Diagnóstico de virus respiratorios en la unidad de cuidados intensivos neonatales: ¿listos para el prime time? / Testing for respiratory viruses in the neonatal intensive care unit: ready for prime time?

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Novedades en el tratamiento de la bronquiolitis: perspectivas en el 2013 / Recent advances in the treatment of bronchiolitis: perspectives for 2013

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Daptomicina a dosis altas en infección diseminada por Staphylococcus aureus resistente a meticilina / High-dose daptomycin use in methicillin-resistant Staphylococcus aureus disseminated infection

La infección por Staphylococcus aureus resistente a meticilina asociado a la comunidad (SARM-AC) es un problema creciente en nuestro país. La daptomicina es un antibiótico bactericida con actividad frente al SARM-AC. Presentamos a 3 pacientes pediátricos con SARM-AC diseminado que recibieron daptomicina a dosis altas, con buena respuesta microbiológica y clínica(AU)

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are an increasing problem in our country. Daptomycin is a bactericidal antibiotic with activity against CA-MRSA. Experience using high-dose daptomycin is reviewed in three paediatric patients with severe-disseminated CA-MRSA infection with a favourable microbiological and clinical response(AU)

Human metapneumovirus infections are associated with severe morbidity in hospitalized children of all ages.

The impact of human metapneumovirus (HMPV) in children aged >5 years and the risk factors associated with disease severity for all ages have not been well characterized. A retrospective cohort study of 238 children aged 0­15 years hospitalized over a 3-year period was performed. Medical records were reviewed for demographic information, clinical parameters and outcomes. Multivariable analyses were performed to identify independent factors associated with worse disease severity assessed by length of hospital stay (LOS), need for ICU care, respiratory support, and a disease severity score. Pulmonary diseases were associated with all outcomes of care, while congenital heart disease (CHD) and neuromuscular disorders were associated with longer LOS, and CHD and trisomy 21 were associated with worse severity scores independent of other covariables. Fever, retractions, use of steroids and albuterol were also associated with enhanced disease severity. Understanding the determinants of HMPV disease in children may help design targeted preventive strategies.

[High-dose daptomycin use in methicillin-resistant Staphylococcus aureus disseminated infection]. / Daptomicina a dosis altas en infección diseminada por Staphylococcus aureus resistente a meticilina.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are an increasing problem in our country. Daptomycin is a bactericidal antibiotic with activity against CA-MRSA. Experience using high-dose daptomycin is reviewed in three paediatric patients with severe-disseminated CA-MRSA infection with a favourable microbiological and clinical response.

High risk for RSV bronchiolitis in late preterms and selected infants affected by rare disorders: a dilemma of specific prevention.

Respiratory syncytial virus (RSV) is the most frequent aetiologic agent that causes bronchiolitis and lower respiratory tract infection in infants. These infections may be severe and even life-threatening in selected high-risk populations. Traditional, well-established, high-risk populations are preterm infants with or without chronic lung disease and children with congenital heart disease. For these children, RSV prophylaxis using palivizumab, a monoclonal anti-RSV humanised antibody against the F-protein of RSV, has proven safe and efficacious in preventing RSV-related hospitalisation. Recently, a number of rare medical conditions have been associated with the risk of severe RSV infections. Evidence of safety and efficacy of RSV prophylaxis in these populations is lacking. Given the low incidence of these conditions, randomised trials are not feasible. A practical, opinion-based approach to this dilemma is offered in this paper. It is proposed that these rare disorders may qualify for RSV prophylaxis if the association between a specific condition and the risk of severe RSV infection is confirmed in at least 3 independent publications, of which at least 1 includes a prospective cohort study. To facilitate pharmaco-economic analyses, at least one of the three studies must also report on the absolute risk of severe RSV infection in the specified illness. The authors believe that qualification criteria will enable caregivers to target RSV prophylaxis more effectively in children with rare conditions and the proposed approach provides direction for future epidemiological studies on the risk of severe RSV infection in children with these uncommon, medical illnesses.

Respuesta inmune respiratoria al año de vida en el niño prematuro / Respiratory immune response in first year of a preterm infant

Introducción: Existe un gran desconocimiento acerca de la evolución del sistema inmune en la mucosa respiratoria del niño prematuro a largo plazo. La inmadurez y las infecciones respiratorias pueden influir sobre la respuesta inmune de las mucosas. El propósito de este estudio era evaluar la secreción respiratoria de los mediadores inmunológicos al año de vida en niños prematuros. Pacientes y métodos: Desde octubre de 2008 hasta abril de2009 se reclutaron 77 prematuros nacidos en 6 servicios de pediatría de Castilla y León, así como 14 controles sanos a término. Los prematuros fueron citados al año de edad gestacional corregida y los niños a término al año de vida, momento en el cual se les realizó un lavado nasal para determinar los niveles de 27 mediadores inmunológicos mediante un ensayo de Biorad®. Resultados: Los niños prematuros tenían niveles más elevados de quimiocinas (eotaxina, IP-10), citocinas Th-1 (IFN-epsilon), Th-2 (IL-13), Th-17 (IL-17) y factores de crecimiento celular (PDGF-bb, VEGF, FGF-b, G-CSF y GM-CSF) que los niños a término. Cuando se compararon los niveles de mediadores entre los niños que habían recibido profilaxis para el virus respiratorios incitial con palivizumab y los que no, los segundos tenían niveles significativamente más altos de MCP-1, IL-1RA, IL-10,IL-12p70 y VEGF (p <0,05) que los primeros. Conclusiones: Este trabajo demuestra por vez primera la influencia de la prematuridad sobre los perfiles de secreción respiratoria de las citocinas y quimiocinas a largo plazo. Por otra parte, nuestros resultados indican que la evaluación del impacto de la profilaxis de la infección respiratoria es un camino interesante para comprender la maduración de la respuesta inmune de la mucosa respiratoria del prematuro(AU)

Introduction: There is a big unawareness about a long term respiratory mucous immune system evolution in the preterm infant. Immaturity and respiratory infections can have a big influence on the mucous immune responses. This investigation’s purpose is the evaluation of respiratory secretion of inflammatory immunological mediators in the first year of a preterm infant. Patients and methods: Between October 2008 and April 2009, 77 preterm infants were born in 6 pediatric services of Castilla y Leon, plus to another 14 healthy controls results. Children were invited on their first corrected gestational age and the ones of healthy controls results. Nasal washing were applied to determine 27 immunological mediators’ levels by applying a Biorad test. Results: The preterm infants has higher chemokine (eotaxin,IP-10), cytokines Th-1 (IFN-epsilon), Th-2 (IL-13), Th-17 (IL-17) and cell growing factors (PDGF-bb, VEGF, FGF-b, G-CSF and GM-CSF)levels than a healthy control results children. When a comparison was made between children that received prophylaxis for their respiratory syncytial virus with palivizumab and the ones that did not receive it, the second group showed higher MCP-1, IL-1RA, IL-10, IL-12p70 and VEGF (p <0,05) levels. Conclusions: This work proves, for the first time, the influence of the premature birth on chemokine and cytokines respiratory secretion levels in a long term concepts. On other hand, our results indicate that prophylaxis impact in the respiratory infection is an interesting way to understand respiratory mucous immune response maturation in the preterm infant(AU)

The relationship between RSV bronchiolitis and recurrent wheeze: the chicken and the egg.

Respiratory syncytial virus bronchiolitis is the most frequent cause of infant hospitalization. RSV bronchiolitis is often followed by recurrent episodes of wheeze. Pathogenesis of RSV bronchiolitis as well as post-bronchiolitis wheeze are incompletely understood. The aim of this review is to provide a brief overview of our current understanding of the complex pathogenesis of RSV bronchiolitis and post-bronchiolitis wheeze. Two non-exclusive hypotheses exist, which are paraphrased for this review as "the chicken and the egg". First, we reviewed the pre-existent genetic, pulmonary and immunological mechanisms of RSV bronchiolitis and post-bronchiolitis wheeze. Second, RSV as the causative virus of long-term airway morbidity is reviewed. Clearly, RSV infection is capable of causing direct damage to the airways and/or inducing long-term inappropriate immune responses to respiratory viruses or aero-allergens. It is concluded that intervention trials aimed at preventing RSV infections are required to establish the relative contribution of both RSV-induced and pre-existent mechanisms to the development of long-term airway disease following RSV bronchiolitis.

Infecciones por virus respiratorio sincitial. Antiguos retos y nuevas estrategias / Respiratory syncytial virus infections. Old challenges and new strategies

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Severe neonatal hypoxic respiratory failure correlates with histological chorioamnionitis and raised concentrations of interleukin 6 (IL6), IL8 and C-reactive protein.

BACKGROUND: The mechanisms contributing to hypoxic respiratory failure (HRF) in term infants are multifactorial. Recent evidence suggests a potential pathogenetic role for inflammation. Nitric oxide (NO), a pulmonary vasodilator, is inhibited by inflammatory mediators that are upregulated in the presence of placental inflammation. OBJECTIVE: To examine the relationship between histological chorioamnionitis and/or funisitis, serum concentrations of inflammatory mediators and severity of HRF. METHODS: Prospective observational study involving term neonates with HRF and normal controls. Blood samples were taken at birth from mixed cord blood, at 6 h and 30 h for cytokines and CRP, and at 72 h and 96 h for CRP. Placentas were examined for chorioamnionitis. The primary outcome was the administration of inhaled nitric oxide (iNO) therapy. Data were analysed using analysis of variance and chi(2) analysis. RESULTS: 32 neonates with hypoxic respiratory failure and 25 controls were enrolled. 14/32 (44%) neonates with HRF required iNO, 9/32 (28%) required high-frequency ventilation and 3/32 (9%) required ECMO; 2/32 (6%) died. Neonates with HRF had more than threefold higher cord levels of interleukin 8 (IL8) than the controls (p<0.05). At 6 h and 30 h, serum IL6, IL8 and CRP were > or =2.2-fold higher in neonates who received iNO (p<0.003). 23/32 (72%) infants with HRF had evidence of histological chorioamnionitis and/or funisitis compared with 5/25 (20%) controls (p<0.001). CONCLUSION: Severe HRF, as defined by the need for iNO, is associated with raised blood levels of proinflammatory mediators and increased occurrence of histological chorioamnionitis and funisitis, suggesting that inflammation contributes to the severity of hypoxic failure.

[Asthma and respiratory syncytial virus. New opportunities for therapeutic intervention]. / Asma y virus respiratorio sincitial. Nuevas oportunidades de intervención terapéutica.

Numerous studies have described an association between respiratory sincticial virus (RSV) infection in infancy and the subsequent development of airway hyperresponsiveness (AHR). Besides the exaggerated immune response and the abnormal neurogenic mechanisms induced by RSV, recent studies have correlated the "persistence" of RSV in the lower respiratory tract with the development of AHR. Several investigators have evaluated whether treatment with antiviral or immunosuppressive agents could decrease the long term respiratory abnormalities induced by RSV. The RSV murine model has allowed us to study the immunopathogenesis of RSV-induced AHR. Once the airway obstruction, typical of acute disease, is resolved and no virus is longer detected by cell cultures, mice progress into a chronic phase characterized by AHR and persistent airway inflammation. The use of polymerase chain reaction assay for RSV quantitation has demonstrated, quite unexpectedly, the presence of RSV RNA in the lower respiratory tract of mice during the chronic phase of the disease. As an example of intervention, the administration of an anti-RSV neutralizing antibody (palivizumab) was associated with a significant reduction in viral replication, pulmonary inflammation and inflammatory cytokines, as well as a significant improvement in the pulmonary function both in the acute and chronic phases of the disease. Future clinical studies to determine whether therapy with palivizumab can prevent the long-term morbidity associated with RSV in children are warranted.

Asma y virus respiratorio sincitial. Nuevas oportunidades de intervención terapéutica / Asthma and respiratory syncytial virus. New opportunities for therapeutic intervention

Numerosos estudios han descrito la asociación entre la infección por virus respiratorio sincitial (VRS) en la infancia y el desarrollo posterior de hiperreactividad bronquial (HRB). Además de la respuesta inmunitaria exagerada y las alteraciones de los mecanismos neuronales,estudios recientes han relacionado la posible "persistencia" del VRS en el tracto respiratorio inferior con la patogenia de la HRB. Varios investigadores han analizado si el tratamiento de la bronquiolitis con fármacos antivirales o inmunosupresores podría disminuir las secuelas pulmonares ocasionadas por el VRS. El modelo experimental de VRS en el ratón ha permitido estudiar la inmunopatogenia de la infección por VRS. Una vez que se resuelve la fase aguda de obstrucción de la vía aérea y no se puede detectar el virus en cultivo celular, los ratones progresan hacia una fase crónica caracterizada por HRB e inflamación persistente de la vía aérea. La utilización de la reacción en cadena de polimerasa (PCR) ha permitido, de forma inesperada, la detección de ARN de VRS en el tracto respiratorio en esta fase crónica. Como ejemplo de intervención, la administración del anticuerpo neutralizante anti-VRS (palivizumab) se asoció a una reducción significativa de la replicación viral, de la inflamación pulmonary de las citocinas inflamatorias y a una mejoría significativa en las pruebas de función pulmonar en las fases aguda y crónica de la enfermedad. Estos resultados llevan a proponer la realización de estudios clínicos para evaluar el papel de palivizumab en la prevención de las secuelas pulmonares causadas por el VRS en la población pediátrica (AU)

An anti-CD45RO immunotoxin kills HIV-latently infected cells from individuals on HAART with little effect on CD8 memory.

CD4+ CD45RO+ T cells are the major latent viral reservoir in HIV-infected individuals and hence a major obstacle in curing the disease. An anti-CD45RO immunotoxin (IT) can decrease the number of both productively and latently infected CD4+ T cells obtained from HIV-infected individuals with detectable viremia. In this study, we determined whether this IT could also kill latently infected replication-competent CD4+ T cells obtained from infected individuals without detectable plasma viremia. Our results demonstrate that ex vivo treatment with the anti-CD45RO IT significantly reduced the frequency of these cells. In contrast, the IT had only a modest effect on the cytomegalovirus-specific memory responses of CD8+ T cells. These results suggest that purging latent cells from infected individuals on highly active antiretroviral therapy with the anti-CD45RO IT might reduce the HIV latent reservoir without seriously compromising CD8+ T cell memory responses.

Virus respiratorio sincitial: antiguos retos y nuevas estrategias / No disponible

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Asma y virus respiratorio sincitial: ¿mito o realidad? / Asthma and respiratory syncytial virus. Myth or reality?

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