This article addresses some current issues about genetic polymorphisms studied in the non-small-cell lung cancer translational field. Furthermore, it discusses about new potential biomarkers regarding lung cancer risk and prognosis. Patients in stage IV according to the TNM Classification of Malignant Tumors, of the American Joint Cancer Committee (AJCC), have a median overall survival (OS) of 10 to 11 months after the treatments. In 2011, the group from the University of Porto and University of Minho, in Portugal, published a review that emphasized various studies related to the treatment of the advanced disease using treatments directed towards the main molecular pathways responsible for the carcinogenesis of NSCLC. The epidermal growth factor (EGF) and its receptor, EGFR, have been shown to be very significant pathways in the carcinogenesis of lung neoplasm. The mutation of the EGFR at exons 19 and 21 was recently described as a predictor of a good response to the therapeutic use of tyrosine kinase inhibitors as a first, second, or third line of systemic treatment for advanced NSCLC, especially adenocarcinomas in non-smokers and Asians.-9 Additionally, the vascular endothelial growth factor (VEGF) is also intimately related to carcinogenesis of NSCLC. Some studies-12 showed that certain genetic polymorphisms responsible for the regulation of the VEGF pathway may be associated with risk and prognosis in patients with NSCLC. In this way, the objective of this article was to briefly review important aspects related to the main target-therapies approved for treating advanced NSCLC and potential biomarkers.Currently, non-small cell lung cancer (NSCLC) is a neoplasm of worldwide importance due to its high incidence and mortality. Nevertheless, posterior analysis of these results implied discontinuation of bevacizumab in advanced NSCLC since the cost-benefit association was not confirmed as to an increase in OS (only about 2 months), according to the European Medicines Agency (EMA).In 2009, the AVAiL study was very important for the approval, in Europe and the United States, of the use of bevacizumab, a monoclonal antibody against VEGF, in advanced-stage NSCLC. demonstrated the superiority of geftinib, an EGFR tyrosine kinase inhibitor as first line treatment of patients with advanced NSCLC, presenting with EGFR mutation at exons 19 and 21. Since then, there has been a great advance in the treatment results of these patients. The EGFR tyrosine kinase inhibitors showed excellent results as to longer OS in stage-IV patients, mutated EGFR, and especially Asian non-smokers.In 2010, other studies-19 Some studies in this regard,,17,20-23 although yet with small number of patients, demonstrated that crizotinib, an ALK tyrosine kinase inhibitor, showed an excellent overall response (approximately 57%) to treatment in EML4-ALK-positive patients with advanced disease.,17,20-23 Thus, the role of EML4-ALK and of crizotinib seems to be promising within this context, although broader Phase II studies are necessary to establish, with detail, all these aspects.The fusion of EML4-ALK (echinoderm microtubule-associated protein-like 4 – anaplastic lymphoma kinase) was identified as having a significant role in the clinical management of a small subgroup of patients (about 6%) with NSCLC, especially adenocarcinomas, who were non-smokers and young. In 2012, in Portugal, our group was able to demonstrate an association between the susceptibility of the NSCLC and genetic polymorphism of EGF+61 A/G.(25) Considering that the determination of this genetic polymorphism consists of a low-cost and practical test, since it is obtained from peripheral blood samples, we believe that the use of this biomarker may be useful in the future for improving tracking of lung carcinoma, optimizing the selection of patients elegible for low-dose chest CAT, and consequently, the financial resources available for this imaging test. On the other hand, we also know that the evaluation of germinating line genetic polymorphisms is performed by DNA extraction of peripheral blood using complete blood count (CBC) tubes containing EDTA (ethylenediaminetetraacetic acid). Thus, the implementation of certain genetic polymorphisms in clinical practice is extremely practical and feasible, with the potential to generate great benefit for the patients considered.,27 Keeping these aspects in mind, a strong new trend in studies arises, which tries to investigate the role of genetic polymorphisms as prognostic biomarkers for NSCLC. Those that stand out are the pathways linking VEGF and the CLPTM1L .,28 By means of genome wide association studies  polymorphic variants of susceptibility to lung cancer were detected in chromosomes 5p15.33, 6p21, and 15q25. Specifically, the variants rs2736100, located at intron 2 of telomerase reverse transcriptase (TERT) and rs401681 of CLPTM1L C/T, in 5p15.33, are associated with lung adenocarcinomas.There is, however, a great need to try to stratify patients using biomarkers related specifically to the risk of developing the neoplasm and to the prognosis in various stages. Nevertheless, a few practical questions also arise: to what extent is it possible to obtain biological samples for biomarker investigation? Are there plausible instruments for intervention in this stratified population? Can these approaches, in fact, influence the clinical progression of these patients? Currently, by the recommendations of the National Cancer Comprehensive Network (NCCN), in the United States, approve the use for low-dose computed axial tomography (CAT) of the chest to trace lung carcinoma in individuals aged over 55 years and a smoking load of more than 30 pack-years (PYs).Therefore, from this point on, genetic polymorphisms have become an emphasized theme in translational studies, with the objective of creating a bridge between basic research and clinical applicability for the study of NSCLC in several European and worldwide centers.Finally, the clinical and therapeutic approaches of lung cancer have had great advances over the last few decades by means of translational studies that identified predictive biomarkers already established in clinical practice, such as the of EGFR mutation and the of ALK-EML4 fusion. These are associated with the choice of target therapies, such as erlotinib, gefitinib and, more recently, crizotinib. In the future, new biomarkers should appear with the use of certain polymorphic variations of the germinative line, such as EGF+61 A/G,VEGF – 460 C/T, and CLPTM1L C/T, as biomarkers of risk and prognosis of non-small cell lung cancer, and may be an additional help to clinical oncologists during treatment of these patients. Nevertheless, prospective and randomized studies are still necessary to validate the potential value of these findings.  Doentes com estádio IV, de acordo com a Classificação de Tumores Malignos (Classificação TNM), do American Joint Cancer Comittee (AJCC), apresentam uma sobrevivência global (SG) mediana de 10 a 11 meses após os tratamentos. Em 2011, o grupo da Universidade do Porto e da Universidade do Minho, em Portugal, publicou revisão que enfatizou os vários estudos relacionados ao tratamento da doença avançada utilizando terapêuticas dirigidas às principais vias moleculares responsáveis pela carcinogênese do CPCNP. O fator de crescimento epidérmico  e seu receptor (EGFR) têm sido demonstrados como vias muito importantes na carcinogênese da neoplasia do pulmão. A mutação do EGFR nos éxons 19 e 21 foi recentemente descrita como preditora de boa resposta ao uso de terapêuticas inibidoras da tirosina quinase em primeira, segunda ou terceira linha de tratamento sistêmico para CPCNP avançado, especialmente os adenocarcinomas, não fumantes e asiáticos.-9 Além disso, o factor de crecimento endotelial vascular  também encontra-se intimamente relacionado com a carcinogênese do CPCNP. Alguns estudos-12 mostraram que determinados polimorfismos genéticos responsáveis pela regulação da via do VEGF podem estar associados ao risco e ao prognóstico em doentes com CPCNP. Dessa forma, o objetivo deste artigo foi rever brevemente aspectos importantes relacionados às principais terapêuticas-alvo aprovadas para o tratamento do CPCNP avançado e potenciais biomarcadores.Atualmente, o carcinoma de pulmão de células não pequenas (CPCNP) consiste numa neoplasia de importância mundial, devido à sua elevada incidência e mortalidade. No entanto, a análise posterior desses resultados implicou na retirada da utilização do bevacizumabe no CPCNP avançado, pois, segundo a European Medicines Agency (EMA), não se comprovou a relação custo-benefício, no que diz respeito ao aumento da SG (cerca de apenas 2 meses).Em 2009, o estudo AVAiL foi bastante importante para a aprovação, na Europa e nos Estados Unidos, da utilização do bevacizumabe, um anti-corpo monoclonal contra o VEGF, no CPCNP em estádio avançado. demonstraram a superioridade do geftinib, um inibidor da tirosina quinase do EGFR, no tratamento de primeira linha de pacientes com CPCNP avançado, apresentando a mutação do EGFR nos éxons 19 e 21. A partir de então, houve grande avanço nos resultados do tratamento desses pacientes. Os fármacos inibidores da tirosina quinase do EGFR mostraram excelentes resultados no que diz respeito ao aumento da SG nos doentes em estádio IV, EGFR mutado e principalmente não fumantes asiáticos.Em 2010, outros estudos echinoderm microtubule-associated protein-like 4 – anaplastic lymphoma kinase) foi identificada como tendo um importante papel na abordagem clínica de um pequeno subgrupo de pacientes (cerca de 6%) com CPCNP, especialmente adenocarcinomas, não fumantes e jovens.-19 Nesse contexto, alguns estudos,,17,20-23 embora ainda com poucos pacientes, demostraram que o crizotinib, uma molécula inibidora da tirosina quinase do ALK, apresentou excelente resposta global (aproximadamente 57%) ao tratamento em pacientes com doença avançada EML4-ALK positivos.,17,20-23 Assim, o papel do EML4-ALK e do crizotinib parece promissor nesse contexto, embora estudos mais alargados, de fase II, são necessários para estabelecer, com pormenores, todos esses aspectos.A fusão do EML4-ALK , a utilização de tomografia-axial-computadorizada (TAC) torácica de baixa dose para o rastreio do carcinoma de pulmão em indivíduos com mais de 55 anos e carga tabágica acima de 30 Unidades Maço Ano (UMA). Em 2012, em Portugal, o nosso grupo conseguiu demonstrar uma associação entre a suscetibilidade do CPCNP e o polimorfismo genético do EGF+61 A/G. Considerando que a determinação desse polimorfismo genético consiste num exame de baixo custo e bastante prático, por ser obtido de amostras de sangue periférico, acreditamos que a utilização desse biomarcador pode, no futuro, ser útil para melhorar o rastreio do carcinoma de pulmão, otimizando a seleção de pacientes elegíveis para TAC de baixa dose e, consequentemente, os recursos financeiros disponíveis para esse exame de imagem. Por outro lado, também sabemos que a avaliação de polimorfismos genéticos da linha germinativa são efetuados por meio da extração de DNA por sangue periférico, utilizando tubos de hemograma, contendo EDTA (do inglês ethylenediaminetetraacetic acid). Assim, a implementação de determinados polimorfismos genéticos na prática clínica é algo extremamente prático e factível, com o potencial de gerar grande benefício para os pacientes em questão.,27 Tendo em vista esses aspectos, nasce uma forte vertente de estudos, que tentam investigar o papel de polimorfismos genéticos como biomarcadores de prognóstico do CPCNP. Em destaque, estão as vias do ligando VEGF e do receptor do CLPTM1L .,28 Por meio de estudos de associação de genoma completo  foram detectadas variantes polimórficas de suscetibilidade ao câncer de pulmão nos cromossomo 5p15.33, 6p21 e 15q25. Especificamente, as variantes rs2736100, localizadas no íntron 2 do TERT (telomerase reverse transcriptase) e rs401681 do (CLPTM1L C/T), em 5p15.33, estão associadas a adenocarcinomas do pulmão.Há, portanto, uma imensa necessidade de tentar estratificar os pacientes utilizando-se biomarcadores relacionados especificamente ao risco de desenvolver a neoplasia e ao prognóstico em diversos estádios. No entanto, surgem também algumas perguntas práticas: até que ponto é possível obter amostras biológicas para a pesquisa de biomarcadores? Existem instrumentos plausíveis para intervir nessa população estratificada? Será que essas abordagens podem influenciar, de fato, a evolução clínica desses pacientes? Atualmente, foi aprovada, pelas recomendações americanas do Portanto, a partir desse ponto, os polimorfismos genéticos passaram a ser um tema de destaque em estudos translacionais, com o objetivo de criar uma ponte entre a pesquisa básica e a aplicabilidade clínica para o estudo do CPCNP em vários centros europeus e ao nível mundial.Em resumo, as abordagens clínica e terapêutica do carcinoma de pulmão tiveram um grande avanço nas últimas décadas, por meio de estudos translacionais que identificaram biomarcadores preditivos já estabelecidos na prática clínica, como a mutação do EGFR e a fusão ALK-EML4, que se econtram associados à escolha de terapêuticas-alvo como o erlotinibe, gefitinibe e, mais recentemente, o crizotinib. No futuro, novos biomarcadores devem surgir, por meio da utilização de determinadas variações polimórficas da linha germinativa, como o EGF+61 A/G, o VEGF – 460 C/T e o CLPTM1L C/T, como biomarcadores de risco e prognóstico do carcinoma de pulmão de células não pequenas, podendo constituir uma ajuda adicional aos oncologistas clínicos durante a abordagem desses pacientes. No entanto, estudos prospectivos e randomizados são ainda necessários para validar o potencial valor desses achados.


Aedes aegypti larvae were found in a natural breeding site in the Pinheiros neighborhood, city of Sao Paulo, SP, Southeastern Brazil. The record was conducted in December 2014, during an entomological surveillance program of dengue virus vectors, with an active search of potential breeding sites, either artificial or natural. Finding Ae. aegypti larvae in a tree hole shows this species’ ability to use both artificial and natural environments as breeding sites and habitats, which points towards the importance of maintaining continuous surveillance on this mosquito in all kinds of water-holding containers.This is the description of how nine  Aedes (Stegomyia) aegypti  is considered a mosquito of great importance to public health care since the early 20th century, when it was found to be a vector of urban yellow fever. Currently, Ae. aegypti is considered the main vector of the four dengue virus serotypes circulating in Brazil , besides being a competent enough vector to transmit the arboviruses chikungunya and Zika, which have just arrived in the countryAe. aegypti is most frequently found in urban and sub-urban environments, with high concentrations of human beings and houses. Present in all Brazilian states, the females of this species often lay their eggs in rainwater deposits such as artificial containers or objects for domestic use, such as tires, cans, bottles, flower pots, water reservoirs, barrels, vats, abandoned swimming pools and aquariums, among others1. However, albeit rarely, some studies report the finding of Ae. aegypti larvae in bromeliad plants in urban areas,The behavior of this vector is highly endophilic and anthropophilic; it seeks shelter inside houses, where it feeds from human blood. Thus, No efficient vaccines are currently available against dengue fever, chikungunya, or Zika. Thus, the only controllable element in the epidemiological chain of these arboviruses is the mosquito, and the main strategy to control that vector mainly includes eliminating its potential breeding sitesAe. aegypti larvae in a natural breeding site in an urban area of the city of Sao Paulo, during entomological surveillance procedures.This study aimed to report the finding of Ae. aegypti immatures was conducted in both artificial and natural breeding sites on December 3, 2014, in an urban area located in the Pinheiros neighborhood, city of Sao Paulo, SP, Southeastern Brazil, which is a very busy area.An active search for Plastic ladles with maximum capacity of 80 ml were used to collect the immatures. The material collected with the ladles was transferred to plastic containers labeled according to the types of breeding sites, and then sent to an entomology laboratory. The collected larvae were identified under a stereo microscope, according to the dichotomous key proposed by Consoli and Lourenço de OliveiraAe. aegypti and kept in a laboratory until they fully matured, when their species was confirmed.Nine larvae in the L4 stage were collected in a hole of a tree that belonged to the Moraceae family and to the Ficus genus , A and BAe. aegypti show that this mosquito is more frequently captured inside houses, and female mosquitoes are found to be engorged with human blood. That reinforces the endophilic and anthropophilic behaviors of that speciesAe. aegypti in immature stages is more frequent in artificial breeding sites in urban and sub-urban areas, although larvae of this species have already been found in natural breeding sites, such as bromeliad plants,In Brazil, field studies with Ae. aegypti larvae in a tree hole near some houses, during a search for potential breeding sites of this vector in the area. Finding L4 stage Ae. aegypti larvae in a natural breeding site points towards two important aspects. The first is that entomological surveillance on this species in artificial containers may have been efficient, as the reduced availability of that type of breeding site causes Ae. aegypti to seek other places to lay its eggs. The second aspect is the confirmed plasticity of this vector, which, in the absence of artificial breeding sites, lays its eggs in natural breeding sites, a behavior that is not very usual for this species.This study reports the finding of nine Ae. aegypti not only in artificial containers but also in natural water-holding surfaces, even in urban areas, to keep outbreaks of arboviruses such as dengue, chikungunya, and Zika controlled.In conclusion, it is necessary to maintain entomological surveillance on  Aedes (Stegomyia) aegypti  é considerado mosquito de grande importância para a saúde pública desde o início do século XX, quando foi incriminado como vetor da febre amarela urbana. Atualmente, Ae. aegypti é considerado o principal vetor dos quatro sorotipos do vírus dengue circulantes no Brasil , além de apresentar elevada competência vetorial para transmitir os arbovírus chikungunya e Zika, recém-emergidos no PaísAe. aegypti ocorre, principalmente, em ambientes urbanos e suburbanos, onde há elevada concentração populacional humana e de residências. Presente em todos os estados brasileiros, as fêmeas dessa espécie frequentemente depositam seus ovos em recipientes artificiais com água da chuva ou de uso doméstico, como pneus, latas, vidros, garrafas, pratos de vasos, caixas d’água, tonéis, latões, piscinas e aquários abandonados, entre outrosAe. aegypti em bromélias localizadas em áreas urbanas,O comportamento desse vetor é altamente endofílico e antropofílico; ele utiliza o interior das casas para se abrigar e alimentar-se do sangue humano. Dessa forma, o encontro de Atualmente, não estão disponibilizadas vacinas eficazes contra dengue, chikungunya e Zika. Assim, o único elemento da cadeia epidemiológica dessas arboviroses que pode ser controlado é o mosquito, e a principal estratégia de controle desse vetor envolve, principalmente, a eliminação dos seus criadouros potenciaisAe. aegypti em criadouro natural de área urbana da cidade de São Paulo, durante procedimentos de vigilância entomológica.Este estudo teve como objetivo relatar o encontro de larvas de Ae. aegypti em criadouros artificiais e naturais em área urbana localizada no bairro de Pinheiros, São Paulo, SP, com grande circulação de pessoas.Em 3 de dezembro de 2014, foi realizada busca ativa de imaturos de Para a coleta dos imaturos, foram utilizadas conchas plásticas, com capacidade máxima de 80 ml. O material coletado com as conchas foi transferido para vasilhas de plástico, etiquetadas de acordo com o tipo de criadouro, e enviadas para laboratório de entomologia. As larvas coletadas foram identificadas sob microscópio estereoscópico, seguindo chave dicotômica proposta por Consoli e Lourenço de OliveiraFicus (Ae. aegypti e mantidas em laboratório até a emergência dos adultos, quando foi feita a confirmação da espécie.Nove larvas em estádio L4 foram coletadas em oco de árvore, pertencente à Família Moraceae e ao gênero Ficus , A e B. Ae. aegypti mostram que esse mosquito é mais frequentemente capturado no intradomicílio, com as fêmeas ingurgitadas apresentando sangue de origem humana no estômago. Isso reforça o comportamento endofílico e antropofílico da espécieAe. aegypti é mais frequente em criadouros artificiais de áreas urbanas e suburbanas, embora larvas dessa espécie já tenham sido registradas em criadouros naturais, como bromélias,No Brasil, os estudos realizados em campo com Ae. aegypti em oco de árvore em peridomicílio, durante busca por criadouros potenciais do vetor nessa área. O encontro de larvas de quarto estádio de Ae. aegypti em criadouro natural aponta para dois aspectos importantes. O primeiro deles é que a vigilância entomológica sobre essa espécie em recipientes artificiais pode estar sendo eficiente, pois a redução da oferta desse tipo de criadouro faz com que o Ae. aegypti busque outros locais para realizar a oviposição. O segundo aspecto é a comprovação da plasticidade desse vetor que, na ausência dos criadouros artificiais, deposita seus ovos em criadouros naturais, comportamento pouco frequente para a espécie.Neste estudo, foi relatado o encontro de nove larvas de Ae. aegypti não só em recipientes artificiais, mas também em naturais, mesmo em áreas urbanas, a fim de serem controlados surtos de arboviroses, como dengue, chikungunya e Zika.Em conclusão, faz-se necessária a manutenção da vigilância entomológica do


To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya.We followed up children aged 2–59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs.P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI −0.84 to 0.51)].We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4–5.1) and 12.4% (95% CI 7.9–18.4) for SP and 21.4% (95% CI 15.9–27) and 39.3% (95% CI 32.5–46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment  chez les enfants hospitalisés avec une pneumonie acquise dans la communauté dans un grand hôpital tertiaire du Kenya.Nous avons suivi des enfants âgés de 2 à 59 mois avec une pneumonie sévère (PS) et une pneumonie très sévère (PTS) telles que définies par l’OMS, sur un maximum de cinq jours pour l’ET, en utilisant deux définitions: (a) documentation des signes cliniques prédéfinis ayant entraîné un changement du traitement, (b) décision primaire du clinicien de changer de traitement avec ou sans documentation des mêmes signes cliniques prédéfinis.Nous avons recruté 385 enfants. Le risque d’ET variait de 1,8%  à 12,4%  pour la PS et de 21,4%  à 39,3%  pour la PTS selon la définition appliquée. Des taux plus élevés étaient associés à des changements précoces du traitement par le clinicien en l'absence d'une justification clinique évidente. Le non-respect des directives de traitement a été observé pour 70/169  et 67/201  enfants avec une PS et une PTS respectivement. Chez les enfants avec une PS, le respect des directives de traitement était associé avec la présence d'une respiration sifflante au cours l’évaluation initiale  tandis que le non respect par les cliniciens des traitements recommandés pour la PTS tendait à se produire chez les enfants avec une altération de la conscience . L'utilisation du score de propension correspondant pour tenir compte du déséquilibre dans la répartition des caractéristiques cliniques de base chez les enfants avec une PTS n'a révélé aucune différence dans l’ET entre ceux traités avec le régime recommandé par les directives et ceux traités par des alternatives plus coûteuses à large spectre .Avant la révision des directives actuelles de prise en charge des cas de pneumonie, des définitions standard d’ET et des études appropriées de l'efficacité des traitements alternatifs sont nécessaires.Determinar la extensión y el patrón del fallo en el tratamiento (FT) en niños hospitalizados con una neumonía adquirida en la comunidad, ingresados en un gran hospital terciario de Kenia.Hemos seguido a niños con edades entre los 2-59 meses con una neumonía severa (NS) y neumonía muy severa (NMS) según definición de la OMS de hasta cinco días para FT utilizando dos definiciones: (a) documentación de signos clínicos pre-definidos que resultaron en un cambio de tratamiento (b) decisión del clínico principal de cambiar el tratamiento con o sin documentación de los mismos signos clínicos pre-definidos.Incluimos a 385 niños. El riesgo de FT varió entre un 1.8% (IC 95% 0.4 a 5.1) y 12.4% (IC 95% 7.9 a 18.4) para NS y 21.4% (IC 95% 15.9 a 27) y 39.3% (IC 95% 32.5 a 46.4) para NMS dependiendo de la definición que se aplicase. Unas mayores tasas estaban asociadas con cambios tempranos en la terapia por el clínico y en ausencia de un razonamiento clínico obvio. Se observaba una no adherencia a las guías de tratamiento en 70/169 (41.4%) y 67/201 (33.3%) de los niños con NS y NMS respectivamente. Entre los niños con SP, la adherencia a las guías de tratamiento estaba asociada con la presencia de sibilancias en la evaluación inicial (P=0.02) mientras que la no adherencia del clínico a los tratamientos recomendados por las guías para NMS tendían a ocurrir en niños con un estado alterado de consciencia (P<0.001). Utilizando el pareamiento por puntaje de propensión para equilibrar los grupos en la distribución de las características clínicas de base de los niños con NMS, se observó que no existían diferencias en FT entre aquellos tratados con el régimen recomendado por las guías versus alternativas más costosas de amplio espectro (diferencias de riesgo 0.37 (IC 95% -0.84 a 0.51).Antes de revisar las actuales guías de manejo de casos de neumonía, se requieren definiciones estandarizadas de FT y estudios apropiados de la efectividad del tratamiento de regímenes alternativos. Pneumonia is the leading cause of childhood mortality, responsible for nearly one and a half million annual deaths . Over thHaemophilus influenzae type b (Hib) vaccine  the emergence of antibiotic resistance, particularly to penicillin  and mortality have helped inform discussion around revision of guidelines, particularly in Asia  that receives an average of 900 paediatric admissions per month. Despite being a national hospital, a large proportion of patients present directly from home, bypassing lower levels of care.Children aged 2–59 months satisfying the WHO case definitions for SP or VSP Table  whose caUsing estimates from previous Kenyan studies . Children with saturations below 90% after breathing ambient air for a minimum of 3 min were deemed hypoxemic and received supplementary oxygen in accordance with local practice.Blood samples were collected before administration of antibiotics for bacterial culture . Routine, rapid HIV testing was requested for all children, according to the Government of Kenya guidelines for provider-initiated testing and counselling (PITC) (Government of Kenya 2009) and confirmatory HIV-1 DNA PCR performed for any child <18 months old with a positive rapid HIV test (Roche AMPLICOR HIV-1 test version 1.5).A detailed description of the criteria we used to define TF among children with SP and VSP is shown in Table a priori definition, a modified post-hoc definition (described in the results) and cumulative mortality at day 5 post-recruitment. Variables considered to be associated with the outcomes were used to fit the full model, and using a backward stepwise selection procedure with a pre-defined cut-off P-value of 0.2, variables were selected out one at a time until the final model was obtained. Adjusted odds ratios for association were then reported with accompanying 95% confidence intervals.Completed questionnaires were double-entered and verified using Epidata Version 3.0  and data analysed using Stata Version 11 . The primary aims of analysis were to estimate the prevalence and determine the clinical as well as sociodemographical correlates of prospectively-defined TF and mortality. To address the latter aims, chi-square or Fisher's exact test, one-way analysis of variance or the Kruskal–Wallis test was used as appropriate to explore differences in patient groups or initial associations between risk factors and outcomes. We also fitted logistic regression models to identify independent predictors of TF using the In post-hoc analyses, we further sought to compare the effectiveness of the guideline-recommended treatments against alternative regimens frequently used by clinicians among children with VSP. To address this objective, crude comparisons of clinical outcomes among children recruited in the study and treated according to the recommended guidelines against those treated with alternative regimens would be prone to selection bias arising from differences in baseline clinical characteristics, which may influence the prescribing patterns of clinicians. Thus, children who were perceived to have more severe forms of disease were more likely to have been assigned treatments perceived to be more effective by the primary clinician and vice versa. To account for this potential bias, we fitted a multivariable logistic regression model with treatment assigned as the dependent variable and sociodemographical/clinical characteristics at the time of admission as covariates to generate a propensity score for each subject adjusting for baseline clinical characteristics among recruited children. Matching patients in the two treatment groups of interest on the propensity scores generated, we derived an estimate of the average treatment effect among those treated with more aggressive regimens for which we calculated a 95% confidence interval.Between June and October 2009, 593 children were admitted at KNH with a diagnosis of probable SP or VSP of whom 487 (82%) were screened for eligibility Figure . ExclusiOf the 385 enrolled, 171 (44.4%) has SP and 214 (55.6%) VSP. Seven children died during the process of admission before full assessment, and data collection could be completed and were therefore excluded from analyses for TF and mortality. A further eight children (two with SP and six with VSP) were lost to follow-up within 24 h of recruitment. Although the investigating team initiated first-line antibiotic treatment as per the WHO/national guidelines, treatment was changed by ward-based clinical teams  and deviated from guidelines in 37.0% (137/370) of cases. The impact of such decisions on overall observed rates of TF is discussed below. Further, this non-adherence to recommended regimens necessitated division of patients into five groups for analysis , absence of improvement after 48 h of therapy, or microbiological or radiological indications for switching treatment where this information was available  were observed with rates of 3/169  for SP and 43/201  for VSP . Factors found to be independently associated with TF were grunting , younger age group – 2–11 months , inability to drink  and confirmed HIV-positive status . Characteristics associated with mortality were female gender , inability to drink  and rapid antibody test positive HIV status .Among children with VSP predictors of TF were more consistent using both pre-defined and es Table . In a muP = 0.04) and were more likely to have a history or signs of wheeze at initial assessment . Among those with VSP, children on recommended treatment had received antibiotics prior to admission less frequently  but were less likely to have altered consciousness  or inability to drink/breastfeed  than those given non-recommended treatments. A regimen of penicillin monotherapy, despite meeting the case definition for VSP, was associated with the absence of grunting .We explored differences in baseline characteristics across the treatment subgroups of children within their severity strata. Continuous data plotted on histograms showed deviation from the normal distribution. We therefore used the Kruskal–Wallis test to compare medians and chi-square test for categorical data. Significant variation between subgroups would suggest that decisions to deviate from the recommended treatment guidelines were not random. In children with SP, we found those started on recommended treatment had shorter duration of illness  were compared with those who received alternative broad-spectrum antibiotics  (34/168). The crude risk difference of TF was 0.20 (95% CI 0.02–0.38);a final model comparing the treatment groups using propensity scores calculated to account for baseline imbalances between the groups yielded a risk difference of 0.37 (95% CI −0.84–0.51).Streptococcus pneumoniae, three Salmonella typhimurium, two Escherichia coli and one Pseudomonas aeruginosa). The child from whom Pseudomonas was isolated died.Samples were collected for blood culture on 338/385 (87.8%) children. Of this group, 54 (16%) cultures were positive but 43 (13%) samples yielded contaminants (including 29 isolates of coagulase negative Staphylococci); a clinically significant organism was isolated from 11 (3.3%) of blood cultures (five We screened 342/385 (89%) children for HIV of whom 38 (11.1%) were positive on rapid antibody test – five aged above 18 months and 33 below 18 months (median age 5.4 months). Confirmatory PCR testing for HIV diagnosis was done in 32/33 rapid antibody positive children aged below 18 months (one patient died before a PCR was obtained). HIV prevalence in the study population was 10.6% (37/341) and varied between subgroups – 8.2% (13/159) in children with SP and 12.6% (23/182) in those with VSP.We conducted a comprehensive audit at KNH to determine the clinical effectiveness of WHO case management guidelines for children admitted with community-acquired SP or VSP. The population studied was drawn from the Kenyan National Hospital, and among admitted children, 46% had SP and 54% VSP. This contrasts with a recent report from a Kenyan district hospital reporting a ratio of 3:1 for SP:VSP  compares with the 13.6% TF rate  reported in a multi-country trial of 958 predominantly Asian children in which recruitment at the Zambian site was stopped owing to high mortality  in some children meeting WHO criteria for VSP and possible over-treatment in some  meeting criteria for SP. Difficulty in ensuring compliance with guidelines is well-recognised  provided power to detect odds ratios >2 for risk factors with a prevalence of 20%. Whereas there was an effort to screen all children for eligibility, 106 children  were admitted with pneumonia and not studied. Demographical and outcome data for these children collected retrospectively were found to be comparable to those of the patients enrolled (data not shown). The failure to recruit all potentially eligible children was commonly because recruiting investigators (paediatric trainees) had continuing commitments to routine care and there were inadequate funds for additional dedicated research staff.While TF is frequently used as a measure of outcome in clinical studies, we found that the rate differs greatly depending on the definition used. This was particularly so in children with SP in whom there was a tendency to revise management in the absence of any apparent supportive clinical, laboratory or radiological evidence. There is a clear difference between populations of children with carefully classified SP and VSP, with relatively low rates of TF and mortality in children with the former. These findings offer some support to current recommendations for monotherapy in the treatment of SP but further data, with better enforcement of guideline-directed therapy are required. Further, our study revealed no difference in clinical outcomes among children treated with standard treatments and those perceived to be more effective; however, the appropriate studies to address clinical questions of this nature would be locally conducted randomized controlled trials which are currently poorly supported. Building capacity for measuring treatment effectiveness and the conduct of trials is urgently needed if global targets for reduction in childhood pneumonia mortality are to be met.


One of the funding sources was omitted from the Acknowledgments list. The corrected list is as follows. This work was supported by the Brazilian organizations Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) 2011/18038-9, Rede Nacional de Métodos Alternativos—Conselho Nacional de Desenvolvimento Científico e Tecnológico (RENAMA-CNPq) 403586/2012-7 and Programa de Apoio ao Desenvolvimento Científico da Faculdade de Ciências Farmacêuticas da UNESP (PADC/FCF). We thank Daniella Sayuri Yamazaki for support with the animal experiment and Dr. Isabel Cristiane da Silva for all the support with A549 pneumocytes culture.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To validate a Spanish version of the Test of Gross Motor Development (TGMD-2) for the Chilean population. Descriptive, transversal, non-experimental validity and reliability study. Four translators, three experts and 92 Chilean children, from five to 10 years, students from a primary school in Santiago, Chile, have participated. The Committee of Experts has carried out translation, back-translation and revision processes to determine the translinguistic equivalence and content validity of the test, using the content validity index in 2013. In addition, a pilot implementation was achieved to determine test reliability in Spanish, by using the intraclass correlation coefficient and Bland-Altman method. We evaluated whether the results presented significant differences by replacing the bat with a racket, using T-test. We obtained a content validity index higher than 0.80 for language clarity and relevance of the TGMD-2 for children. There were significant differences in the object control subtest when comparing the results with bat and racket. The intraclass correlation coefficient for reliability inter-rater, intra-rater and test-retest reliability was greater than 0.80 in all cases. The TGMD-2 has appropriate content validity to be applied in the Chilean population. The reliability of this test is within the appropriate parameters and its use could be recommended in this population after the establishment of normative data, setting a further precedent for the validation in other Latin American countries. International evidence points out to positive aspects on mastering mature motor patterns, which will contribute to physical, cognitive and social development.Chile is a country with high prevalence of childhood obesity, sedentary lifestyle, and cardiovascular diseases.,,One of the most used tools in the international literature is the Test of Gross Motor Development version 2 (TGMD-2), designed by Dale Ulrich, in the United States. This tool aims to identify children with deficits in gross motor development, from three to 10 years of age, evaluating 12 BMS grouped in two subtests: one of locomotor skills and other of object control skills. It is a test focused on the process and on the quality of the movement of a particular BMS. It enables to compare the performance of each individual with pre-established movement quality criteria, or with regulatory results of a representative and statistical sample of the population on which the test is validated.It is interesting to investigate the reproducibility of the test in other countries, since it was designed in a specific context. For example, the batting test is considered an important skill for pre-sports development of American boys and girls. However, in Chile and most countries in Latin America, it is not a widely practiced skill.The purpose of this study was to validate a version in Spanish of the test of gross motor development (TGMD-2) for the Chilean population.This is a descriptive study, part of the validation process of the gross motor instrument, TGMD-2. The study was conducted in three phases. The first consisted of a process of translation and back-translation to obtain a version of the TGMD-2 with translinguistic equivalence to the original test. The second was a content validation. Finally, the third one was an assessment of the inter-rater and intra-rater reliability of the test in Spanish, in addition to test-retest with the purpose of establishing the time stability of the data.The TGMD-2 was translated from English into Spanish independently by two translators whose native language is Spanish. Two versions of the test were created, which were contrasted by a bilingual investigator to obtain a preliminary version in Spanish. This preliminary version was subjected to a blind and independent back-translation by other two translators, who did not know the original test, thus obtaining two versions of the instrument in its original language. A committee was made up of all the translators: two with knowledge in the area of gross motor skills, and two others familiar with colloquial phrases in both languages. This committee compared the back-translated versions with the original test and the preliminary version in Spanish, thus solving, unanimously, semantic discrepancies, and generating a second version in Spanish (TGMD-2-CH).The investigation team decided to evaluate a thirteenth skill based on the controversy surrounding the hitting skill. The bat was replaced by a tennis racket, keeping the evaluation criteria, to know how Chilean children behave in the face of both conditions. Therefore, a modified third version, evaluated in parallel to the TGMD-2-CH, was generated.For content validation, the procedure described by McGartland was conducted.Once approved, the test was applied to the target population to determine its reliability. Data was collected with the TGMD-2-CH already translated into Spanish and approved by experts. Two raters participated, responsible for applying and then independently rate the videos. One of them was responsible for conducting the intra-rater test, while the other was responsible for the test-retest.The reliability study was conducted in an urban area in the city of Santiago de Chile. A casual nonprobability sampling was used to select the educational institution. All children between five and 10 years enrolled in the year of 2013 were invited to participate (609 students). Children who refused to participate, or who did not have the consent of their parents (517 children) were excluded from this study. We evaluated 92 children, who were filmed performing the motor skills described in the TGMD-2-CH inside the establishment, during physical education classes, and in the presence of a teacher. Assessments were conducted in groups of three persons according to the test instructions. The recordings were rated by the corresponding rater(s).,,To determine the test-retest reliability, 32 children were randomly selected, who were recorded and evaluated for the second time by the rater, two weeks after the first evaluation. To determine the intra-rater agreement, 32 children were randomly selected, and a rater evaluated on two occasions, with an interval of one month, the same video of these children. These periods were determined based on the existing literature and on protocols used in similar studies. These times are considered as appropriate intervals to minimize possible memory bias of the rater, when evaluating again the same child.versus results using racket; intra-class correlation coefficient (ICC); and the Bland-Altman method for intra-rater, inter-rater and test-retest reliability.,The data was analyzed with the SPSS Program version 20, using measures of central tendency and frequency distribution. In the statistical analysis, we used: the content validity index (CVI); t-test to compare the results of the test using bat This study followed the “International Guidelines for Biomedical Research Involving Human Subjects” from the World Health Organization,We obtained a CVI = 0.88 in the language clarity evaluation of the TGMD-2-CH, and a CVI = 0.83 for the modified TGMD-2. TGMD-2-CH obtained a CVI = 0.90, and the modified test obtained a CVI = 0.84.The TGMD-2-CH and modified TGMD-2 were applied in 92 children between five and 10 years old, with average age of 7.5 years (SD = 1.6 years), 56 boys and 36 girls. Raw scores for each subtest  were calThe Kolmogorov-Smirnov test indicated a normal distribution for the studied variables, for which the t-test was used to determine if there were significant differences between using a bat or a racket. We did not observe any significant differences (p = 0.059) in assessing the total score for both tests. However, we observed statistically significant differences (p = 0.038) when comparing the results of the object control subtest.We randomly selected 32 minors (12 girls) to determine the inter-rater concordance. When analyzing the results of both raters, significant differences between the results of both were obtained (p = 0.006), and a CVI = 0.86 for the total score of the TGMD-2-CH, a CVI = 0.87 for the locomotor subtest, and a CVI = 0.88 for the object control subtest . We obtaWe assessed 38 children randomly (15 girls and 23 boys) to determine the intra-rater concordance. We did not observe any significant differences between the results of both evaluations (p = 0.55). The CVI value for intra-rater concordance of the total score of the GMD-2-CH was 0.91, with CVI = 0.92 for the locomotor subtest and CVI = 0.86 for the object control subtest. For the intra-rater concordance of the modified test, a CVI = 0.93 was obtained for the total score and the object control subtest.We evaluated 32 children (12 girls and 20 boys) to determine test-retest concordance. We did not obtain any significant differences between the results of both evaluations (p = 0.84). The CVI value for the total score of the TGMD-2-CH was 0.88, while for the modified test was 0.90. In the locomotor subtest, the CVI was 0.86; in the object control subtest with bat was 0.80, while with racket was 0.89.Data was distributed homogeneously in the inter-rater, intra-rater and test-retest concordance, concentrating most of them within two standard deviations , 2 and 3,,In the light of the relations established between the mastery of BMS and factors such as cardiorespiratory status, obesity, long term physical activity, academic performance, among others,This study generated a version of the TGMD-2 in Spanish, with high content validity index,Our results are similar to those of Valentini,The inter-rater, intra-rater and test-retest reliability were found to be high according to the values established by Streiner:In the graphic representation using the Bland-Altman method for intra-rater concordance , we coul,,,Although the reliability values obtained are lower than those obtained by Ulrich,The limitations of this study were the sample size, and the age group of the sample, since they constitute only a segment of the target population. The question of what happens to Chilean children from three to four years old remain a pending challenge for further investigations. It is also a challenge to establish in the future normative values for Chilean population, to adjust the raw scores according to age, thus completing the validation process of the TGMD-2-CH. We propose to perform test reliability studies in a representative sample of the Chilean population, to obtain definitive results with reliability values greater than those obtained in this study, and similar to those found in the literature. ,,,La evaluación temprana del desarrollo y habilidades motrices ha cobrado gran importancia recientemente. Existe evidencia internacional que señala los aspectos positivos sobre los cuales repercute dominar patrones motores maduros que contribuirán al desarrollo físico, cognitivo y social.Chile es un país con alta prevalencia de obesidad infantil, sedentarismo y enfermedades cardiovasculares.Test of Gross Motor Development versión 2 (TGMD-2), diseñado por Dale Ulrich, en Estados Unidos. Esta herramienta busca identificar a los niños con déficit en el desarrollo motor grueso, entre los tres y 10 años, evaluando 12 HMB agrupadas en dos subtest: uno de habilidades locomotoras, y otro de habilidades de control de objetos. Es un test enfocado en el proceso y en la calidad del movimiento de una determinada HMB. Permite comparar el desempeño de cada individuo con criterios pre-establecidos, de calidad de movimiento, o con los resultados normativos de una muestra estadística y representativa de la población en la que el test está validado.,,Una de las herramientas más utilizadas en la literatura internacional es el Resulta interesante indagar en la reproductibilidad del test en otros países, ya que este fue diseñado en un contexto determinado. Por ejemplo, la prueba de batear es considerada una habilidad importante para el desarrollo pre-deportivo de los niños y niñas estadounidenses. No obstante, en Chile y en la mayoría de los países en Latinoamérica, esa no es una habilidad ampliamente practicada.El objetivo de este estudio fue validar una versión en español de la prueba de desarrollo motor grueso TGMD-2 para la población chilena.Estudio descriptivo que constituye parte del proceso de validación del instrumento de motricidad gruesa TGMD-2. El estudio se desarrolló en tres fases. La primera constó de un proceso de traducción y retro-traducción para obtener una versión del TGMD-2 con equivalencia translingüística con el test original. La segunda, de una validación de contenido; y la tercera, de una evaluación de la confiabilidad interevaluador e intraevaluador del test en español, además del test re-test, con el objeto de establecer la estabilidad temporal de los datos.El TGMD-2 fue traducido del inglés al español independientemente por dos traductores, cuya lengua nativa es el español. Fueron generadas dos versiones del test, las cuales fueron contrastadas junto a un investigador bilingüe, para obtener una versión preliminar en español. Esta versión preliminar fue sometida a una retro-traducción ciega e independiente por otros dos traductores, quienes no conocían el test original, obteniendo nuevamente dos versiones del instrumento en su lenguaje original. Se conformó un comité con todos los traductores: dos con conocimiento en el área de la motricidad gruesa, y otros dos familiarizados con frases coloquiales de ambos idiomas. Este comité contrastó las versiones retro-traducidas con el test original y con la versión preliminar en español, resolviendo, por unanimidad, discrepancias semánticas, y generando una segunda versión en español (TGMD-2-CH).El equipo de investigación decidió evaluar una decimotercera habilidad, con base en la controversia en torno a la habilidad de batear. Se reemplazó el bate por una raqueta de tenis, manteniendo los criterios de evaluación, para conocer cómo se comportan los niños chilenos frente a ambas condiciones. Por tanto, se generó una tercera versión, modificada, que se evaluó paralelamente al TGMD-2-CH.Para la validación de contenido, se llevó a cabo el procedimiento descrito por McGartland.Una vez aprobado, el test fue aplicado en la población objetivo para determinar su confiabilidad. Los datos fueron recolectados con el test TGMD-2-CH ya traducido al español y aprobado por los expertos. En ella, participaron dos evaluadores, quienes se encargaron de aplicar y luego puntuar independientemente los videos. Uno de ellos se encargó de realizar la prueba de intraevaluador, mientras que el otro, de los test re-test.El estudio de la confiabilidad fue realizado en un sector urbano en la ciudad de Santiago de Chile. Se utilizó un muestreo no probabilístico de tipo causal para seleccionar la institución educativa. Todos los niños entre cinco y 10 años matriculados durante el año 2013 fueron invitados a participar . Fueron excluidos de este estudio los niños que se negaron a participar, o que no tenían el consentimiento de sus apoderados (517 niños). Fueron evaluados 92 niños, quienes fueron filmados realizando las habilidades motoras descritas en el TGMD-2-CH al interior del establecimiento, durante las clases de educación física, y en presencia de un profesor. Las evaluaciones se realizaron en grupos de tres personas, conforme a las indicaciones del test. Las grabaciones fueron calificadas por el o los evaluadores correspondientes.,,Para determinar la confiabilidad test re-test, 32 niños fueron seleccionados al azar, los cuales fueron grabados y evaluados por segunda vez por el evaluador, dos semanas después de la primera evaluación. Para determinar la concordancia intraevaluador, 32 niños fueron seleccionados al azar, y un evaluador calificó en dos oportunidades, con intervalo de un mes, el mismo video de estos niños. Estos periodos fueron determinados con base en la literatura existente y en los protocolos utilizados en estudios similares. Se consideran estos tiempos como intervalos apropiados para minimizar eventual sesgo de memoria del examinador, al evaluar nuevamente al mismo niño.versus los resultados usando raqueta; el coeficiente de correlación intra-clase (ICC); y el método Bland-Altman para la confiabilidad intraevaluador, interevaluador y test re-test.,Los datos fueron analizados con el Programa SPSS versión 20, mediante medidas de tendencia central y distribución de frecuencias. En el análisis estadístico, se utilizó: el índice de validez de contenido (CVI); el t-test para comparar los resultados del test usando bate Este estudio siguió las “Pautas Éticas Internacionales para la Investigación y Experimentación Biomédica en Seres Humanos” de la Organización Mundial de la Salud,Se obtuvo un CVI = 0,88 en la evaluación de la claridad del lenguaje del test TGMD-2-CH, y un CVI = 0,83 para el TGMD-2 modificado. El TGMD-2-CH obtuvo un CVI = 0,90, y el test modificado obtuvo un CVI = 0,84.El TGMD-2-CH y TGMD-2 modificado fueron aplicados en 92 niños entre 5 y 10 años, con media de edad de 7,5 años , 56 hombres y 36 mujeres. Se calcularon los puntajes brutos de cada subtest .La prueba de Kolmogorov-Smirnov indicó una distribución normal para las variables estudiadas, por lo cual se usó la prueba T para determinar si existían diferencias significativas entre usar un bate o una raqueta. No se observaron diferencias significativas  al evaluar el puntaje total de ambas pruebas, No obstante, se observaron diferencias estadísticamente significativas  al comparar los resultados del sub-test de control de objetos.Fueron seleccionados 32 menores (12 niñas) al azar para determinar la concordancia inter-evaluador. Al analizar los resultados de ambos evaluadores, fueron obtenidas diferencias significativas entre los resultados de ambos , y un ICC = 0,86 para el puntaje total del TGMD-2-CH, un ICC = 0,87 para el subtest locomotor, y un ICC = 0,88 para el sub-test de control de objetos . Fueron Fueron evaluados 38 niños al azar (15 niñas y 23 niños) a fin de determinar la concordancia intraevaluador. No fueron obtenidas diferencias significativas entre el resultado de ambas evaluaciones . El valor del ICC para concordancia intraevaluador del puntaje total del TGMD-2-CH fue de 0,91, con ICC = 0,92 para el sub-test locomotor e ICC = 0,86 para el sub-test de control de objetos. Para la concordancia intraevaluador del test modificado, fue obtenido un ICC = 0,93 para el puntaje total y para el sub-test de control de objetos.Fueron evaluados 32 niños (12 niñas y 20 niños) para determinar la concordancia test re-test. No fueron obtenidas diferencias significativas entre los resultados de ambas evaluaciones . El valor del ICC para el puntaje total del TGMD-2-CH fue de 0,88, mientras que para el test modificado fue de 0,90. En el sub-test locomotor, el ICC fue 0,86; en el sub-test de control de objetos con bate fue 0,80, mientras que con raqueta fue 0,89.Existió una distribución homogénea de los datos en la concordancia interevaluador, intraevaluador y test re-test, concentrando la mayoría de ellos dentro de las dos desviaciones estándar , 2 y 3. ,,A la luz de las relaciones establecidas entre el dominio de las HMB y factores como el estado cardio-respiratorio, obesidad, actividad física a largo plazo, y rendimiento académico, entre otros,Este estudio generó una versión del test TGMD-2 en español, con alto índice de validez de contenido,Nuestros resultados son similares con los de Valentini,La confiabilidad interevaluador, intraevaluador y test re-test, resultaron ser altas de acuerdo a los valores establecidos por Streiner:En la representación gráfica utilizando el método Bland-Altman para concordancia intra-evaluador , se pued,,,A pesar de que los valores de confiabilidad obtenidos son menores a los obtenidos por Ulrich,Las limitaciones de este estudio fueron el tamaño muestral, y el rango etario de la muestra utilizada, ya que constituyen solo un segmento de la población objetivo. Queda la interrogante de lo que sucede con los niños chilenos de tres a cuatro años, desafío pendiente para futuras investigaciones. Es también un desafío, establecer en el futuro valores normativos para la población chilena, con el objetivo de ajustar los puntajes brutos según edad, y así concluir el proceso de validación del TGMD-2-CH. Se propone realizar estudios de confiabilidad del test en una muestra representativa de la población chilena, para obtener resultados definitivos, con valores de confiabilidad mayores a los obtenidos en la presente investigación, y similares a los que se han encontrado en la literatura.


There is a spelling error in affiliation 1 for authors Marwan Osman, Dima El Safadi, Amandine Cian, Sadia Benamrouz, Eric Viscogliosi and Gabriela Certad. Affiliation 1 should be: Institut Pasteur de Lille, Centre d’Infection et d’Immunitè de Lille (CIIL), UMR CNRS 8204, Inserm U1019, Université de Lille, Biologie et Diversitè des Pathogènes Eucaryotes Emergents (BDPEE), Lille, France


Lumbar synovial cysts are an uncommon cause of back pain and radiculopathy, usually manifesting with gradual onset of symptoms, secondary to involvement of the spinal canal. Rarely, intracyst hemorrhage occurs, and may acutely present as radicular - or even spinal cord - compression syndrome. Synovial cysts are generally associated with degenerative facets, although the pathogenesis has not been entirely established. We report a case of bleeding complication in a synovial cyst at L2-L3, adjacent to the right interfacet joint, causing acute pain and radiculopathy in a patient on anticoagulation therapy who required surgical resection. Although some cases in cervical and thoracic spine have been reported, most cysts are found in the lumbar region, mainly at L4-L5, given the movement of the lumbar spine is greater and more susceptible to instability.,8Lumbar cysts are generally related to degenerative changes in the facet joint , although their pathogenesis is still controversial.,3-6 For example, a total of 254 cases of spinal synovial cysts were reported in the English language literature, but only eight were associated with bleeding. Intracyst hemorrhage is likely to lead to pronounced compression of nerve roots, explaining the acute symptoms in patients.,9The hemorrhagic variant is rare. Few cases of acute intracyst hemorrhage were described in the literature.We report a case in which hemorrhage of a synovial cyst at L2-L3, adjacent to the right interfacet joint, was responsible for acute back pain and radiculopathy in a patient on anticoagulant treatment, and who required surgical resection.A 67-year-old male patient with mild and chronic back pain, presented with worsening of pain, with initial irradiation to the right lower limb for 2 weeks, without trauma. The patient had a celiac trunk stent placed 4 years earlier due to an aneurysm, and was on oral anticoagulation . The physical examination revealed uncomfortable side movements and rotational movements of the lumbar spine; there was slight hypoesthesia on the dorsal face of both feet and of the first three toes. The magnetic resonance imaging (MRI) of the lumbar spine revealed a large volume intracanal synovial cyst at L2-L3 with hemorrhagic content, causing stenosis of the vertebral canal and compression of the dural sac and of the lateral recess of the right root at L3, in addition to diffuse degenerative spondyloarthropathy . The cys They can be defined as a mass of extradural soft tissue along the medial edge of a degenerated facet joint.Synovial and ganglion cysts are common lesions that typically occur on limbs. On the vertebral spine, they are known as juxtafacet cysts and are considered rare.Synovial cysts are filled with clear or yellowish fluid, have an epithelial lining similar to the synovia, and a demonstrable communication with the joint capsule. If the synovial lining and the joint communication are not evident, the lesion is classified as a ganglion cyst.,2,7,8 Clinical presentation of any juxtafacet cyst depends on the size and location, and on the relation with adjacent structures. There are asymptomatic synovial cysts discovered by chance, as there are also symptomatic ones that cause pain and radiculopathy, generally with chronic development, cauda equina syndrome or, less frequently compressive spinal cord syndrome.,6,7These cysts are usually associated with degenerative disease of the spine, but their etiology may be trauma, inflammatory or congenital.,3-6 Exacerbation of pain may be caused by acute hemorrhage inside the cyst, although it has not been clearly determined if the increased pain is due to expansion of a cyst, leading to radicular compression, or due to inflammation resulting from hemorrhage.,8 Ramieri et al. mentioned that the expansion of the cyst, after hemorrhage is the cause of symptoms, because this occurs even in rare cases of fast growth of the cyst without bleeding. But, in fact, the cause of the acute onset of symptoms in the sudden intracyst hemorrhage is still under debate.Acute onset of neurological deficits and/or symptoms of pain after hemorrhage in lumbar juxtafacet cysts have been reported.,3-6 The high vascularization of the cyst in the presence of micro trauma or spinal instability alone are suggested to be sufficient to originate hemorrhage. There have been reports of intracyst bleeding events with no associated trauma or coagulopathy, suggesting that studies should be stimulated, in order to discover new risk factors involved.,3-5 In our case, it was not possible to definitively correlate the presence of the hemorrhagic cyst with anticoagulation treatment, because the patient was already on acetylsalicylic acid much before the acute onset, and there are no data that show failure in the patient´s coagulation profile nor in platelet function.Some factors have been appointed as predisposing to hemorrhage, such as anticoagulation treatment, trauma, disc herniation, vascular anomaly or still neoangiogenesis on the walls of the cyst, secondary to inflammation.-8Imaging studies of synovial cysts are useful and should be performed for the differential diagnosis with disc herniation, metastases, meningioma, schwannoma, neurofibromas with cystic degeneration, arachnoid, and perineural, dermoid cysts. After an intravenous injection of paramagnetic contrast, enhancement of the cyst wall and of its content and, sometimes, enhancement of the adjacent inter-facet joint have been observed.On T1-weighted MRI sequences, the cysts present as lesions with a low to intermediate signal. At T2, they present high signal content, generally limited by a capsule, which appears as a hypointense line. It should be underscored, however, that, according to the composition of cysts, the intensity of the signal may be heterogeneous, due to the presence of hemorrhage, calcification and gas (vacuum phenomenon). In cysts in which hemorrhage occurs, in the sub-acute phase, metahemoglobin leads to a high signal on all sequences, when compared to non-hemorrhagic cysts. Reduction and/or spontaneous resolution of cysts may occur with rest and immobilization. Non-hemorrhagic synovial cysts are occasionally treated by percutaneous suction with successful resolution of symptoms. Injection of corticoid in the facet joint may be an option. Percutaneous interventions, including cyst suction, injection and/or rupture, are the most non-surgical treatments studied in the literature. Results vary with success rates between 20 to 75% and, in general, approximately 50% of patients reach significant relief until surgical treatment.Treatment of synovial cysts involves both conservative measures, and surgical intervention. The natural history of synovial cysts of the spine is unknown. Certain cases with acute symptoms require emergency surgery. Even when such surgery is performed fast, some patients still remain with a neurological deficit. However, in general, the immediate diagnosis and appropriate surgical approach may attain satisfactory results.,6 Lyons et al. reported the results of 147 patients treated surgically for symptomatic lumbar synovial cysts, and the results at 6 or more months after surgery were from good to excellent in 91%, with most improving motor and sensory functions.Surgical excision with decompression is the definite treatment for lumbar hemorrhagic synovial cysts.Lumbar synovial cysts are a rare, but possible cause, of acute radicular compression, mainly, when they present hemorrhagic complication. Magnetic resonance imaging is the imaging test of choice to diagnose them and exclude other causes. Although percutaneous intervention may be tried, the results vary much. The immediate acknowledgement and appropriate surgical treatment provide, in general, excellent results. -8 Podem ser uma causa de dor lombar e radiculopatia. Embora tenham sido relatados na coluna cervical e torácica, a maioria deles é encontrada na lombar, principalmente em L4-L5, pois a movimentação da coluna lombar é maior e mais suscetível à instabilidade.,8Cistos na coluna vertebral geralmente estão relacionados a alterações degenerativas da faceta articular, embora sua patogênese ainda seja discutível.,3-6 Por exemplo, um total de 254 casos de cistos sinoviais da coluna vertebral foram relatados na literatura inglesa, mas apenas oito foram associados com hemorragia. É provável que o sangramento intracístico conduza à compressão acentuada das raízes dos nervos, justificando a sintomatologia aguda dos pacientes.,9A variante hemorrágica é uma ocorrência rara. Poucos casos de hemorragia aguda intracística têm sido descritos na literatura.Relatamos um caso no qual a hemorragia em um cisto sinovial no nível L2-L3, adjacente à articulação interfacetária direita, foi responsável pelo quadro agudo de lombalgia e radiculopatia num paciente em terapia anticoagulante, sendo necessária a ressecção cirúrgica.stent no tronco celíaco por aneurisma há 4 anos, em uso de anticoagulação oral . Ao exame físico, observou-se desconforto aos movimentos de lateralização e de rotação da coluna lombar; havia discreta hipoestesia na face dorsal de ambos os pés e dos três primeiros dedos. Ressonância magnética (RM) da coluna lombar evidenciou volumoso cisto sinovial intracanal no nível de L2-L3 com conteúdo hemorrágico, determinando estenose do canal vertebral e compressão do saco dural e da raiz direita de L3 no recesso lateral, além de espondiloartropatia degenerativa difusa . Nos cistos em que ocorre hemorragia, na fase subaguda, a meta-hemoglobina leva a um alto sinal em todas as sequências, quando comparados a cistos não hemorrágicos. A redução e/ou resolução espontânea dos cistos pode ocorrer com repouso e imobilização. Cistos sinoviais não hemorrágicos ocasionalmente são tratados por aspiração percutânea com resolução bem-sucedida dos sintomas. A injeção de corticóide na articulação facetária pode ser uma opção. Intervenções percutâneas, incluindo aspiração do cisto, injeção e/ou ruptura, são os tratamentos não cirúrgicos mais estudados na literatura. Seus resultados são variáveis com taxas de sucesso entre 20 a 75% e, em geral, aproximadamente 50% dos pacientes alcançam um alívio significativo até o tratamento cirúrgico.O tratamento para cistos sinoviais envolve tanto medidas conservadoras, quanto intervenção cirúrgica. A história natural de cistos sinoviais da coluna é desconhecida. Certos casos com sintomas agudos requerem cirurgia de emergência. Mesmo quando tal cirurgia é realizada rapidamente, alguns pacientes ainda permanecem com déficit neurológico. No entanto, em geral, o diagnóstico imediato e a abordagem cirúrgica adequada podem produzir bons resultados.,6 Lyons et al. relataram os resultados de 147 pacientes tratados cirurgicamente para cistos sinoviais lombares sintomáticos, e os resultados de 6 meses ou mais após a cirurgia foram de bom a excelente em 91%, com a maioria melhorando as funções motora e sensorial.Excisão cirúrgica com descompressão é o tratamento definitivo para cistos sinoviais hemorrágicos lombares.Os cistos sinoviais lombares são uma causa rara, mas possível, de compressão radicular aguda, principalmente, quando apresentam complicação hemorrágica. A ressonância magnética é o exame de imagem de escolha para diagnosticá-los e excluir outras causas. Embora a intervenção percutânea possa ser tentada, os resultados são bastante variáveis. O reconhecimento imediato e o tratamento cirúrgico adequado proporcionam, em geral, um excelente resultado.