agudas "de novo", ou seja, redução no período de neutropenia sem repercussão na taxa de óbito ou remissão. OBJETIVOS Principal: avaliar o efeito dos fa tores de crescimento sobre a mortalidade hospitalar dos portadores de leucemias agudas recaídas ou refratárias submetidos a quimioterapia ele alta- dose. Secundários: avaliar o impacto do uso destes fatores sobre o gasto com antibióticos, dias ele neutmpenia, dias de internação, dias de febre, incidência de infecções e taxa de remissão. CONCLUSÃO O emprego de fatores de crescimento, em pacientes com leucemia aguda recaída atendidos na clínica hematológica do Hospital de Clínicas de Porto Alegre, não modificou a taxa de mortalidade, a freqüência de remissão e outros parâmetros clínicos de interesse. / BACKGROUND Neutropenia is a common feature in patients treated with chemotherapy and is associated with an increased incidence of infections. The duration and intensity of neutropenia are mainly determin ated by the intensity of the chemotherapy regimen. Availability of recombinant myeloid growth factors (G-CSF and GM-CSF) brought up a new approach to reduce the duration of neutropenia and presumably, the incidence of infections. There i no consensus on the value of use of growth factors as adjuvant therapy in patients with acute leukemias. There is a few clinicai trials with patients 1..vith relapsed acute leukemias, and despire showing a reduction in the duration of neutropenia, they do not show reduction in the death or remission rates. ÜBJECTIVES Principal: to evaluate the effect of growth factors in the mortaliry rate of patients treatt!d with high-dose chemotherapy for relapsed acute leukemia. Secondary: to evaluate the effect of use of hematopoietic growth factors on the costs of antibiotic use, days of neutropenia, fever, lenght of hospitali:ation, and remission rares. CONCLUSION The use of hematopoietic growth factors in patients with relapsed acute leukenúa treated in the hematological clliúcs of the Hospital de Clfnicas de Porto Alegre did not modify the mortality rate, frequency of renússion and other clinicai parameters.

New approaches quantifying the effect of treatment are needed in oncology to improve the drug development process and to enable treatment optimization for existing therapies. This thesis focuses on the development of pharmacometric models for biomarkers, side effects and efficacy in order to identify predictors of clinical response in anti-cancer drug therapy. The variability in myelosuppression was characterized in six different cytotoxic anticancer treatments to evaluate a model-based dose individualization approach utilizing neutrophil counts as a biomarker. The estimated impact of inter-occasion variability was relatively low in relation to the inter-individual variability, indicating that myelosuppression is predictable from one treatment course to another. The approach may thereby be useful for dose optimization within an individual. To further study and to identify predictors for the severe side effect febrile neutropenia (FN), the relationship between the shape of the myelosuppression time-course and the probability of FN was characterized. Patients with a rapid decline in neutrophil counts and high drug sensitivity were identified to have a higher probability of developing FN compared with other patients who experience grade 4 neutropenia. Predictors of clinical response in patients receiving sunitinib for the treatment of gastro-intestinal stromal tumor (GIST) were identified by the development of an integrated modeling framework. Drug exposure, biomarkers, tumor dynamics, side effects and overall survival (OS) were linked in a unified structure, and univariate and multivariate exposure variables were tested for their predictive capacities. The soluble biomarker, sVEGFR-3 and tumor size at start of treatment were found to be promising predictors of overall survival, with decreased sVEGFR-3 levels and smaller baseline tumor size being predictive of longer OS. Also hypertension and neutropenia was identified as predictors of OS. The developed modeling framework may be useful to monitor clinical response, optimize dosing in sunitinib and to facilitate dose individualization.

This study was designed to evaluate the response of innate immunity to acute bacterial inflammation in terms of cytokines and other biomolecules concentration changes in the blood of investigated childhood oncology patients during the beginning of febrile neutropenia (FN) episode and to assess the relevance of these biomarkers for sepsis/bacteremia evaluation. This study was performed at Vilnius University Children Hospital and State Research Institute Centre for Innovative Medicine from 2009 to 2011. Serum samples were collected during 82 fever episodes in a total of 53 oncology patients. The study population consisted of pediatric oncology patients admitted to the hospital with the diagnosis of neutropenia and fever. According to microbiological and clinical findings, patients with episodes of FN were classified into 2 groups: 1) fever of unknown origin (FUO) group – patients with negative blood culture, absence of clinical signs of sepsis and clinically or microbiologically documented local infection, 2) septic/bacteremia (SB) group – patients with positive blood culture (documented Gram-positive or Gram-negative bacteremia) and/or clinically documented sepsis. We measured the levels of cytokines (IL-6, IL-8, IL-10), their receptors (sIL-2R) and other biomarkers (PCT, CRP, sHLA-G) for three consecutive days. We showed that on day 1 the most accurate biomarkers for bacteremia/sepsis discrimination were cytokines (IL-6, IL-10, IL-8), on day 2 – IL-8 and PCT. On day 1 the... [to full text] / Viena iš pagrindinių taikomos šiuolaikinės intensyvios chemoterapijos komplikacijų yra organizmo imuninės sistemos slopinimas ir su tuo susijusi neutropenija, kuri savo ruožtu sąlygoja padidėjusią riziką susirgti bakterinės kilmės infekcinėmis ligomis. Šio darbo tikslas buvo įvertinti ūmaus bakterinio uždegimo bei sepsio patogenezėje dalyvaujančių citokinų (IL-6, IL-8, IL-10), citokinų receptorių (sIL-2R), ūmios fazės baltymų bei kitų imuninio atsako komponentų (CRB, PCT, sHLA-G) tinkamumą bakterinio proceso ankstyvai diagnostikai tarp pacientų su febrline neutropenija (FN), šių biožymenų tinkamumą ir pritaikomumą kasdienėje klinikinėje praktikoje. Tiriamoji medžiaga surinkta 2009–2011 m. Vilniaus universiteto Vaikų ligoninės Onkohematologijos skyriuje. Į tyrimą buvo įtraukta 53 onkohematologinėmis ligomis sergantys vaikai su FN, kurie gydymo eigoje turėjo 82 karščiavimo epizodus. Nuo pirmos karščiavimo dienos tris dienas iš eilės buvo imami kraujo mėginiai bei nustatomos citokinų (IL-6, IL-8, IL-10), CRB, PCT, sHLA-G ir sIL-2R koncentracijos. Remiantis klinikinių bei mikrobiologinių tyrimų duomenimis, FN epizodai buvo suskirstyti į dvi grupes – neaiškios kilmės karščiavimo (NKK), į kurią buvo įtraukti pacientai be sepsio požymių bei su neigiamais mikrobiologiniais pasėliais ir bakteriemijos/sepsio (BS). BS grupę sudarė pacientai su teigiamais mikrobiologiniais pasėliais ir(ar) kliniškai diagnozuotu sepsiu. Mūsų atlikto tyrimo rezultatais bakteriemijos/sepsio vertinimui FN... [toliau žr. visą tekstą]

Viena iš pagrindinių taikomos šiuolaikinės intensyvios chemoterapijos komplikacijų yra organizmo imuninės sistemos slopinimas ir su tuo susijusi neutropenija, kuri savo ruožtu sąlygoja padidėjusią riziką susirgti bakterinės kilmės infekcinėmis ligomis. Šio darbo tikslas buvo įvertinti ūmaus bakterinio uždegimo bei sepsio patogenezėje dalyvaujančių citokinų (IL-6, IL-8, IL-10), citokinų receptorių (sIL-2R), ūmios fazės baltymų bei kitų imuninio atsako komponentų (CRB, PCT, sHLA-G) tinkamumą bakterinio proceso ankstyvai diagnostikai tarp pacientų su febrline neutropenija (FN), šių biožymenų tinkamumą ir pritaikomumą kasdienėje klinikinėje praktikoje. Tiriamoji medžiaga surinkta 2009–2011 m. Vilniaus universiteto Vaikų ligoninės Onkohematologijos skyriuje. Į tyrimą buvo įtraukta 53 onkohematologinėmis ligomis sergantys vaikai su FN, kurie gydymo eigoje turėjo 82 karščiavimo epizodus. Nuo pirmos karščiavimo dienos tris dienas iš eilės buvo imami kraujo mėginiai bei nustatomos citokinų (IL-6, IL-8, IL-10), CRB, PCT, sHLA-G ir sIL-2R koncentracijos. Remiantis klinikinių bei mikrobiologinių tyrimų duomenimis, FN epizodai buvo suskirstyti į dvi grupes – neaiškios kilmės karščiavimo (NKK), į kurią buvo įtraukti pacientai be sepsio požymių bei su neigiamais mikrobiologiniais pasėliais ir bakteriemijos/sepsio (BS). BS grupę sudarė pacientai su teigiamais mikrobiologiniais pasėliais ir(ar) kliniškai diagnozuotu sepsiu. Mūsų atlikto tyrimo rezultatais bakteriemijos/sepsio vertinimui FN... [toliau žr. visą tekstą] / This study was designed to evaluate the response of innate immunity to acute bacterial inflammation in terms of cytokines and other biomolecules concentration changes in the blood of investigated childhood oncology patients during the beginning of febrile neutropenia (FN) episode and to assess the relevance of these biomarkers for sepsis/bacteremia evaluation. This study was performed at Vilnius University Children Hospital and State Research Institute Centre for Innovative Medicine from 2009 to 2011. Serum samples were collected during 82 fever episodes in a total of 53 oncology patients. The study population consisted of pediatric oncology patients admitted to the hospital with the diagnosis of neutropenia and fever. According to microbiological and clinical findings, patients with episodes of FN were classified into 2 groups: 1) fever of unknown origin (FUO) group – patients with negative blood culture, absence of clinical signs of sepsis and clinically or microbiologically documented local infection, 2) septic/bacteremia (SB) group – patients with positive blood culture (documented Gram-positive or Gram-negative bacteremia) and/or clinically documented sepsis. We measured the levels of cytokines (IL-6, IL-8, IL-10), their receptors (sIL-2R) and other biomarkers (PCT, CRP, sHLA-G) for three consecutive days. We showed that on day 1 the most accurate biomarkers for bacteremia/sepsis discrimination were cytokines (IL-6, IL-10, IL-8), on day 2 – IL-8 and PCT. On day 1 the... [to full text]