Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection / 中国实验方剂学杂志

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Comparison of two pandemics: H1N1 and SARS-CoV-2

SUMMARY OBJECTIVE: We aimed to compare the clinical, epidemiological, and prognostic features of the H1N1 pandemic in 2009 and the severe acute respiratory syndrome coronavirus 2 pandemic in 2020. METHODS: This retrospective study involved subjects from seven centers that were admitted and found to be positive for H1N1 or COVID-19 real-time polymerase chain reaction test. RESULTS: A total of 143 patients with H1N1 and 309 patients with COVID-19 were involved in the study. H1N1 patients were younger than COVID-19 ones. While 58.7% of H1N1 patients were female, 57.9% of COVID-19 patients were male. Complaints of fever, cough, sputum, sore throat, myalgia, weakness, headache, and shortness of breath in H1N1 patients were statistically higher than in COVID-19 ones. The duration of symptoms until H1N1 patients were admitted to the hospital was shorter than that for COVID-19 patients. Leukopenia was more common in COVID-19 patients. C-reactive protein levels were higher in COVID-19 patients, while lactate dehydrogenase levels were higher in H1N1 ones. The mortality rate was also higher in H1N1 cases. CONCLUSIONS: The severe acute respiratory syndrome coronavirus 2 pandemic is a major public health problem that continues to affect the world with its high rate of contagion. In addition, no vaccines or a specific drug for the benefit of millions of people have been found yet. The H1N1 pandemic is an epidemic that affected the whole world about ten years ago and was prevented by the development of vaccines at a short period. Experience in the H1N1 pandemic may be the guide to prevent the COVID-19 pandemic from a worse end.

As Repercussões Históricas da Pandemia da Gripe Influenza A (H1N1) no Brasil / Las Repercusiones Históricas de la Pandemia de Gripe de la Influenza a (h1n1) de Brasil / The Historical Repercussions of the Influenza Pandemic a (h1n1) in Brazil

Introdução: A pandemia da gripe influenza A (H1N1) ocorrida em 2009 foi considerada a primeira do Século XXI com importantes consequências para a saúde pública mundial. Objetivo: Analisar as repercussões da pandemia da gripe influenza A (H1N1) no Brasil. Método: Trata-se de um estudo histórico-social, cujas fontes diretas utilizadas foram documentos escritos. Discussão e Resultados: As estratégias empreendidas evidenciadas foram implementadas pelo Ministério da Saúde para conter o avanço da doença no país. Entre essas a Carta Aberta, a Nota Técnica sobre Emergência de Saúde Pública de Importância Internacional e o Plano Brasileiro de Preparação para Enfrentamento de uma Pandemia de Influenza. Considerações Finais: Evidenciamos que as autoridades de saúde investiram na luta contra a pandemia no contexto das recomendações da Organização Mundial da Saúde e das demandas de saúde da população brasileira frente aos desafios provocados pela gripe influenza A (H1N1).

Introduction: The Influenza Pandemic type A(H1N1), which occured in 2009, was considered the first of the twenty-first century with important consequences for all the public health systems around the world. Objective: To analyze the implications of the influenza pandemic A H1N1 on the public health system in Brazil. Method: qualitative research, with a socio-historical approach based on direct sources which consisted of written documents. Discussion and Results: The evidenced strategies were implemented by the Ministry of Health to contain the progress of the disease in the country. Among these strategies were an Open Letter, a Technical Note on Public Health Emergency of International Concern e and the Brazilian Preparation Plan for Coping with Pandemic Influenza. Final Considerations: It has been demonstrated that the Health Authorities invested in the fight against the Pandemic, meeting the recommendations of the World Health Organization as well as the health demands of the Brazilian population in the face of the challenges which the H1N1 epidemic represented.

Introducción: La Pandemia de Influenza tipo A (H1N1) ocurrió en 2009, fue considerada la primera del Siglo XXI con importantes consecuencias para la salud pública mundial. Objetivo: Analizar las implicaciones de la pandemia de gripe influenza A H1N1 en Brasil. Método: Investigación cualitativa, con abordaje histórico-social, dónde utilizaron como fuentes directas documentos escritos. Discusión Resultados: El Ministerio de la Salud implementó las estrategias emprendidas evidenciadas para contener el progreso de la enfermedad en el país. Entre ellas está la Carta Abierta, la Nota Técnica sobre Emergencia de Salud Pública de Importancia Internacional y el Plan Brasileño para el Enfrentamiento de una Pandemia de Influenza. Consideraciones finales: Podemos evidenciar que las autoridades de salud invirtieron en la lucha contra la Pandemia estando en concordancia con las ecomendaciones de la Organización Mundial de la Salud y de las demandas de salud de la población brasileña frente a los desafíos que impuso la epidemia H1N1.

H1N1: perfil clínico-epidemiológico de pacientes atendidos em um hospital / H1N1: clinical and epidemiological profile of patients treated in a hospital

Objetivo: Avaliar casos de suspeita de gripe H1N1, bem como comparar aspectos epidemiológicos e clínicos dos pacientes com gripe H1N1 confirmada em relação àqueles não confirmados; analisar os critérios de gravidade clínica com relação à confirmação (ou não) da gripe H1N1 e seu desfecho (mortalidade); e criar um banco de dados para fins de comparação com a literatura nacional e mundial. Métodos: Estudo retrospectivo de coorte transversal realizado no período sazonal (outono e inverno) no ano de 2016. Foram analisados os prontuários, acessíveis e completos, de pacientes com suspeita clínica de H1N1, além daqueles com resultados definidos na sorologia. A partir dos dados coletados, foi elaborada tabela de análise epidemiológica, com informações clínicas, laboratoriais e sorológicas. Resultados: Destacam-se a média das faixas etárias mais acometidas de 48 anos, além dos sintomas mais comuns que foram dispneia, tosse e mialgia; as comorbidades foram hipertensão arterial sistêmica, cardiopatias, diabetes e doença pulmonar obstrutiva crônica. Conclusão: Este trabalho contribuiu com a caracterização do perfil epidemiológico regional e auxiliou na definição de indicadores de diagnóstico e gravidade, além de agregar à literatura conteúdos de caráter relevante. Este estudo está registrado como CAAE 58664016.2.0000.5515 na Plataforma Brasil. (AU)

Objective: To evaluate cases of suspected H1N1 flu, as well as to compare epidemiological and clinical aspects of patients with confirmed H1N1 influenza to those who were not confirmed; to analyze the criteria of clinical severity regarding the confirmation (or not) of H1N1 influenza, and its outcome (mortality); and to create a database to be compared with the national and world literature. Methods: This is a cross-sectional retrospective cohort study, carried out in the seasonal period ( fall/winter) of 2016. Accessible and complete medical records of patients with clinical suspicion of H1N1 were analyzed along with those with defined serology results. Based on the collected data, a table of epidemiological analysis was elaborated with clinical, laboratory and serological information. Results: The mean age of the most affected age groups was 48 years; the most common symptoms were dyspnea, cough and myalgia; and the comorbidities were systemic arterial hypertension, cardiopathies, diabetes, and chronic obstructive pulmonary disease. Conclusion: This work contributed to the characterization of the regional epidemiological profile, and helped in the definition of indicators of diagnosis and severity, besides adding relevant content to the literature. This study is registered as CAAE 58664016.2.0000.5515 at Plataforma Brasil. (AU)

Uso da ventilação não invasiva na SDRA e pneumonia secundária a H1N1: revisão sistemática / Use of non-invasive ventilation in ARDS and secondary pneumonia H1N1: systematic review

INTRODUÇÃO: A influenza A é uma infecção respiratória aguda, associada a epidemias e pandemias, sendo um vírus de comportamento sazonal. O uso precoce da ventilação não invasiva tem se mostrado um tratamento de primeira linha em pacientes com síndrome do desconforto respiratório e pneumonia secundaria a influenza A H1N1, resultando em menores taxas de mortalidade. OBJETIVO: Investigar através de revisão sistemática o uso da ventilação não invasiva em pacientes diagnosticados com Influenza A H1N1, secundário a pneumonia e a síndrome do desconforto respiratório agudo. MATERIAIS E MÉTODOS: Foram realizadas buscas nas bases de dados do Periódicos Capes, Science Direct, SciELO, e Pubmed, selecionandose os estudos desenvolvidos nos últimos 10 anos, não sendo imposta restrição de idiomas para a pesquisa. A qualidade metodológica dos estudos foi apontada utilizando a escala de PEDro. RESULTADOS: 16 estudos preencheram o critério de elegibilidade e foram incluídos neste estudo segundo escore de PEDro. Nove estudos mostraram que o uso da ventilação não invasiva foi eficiente em pacientes de média e baixa hipoxemia, diminuindo a taxa de intubação orotraqueal e doenças associadas, menor permanência hospitalar e menores taxas de mortalidade. CONCLUSÃO: O uso da VNI em pacientes com Síndrome do Desconforto Respiratório Agudo e pneumonia secundária ao vírus influenza A H1N1 mostrou-se relevante na reversão da hipoxemia moderada e leve. Critérios, parâmetros e protocolos bem estabelecidos, torna-se muito útil, juntamente com profissionais experientes e preparados, visando assim uma menor taxa de intubação orotraqueal e doenças associadas, e consequentemente uma menor permanência hospitalar e menores taxas de mortalidade.

INTRODUCTION: Influenza A is an acute respiratory infection, associated with epidemics and pandemics, being a virus with seasonal behavior. Early use of noninvasive ventilation has been shown to be first-line treatment in patients with respiratory distress syndrome and influenza A H1N1 secondary pneumonia, resulting in lower mortality rates. OBJECTIVE: To investigate through a systematic review the use of noninvasive ventilation in patients diagnosed with influenza A H1N1, secondary to pneumonia and acute respiratory distress syndrome. MATERIALS AND METHODS: Searches were carried out in the Capes, Science Direct, SciELO, and Pubmed journals, selecting the studies developed in the last 10 years, with no language restriction for the research. The methodological quality of the studies was indicated using the PEDro scale. RESULTS: 16 studies met the eligibility criteria and were included in this study according to PEDro score. Where 9 studies showed that the use of noninvasive ventilation was efficient in patients with medium and low hypoxemia, decreasing the rate of orotracheal intubation and associated diseases, shorter hospital stay and lower mortality rates. CONCLUSION: The use of NIV in patients with Acute Respiratory Distress Syndrome and influenza A H1N1 secondary pneumonia has been shown to be relevant for reversing moderate and mild hypoxemia. Well-established criteria, parameters and protocols become very useful, along with experienced and prepared professionals, thus aiming at a lower rate of orotracheal intubation and associated diseases, and consequently a shorter hospital stay and lower mortality rates.

Initial chest X-ray findings in pediatric patients diagnosed with H1N1 virus infection / Achados iniciais na radiografia de tórax em uma população pediátrica com diagnóstico de infecção viral por H1N1

Abstract Objective: To evaluate chest X-ray findings in pediatric patients diagnosed with influenza A (H1N1) virus infection. Materials and Methods: We retrospectively reviewed chest X-ray findings in 17 cases of pulmonary infection with the H1N1 virus (in 7 males and 10 females) examined between 2012 and 2016. The mean age of the patients was 14 months (range, 2-89 months). The diagnosis was established on the basis of clinical and radiographic criteria, and the virus was detected by polymerase chain reaction. The radiographic findings were categorized by type/pattern of opacity and by lung zone. The patients were divided into two groups: those not requiring ventilatory support; and those requiring ventilatory support or evolving to death. Results: The abnormality most often seen on chest X-rays was that of peribronchovascular opacities, the majority of which affected less than 25% of the lung, the involvement being bilateral and asymmetric. The lung zone most frequently involved was the middle third, with central and peripheral distribution, without pleural effusion. There was a statistically significant difference between the groups in terms of the symmetry of pulmonary involvement, asymmetric findings predominating in the group that required ventilatory support (p = 0.029). Conclusion: In pediatric patients with H1N1 virus infection, the main alterations on the initial chest X-rays are peribronchovascular opacities, nonspecific alveolar opacities, and consolidations. Although the definitive diagnosis of H1N1 virus infection cannot be made on the basis of imaging characteristics alone, using a combination of clinical and radiographic findings can substantially improve the diagnostic accuracy.

Resumo Objetivo: Avaliar os achados na radiografia de tórax de pacientes com diagnóstico de infecção pelo vírus influenza. Materiais e Métodos: Revisamos, retrospectivamente, os achados na radiografia de tórax de 17 casos de infecção pulmonar pelo vírus influenza (7 do sexo masculino e 10 do sexo feminino; idade média de 14 meses, variação de 2 a 89 meses). Os pacientes foram examinados entre 2012 e 2016 e o diagnóstico foi estabelecido por critérios clinicorradiológicos e detecção do vírus por reação em cadeia de polimerase. Os achados radiológicos foram caracterizados por tipo e padrão de opacidade e distribuição por zonas pulmonares. A população estudada foi dividida em dois grupos: sem suporte ventilatório e com suporte ventilatório e/ou óbito. Resultados: A anormalidade encontrada com maior frequência na radiografia de tórax foram as marcas peribroncovasculares, a maioria delas com extensão menor de 25% do pulmão, envolvimento bilateral e assimétrico. A região mais frequentemente envolvida foi o terço médio, com distribuição central e periférica e ausência de derrame pleural. Houve diferença estatisticamente significante na simetria do envolvimento pulmonar, entre os grupos, havendo preponderância de achado assimétrico (p = 0,029) no grupo que necessitou de suporte ventilatório. Conclusão: Pacientes pediátricos com infecção pelo H1N1 apresentam como alterações principais na radiografia do tórax inicial marcas peribroncovasculares, opacidades alveolares inespecíficas e consolidações. Embora o diagnóstico definitivo não possa ser feito com base em imagens características isoladas, uma combinação dos achados clínicos e radiográficos pode melhorar substancialmente a acurácia do diagnóstico nessa doença.

Interesting post-mortem findings in a H1N1 influenza-positive pneumonia patient

Reports of histopathological findings in a patient infected with H1N1 influenza virus are limited in the literature, although many deaths have occurred because of this viral infection. In an otherwise healthy individual with no underlying co-morbid conditions, this virus passes off as a very mild disease. However, it can be fatal in the presence of underlying risk factors. Here, we present the autopsy findings of a patient who died of H1N1 infection, but who was apparently healthy with no predisposing ailments. The autopsy revealed chronic kidney disease and caseating granulomatous lymphadenitis in addition to the known classical diffuse alveolar damage picture seen in this condition. These underlying co-morbidities may provide greater insight and a better understanding of this infection.

Fatores associados ao óbito dos casos graves de influenza A(H1N1)pdm09 / Factors associated with death of severe cases of influenza A(H1N1)pdm09

Resumo Introdução A primeira pandemia de influenza do século XXI ocorreu em 2009, causada pelo novo subtipo de vírus da gripe, o vírus influenza A(H1N1)pdm09. Objetivo Analisar os fatores associados ao óbito por Síndrome Respiratória Aguda Grave (SRAG) por influenza A(H1N1)pdm09 em residentes do município do Rio de Janeiro. Método Análise de dados secundários, incluindo 1.191 casos confirmados para influenza A(H1N1) com critério clínico para SRAG, residentes no município do Rio de Janeiro, em 2009. Análise estatística descritiva e regressão logística para estudo dos fatores associados ao óbito. Resultados 60,3% ocorreram em mulheres, sendo 185 gestantes; 48,1% em menores de 20 anos; 35,7% tinham comorbidades; 91,4% foram hospitalizados; 7,4% foram a óbito. Observou-se maior chance de óbito associada à baixa escolaridade, à presença de comorbidade, ao padrão radiológico de infiltrado intersticial, consolidação ou misto, à confirmação laboratorial e ao estado vacinal contra gripe ignorado. Conclusão Indivíduos com baixa escolaridade, com pelo menos uma comorbidade e com comprometimento pulmonar com um padrão radiológico com infiltrado intersticial, consolidação ou misto tiveram maior chance de evolução a óbito. O melhor conhecimento desse perfil permite um planejamento mais eficiente da assistência à saúde dos pacientes.

Abstract Introduction the first influenza pandemic of the 21st century occurred in 2009, caused by the new subtype of influenza virus, influenza A (H1N1) pdm09. Objective to analyze the factors associated with death due to Severe Acute Respiratory Infection (SARI) caused by influenza A (H1N1) pdm09 in residents of the city of Rio de Janeiro. Method Analysis of secondary data, including 1,191 confirmed cases of influenza A (H1N1) pdm09 with clinical criteria for SARI, residents of the city of Rio de Janeiro, in 2009. Descriptive statistical analysis and logistic regression for the study of factors associated with death. Results 60.3% occurred in women, with 185 pregnant women; 48.1% in children under 20 years old; 35.7% had comorbidities; 91.4% were hospitalized, and 7.4% died. There was a higher chance of death associated with low educational level, presence of comorbidity, radiological pattern of interstitial infiltrate, consolidation or mixed; laboratory confirmation; vaccination status ignored. Conclusion individuals with low educational level who had at least one comorbidity and had pulmonary involvement with a radiological pattern with interstitial infiltrate, consolidation or mixed had a higher chance of dying. Knowledge of this profile allows for more efficient planning of health care.

Detection of in vitro Inhibitory Effects of Boehmeria nivea Leaves Extracts on Influenza A Virus （H1N1）and Its Antioxidant Activity / 中国药房

OBJECTIVE： To study the in vitro inhibitory effects and antioxidant activity of different solvent extracts of Boehmeria nivea leaves against influenza A virus（H1N1）， and to expand the medicinal parts of B. nivea and develop natural antiviral and antioxidant drugs. METHODS： The leaves of B. nivea were extracted with 95％ ethanol. The ethanol extract was dissolved by water heating， and extracted with different solvents to obtain petroleum ether phase， trichloromethane phase， ethyl acetate phase， n-butanol phase and aqueous phase extracts of B. nivea leaves. The toxicity of aqueous extract of B. nivea leaves （50-400 μg/mL） on Madin-Darby canine kidney （MDCK） cell line was investigated. Using ribavirin as positive control， MDCK cells were attacked by influenza A virus（H1N1）. Western blotting assay was used to detect the expression of nucleoproteins （NP） in viral infected cells after treated with same concentrations of petroleum ether phase， trichloromethane phase， ethyl acetate phase， n-butanol phase and aqueous phase extracts of B. nivea leaves （100 μg/mL）， different concentrations of aqueous phase extract solution of B. nivea leaves （50， 100， 200， 400 μg/mL） and different concentrations of ribavirin solution （0.31， 0.63， 1.25 μg/mL）. Using vitamin C as a positive control， hydroxyl radical（·OH） scavenging test， DPPH radical scavenging test and reduction test were used to investigate in vitro antioxidant activity of the extracts. RESULTS： Aqueous phase extract of B. nivea leaves with concentration less than 400 μg/mL was nontoxic to MDCK cells. The petroleum ether phase， trichloromethane phase， ethyl acetate phase and aqueous phase extracts at 100 g/mL could significantly reduce the expression of NP protein in influenza A virus（H1N1） infected cells （P＜0.01）. Different concentrations （50-400 μg/mL） of aqueous extract could significantly reduce the protein expression of NP （P＜0.01） in concentration-dependent manner. The in vitro antioxidant activity of petroleum ether phase and ethyl acetate phase was similar to that of vitamin C. CONCLUSIONS： B. nivea leaves extract have better anti-influenza A virus（H1N1） effects in vitro， and the extracts of petroleum ether phase and ethyl acetate phase show good antioxidant activity in vitro.

Clinical analysis of seven cases of H1N1 influenza-associated encephalopathy in children / 中华儿科杂志

Objective@#To investigate the clinical manifestations, diagnosis, and treatment of H1N1 influenza A-associated encephalopathy (IAE) in children.@*Methods@#The clinical manifestations, laboratory tests, cranial magnetic resonance imaging (MRI), electroencephalography (EEG) examinations and treatments of seven children with H1N1 IAE hospitalized in Guangzhou Women and Children′s Medical Center from December 2018 to January 2019 were retrospectively analyzed.@*Results@#Five of the seven children with H1N1 IAE were female. The age at admission was 4 years and 5 months (range 7 months-9 years). Neurological symptoms occurred simultaneously or early (0-3 days) after the flu-like symptom appeared. The main clinical manifestations of neurological symptoms were seizures (repeated seizures in five cases and status convulsion in two cases, including one case of unexpected fever and repeated seizures in a nine-year old girl) accompanied with altered consciousness (drowsiness in five cases and coma in two cases). Cranial MRI in three cases displayed multifocal lesions, mainly in the bilateral thalamus, brainstem and cerebellar hemisphere. MRI also showed reversible splenial lesion in the corpus callusumin in three cases. EEG tracings were characterized by diffuse slow wave activity in four cases, and status epilepticus was monitored in one case. All the 7 cases were treated with oral oseltamivir. Three cases were treated with pulsed methylprednisolone and intravenous immunoglobulin. One case was treated with intravenous immunoglobulin alone and all the patients received oral oseltamivir. All the patients survived, with three patients had minor neurological sequelae at discharge.@*Conclusions@#The main clinical manifestations of H1N1 IAE are seizures and altered consciousness. Cranial MRI combined with EEG is helpful for early diagnosis. Intravenous immunoglobulin and (or) methylprednisolone should be considered for severe cases.

A case report of H1N1 severe pneumonia treated with mechanical ventilation in the prone position / 天津医药

@#Acute respiratory distress syndrome (ARDS) is an acute respiratory failure characterized by progressive respiratory dyspnea and intractable hypoxemia caused by various causes both inside and outside the lungs. At present, there is still controversy about the monitoring of prone position（PP）ventilation in patients with severe hypoxemia. This article summarized a case of severe ARDS with type A H1N1 severe pneumonia treated with PP ventilation to improve oxygenation, so as to provide reference for clinical treatment.

Construction of a Transcriptome-Driven Network at the Early Stage of Infection with Influenza A H1N1 in Human Lung Alveolar Epithelial Cells

We aimed to understand the molecular changes in host cells that accompany infection by the seasonal influenza A H1N1 virus because the initial response rapidly changes owing to the fact that the virus has a robust initial propagation phase. Human epithelial alveolar A549 cells were infected and total RNA was extracted at 30 min, 1 h, 2 h, 4 h, 8 h, 24 h, and 48 h post infection (h.p.i.). The differentially expressed host genes were clustered into two distinct sets of genes as the infection progressed over time. The patterns of expression were significantly different at the early stages of infection. One of the responses showed roles similar to those associated with the enrichment gene sets to known ‘gp120 pathway in HIV.’ This gene set contains genes known to play roles in preventing the progress of apoptosis, which infected cells undergo as a response to viral infection. The other gene set showed enrichment of ‘Drug Metabolism Enzymes (DMEs).’ The identification of two distinct gene sets indicates that the virus regulates the cell's mechanisms to create a favorable environment for its stable replication and protection of gene metabolites within 8 h.

Oxigenação por membrana extracorpórea na síndrome do desconforto respiratório agudo devido à pneumonia por influenza A (H1N1) pdm09. Experiência em um único centro durante a temporada de 2013-2014 / Extracorporeal membrane oxygenation in acute respiratory distress syndrome due to influenza A (H1N1)pdm09 pneumonia. A single-center experience during the 2013-2014 season

RESUMO Objetivo: Descrever os desfechos de pacientes com síndrome do desconforto respiratório agudo associada à influenza subtipo H1N1 grave tratados com oxigenação por membrana extracorpórea. Métodos: Trata-se de revisão retrospectiva de uma coorte de pacientes oriunda de um único centro, constituída por adultos com síndrome do desconforto respiratório agudo relacionada com influenza subtipo H1N1 e tratados com oxigenação venovenosa por membrana extracorpórea durante a temporada de inverno no hemisfério norte de 2013/2014. Resultados: Dez pacientes receberam oxigenação venovenosa por membrana extracorpórea para tratamento de influenza subtipo H1N1 entre janeiro de 2013 e março de 2014. Sete deles foram transferidos para nosso centro visando à utilização de oxigenação por membrana extracorpórea dentro de um período de 72 horas após o início da ventilação mecânica. A idade mediana foi de 40 anos, sendo 30% dos pacientes do sexo feminino. O valor mediano da proporção entre pressão parcial de oxigênio e fração inspirada de oxigênio foi de 62,5, sendo o escore RESP mediano de 6. Três pacientes receberam inalação de óxido nítrico e quatro utilizaram posição prona como tratamento de resgate antes de ser iniciada a oxigenação por membrana extracorpórea. A duração mediana da ventilação mecânica foi de 22 dias (variação de 14 - 32). O tempo mediano de permanência na unidade de terapia intensiva foi de 27 dias (variação de 14 - 39). O tempo mediano de permanência no hospital foi de 29,1 dias (variação de 16,0 - 46,9). Ocorreram complicações não importantes de sangramento em seis dos dez pacientes. Oito dos dez pacientes sobreviveram até a alta hospitalar. Conclusão: Os sobreviventes eram relativamente jovens e tiveram alta com boas condições funcionais, o que salienta os anos de vida ajustados pela qualidade que foram salvos. Nossa experiência demonstra que mesmo um programa ainda relativamente novo de oxigenação por membrana extracorpórea pode desempenhar um papel importante, e proporcionar resultados excelentes para os pacientes mais graves.

ABSTRACT Objective: This report aimed to describe the outcomes of the patients with severe H1N1 associated acute respiratory distress syndrome who were treated with extracorporeal membrane oxygenation therapy. Methods: This retrospective review analyzed a single-center cohort of adult patients with H1N1-related acute respiratory distress syndrome who were managed with veno-venous extracorporeal membrane oxygenation during the winter of 2013/2014. Results: A total of 10 patients received veno-venous extracorporeal membrane oxygenation for H1N1 influenza between January 2013 and March 2014. Seven patients were transferred to our center for extracorporeal membrane oxygenation consideration (all within 72 hours of initiating mechanical ventilation). The median patient age was forty years, and 30% were female. The median arterial oxygen partial pressure to fraction of inspired oxygen ratio was 62.5, and the median RESP score was 6. Three patients received inhaled nitric oxide, and four patients were proned as rescue therapy before extracorporeal membrane oxygenation was initiated. The median duration of mechanical ventilation was twenty-two days (range, 14 - 32). The median length of stay in the intensive care unit was twenty-seven days (range, 14 - 39). The median hospital length of stay was 29.1 days (range, 16.0 - 46.9). Minor bleeding complications occurred in 6 of 10 patients. Eight of the ten patients survived to hospital discharge. Conclusion: The survivors were relatively young and discharged with good functional status (i.e., enhancing quality-adjusted life-years-saved). Our experience shows that even a relatively new extracorporeal membrane oxygenation program can play an important role in that capacity and provide excellent outcomes for the sickest patients.

Cambios en la presentación clínica de la influenza A H1N1pdm09 después de la pandemia / Changes in the clinical presentation of Influenza A H1N1pdm09 after the pandemic

Background: After the 2009 influenza pandemic the H1N1pdm09 strain circulate seasonally. In 2015, Puerto Montt Hospital in Chile faced a simultaneous outbreak of both seasonal H3N2 and H1N1pdm09 influenza A (IA). Aim: To evaluate the clinical differences between the two viral strains and recent changes in the behavior of H1N1pdm09 IA. Material and Methods: We set up a retrospective study including every adult hospitalized in Puerto Montt Hospital in 2015 due to IA, confirmed by reverse transcription polymerase chain reaction. We compared epidemiological data, clinical presentation, complications, and the outcome of patients with H1N1pdm09 versus those with seasonal influenza. In parallel, we compared 62 cases of thatH1N1 IA from 2015 with 100 cases who were hospitalized and analyzed in 2009. Results: Between July and October 2015, 119 adults with confirmed IA were hospitalized. From 2009 to 2015, the mean age of patients with IAH1N1pdm09 increased from 40.4 ± 17 to 58.8 ± 16 years (p < 0.01). Pneumonia as the cause of hospitalization decreased from 75 to 58% of patients, (p = 0.04). Likewise, the presence of comorbidities increased from 53 to 74%, (p < 0.01). Compared with seasonal H3N2, patients with IAH1N1pdm09 IA were more likely to require intensive care (p < 0.01) and mechanical ventilation (p < 0.01) and developed septic shock (p = 0.03). Their mortality was non-significantly higher (13 and 5% respectively). Conclusions: The clinical presentation of H1N1pdm09 IA has varied over time and now affects an older population, with a greater number of comorbidities. It also appears to be adopting the clinical behavior of a classic seasonal influenza virus.

Detección de virus influenza A, B y subtipos a (H1N1) pdm09, A (H3N2) por múltiple rt-pcr en muestras clínicas / Detection of influenza A, B and subtypes A (H1N1) pdm09, A (H3N2) viruses by multiple qrt-pcr in clinical samples

RESUMEN Objetivos. Estandarizar la técnica de reacción en cadena de la polimerasa en tiempo real (RT-PCR) múltiple para la detección de virus influenza A, B y tipificación de subtipos A (H1N1) pdm09, A (H3N2) en muestras clínicas. Materiales y métodos. Se analizaron 300 muestras de hisopado nasofaríngeo. Esta metodología fue estandarizada en dos pasos: la primera reacción detectó el gen de la matriz del virus de influenza A, gen de la nucleoproteína del virus influenza B y el gen GAPDH de las células huésped. La segunda reacción detectó el gen de la hemaglutinina de los subtipos A (H1N1) pandémico (pdm09) y A (H3N2). Resultados. Se identificaron 109 muestras positivas a influenza A y B, de las cuales 72 fueron positivas a influenza A (36 positivas a influenza A (H1N1) pdm09 y 36 positivos a influenza A (H3N2)) y 37 muestras positivas a influenza B. 191 fueron negativas a ambos virus mediante RT-PCR en tiempo real multiplex. Se encontró una sensibilidad y especificidad del 100% al analizar los resultados de ambas reacciones. El límite de detección viral fue del rango de 7 a 9 copias/µL por virus. Los resultados no mostraron ninguna reacción cruzada con otros virus tales como adenovirus, virus sincitial respiratorio, parainfluenza (1,2 y 3), metapneumovirus, subtipos A (H1N1) estacional, A (H5N2) y VIH. Conclusiones. La RT-PCR múltiple demostró ser una prueba muy sensible y específica para la detección de virus influenza A, B y subtipos A (H1N1, H3N2) y su uso puede ser conveniente en brotes estacionales.

ABSTRACT Objectives. To describe the clinical and epidemiological characteristics of patients diagnosed with epidermolysis bullosa (EB) at the Instituto Nacional de Salud (INSN) in Lima, Peru; a National Reference Center for this disease. Material and methods . Observational, descriptive and transversal study. We reviewed the clinical histories and laboratory tests of patients diagnosed with EB treated in INSN from 1993 to 2015. Results. 93 patients were registered. The average age was 7.9 ± 5.6 years; 53.8% (n = 50) were boys. Clinical forms corresponded to dystrophic EB with 41 (44.1%) cases, simple EB with 39 (41.9%) union EB cases with 8 (8.6%) and Kindler syndrome with 4 (4.3%) cases. The clinical form could not be identified in a case. A total of 48 cases (51.6%) came from Lima and Callao, and 45 cases (48.4%) from other provinces of the country. Extracutaneous manifestations involved gastrointestinal (44.1%), ocular (37.6%), odontogenic (87.1%), and nutritional (79.6%) involvement, as well as pseudosindactilia (16.1%). Chronic malnutrition (71.6%), acute malnutrition (17.6%) and anemia (62.4%) were found. Mortality corresponded to 6 cases (6.5%). Conclusions. 93 cases of EB were reported in INSN, the predominant clinical presentation was the dystrophic form.

Glomerulonefritis aguda con requerimiento de diálisis asociada a influenza A H1N1pdm09: comunicación de dos casos / Acute glomerulonephritis with hemodialysis requirement secondary to influenza A H1N1pdm09 infection: report of two cases

Acute renal failure (ARF) requiring hemodialysis is not common among patients affected by influenza. We report two unvaccinated adult patients with smoking habit, which were admitted with severe influenza A H1N1pdm09 that evolved with shock and required mechanical ventilation. Both patients developed progressive renal failure with oliguria/anuria, associated with urinary of inflammatory sediment with proteinuria, microhematuria and in one case also with hypocomplementemia, suggesting acute glomerulonephritis. Renal replacement therapy (RRT) was required in both cases. In one patient, who died of late complications, sequencing of the HA1 segment revealed the previously described D222N mutation associated to severe cases. ARF with RRT appears to be an uncommon complication of patients hospitalized for influenza A H1N1pdm09 and may be secondary to acute glomerulonephritis.

La insuficiencia renal aguda (IRA) que requiere hemodiálisis no es una complicación común entre los pacientes afectados por influenza. Se comunican los casos clínicos de dos pacientes adultos fumadores no vacunados, que se internaron por influenza A H1N1pdm09 grave por shock y necesidad de ventilación mecánica. Ambos desarrollaron una falla renal progresiva con oliguria/anuria, asociada a un sedimento de orina inflamatorio con proteinuria, microhematuria y en un caso además con hipocomplementemia, sugiriendo una glomerulonefritis aguda. Se requirió terapia de reemplazo renal (TRR) en ambos casos. En uno de los pacientes, que falleció por complicaciones tardías, la secuenciación del segmento HA1 reveló la mutación D222N previamente descrita en casos graves. La IRA con TRR parece ser una complicación infrecuente de los pacientes ingresados por influenza A H1N1pdm09 y puede ser secundaria a una glomerulonefritis aguda.

Análise da prevalência de vírus respiratórios em crianças atendidas em um hospital universitário do sul de Minas Gerais / Analysis of respiratory virus prevalence in assisted children in a university hospital of southern of minas gerais

INTRODUÇÃO: As infecções respiratórias virais são doenças de alta incidência no nosso meio. Os vírus circulam durante todo ano, todavia, a incidência destas infeccões aumentam com a sazonalidade. Grande parte destas infecções ocorrem em crianças por serem mais susceptíveis do ponto de vista imunológico. OBJETIVO: Analisar a prevalência dos patógenos virais nas infecções respiratórias em crianças de 0 a 9 anos no Hospital das Clinicas Samuel Libanio(HCSL), Pouso Alegre - MG. MÉTODOS: Foi realizada uma revisão sistemática dos dados coletados a partir de aspirados de orofaringe, para pesquisa de vírus pela equipe da Comissão de Controle de Infecções Hospitalares (CCIH), entre os anos de 2010 e 2014. RESULTADOS: Foram analisados 310 amostras e cerca de 26,4% foram positivas para algum vírus. O vírus sincicial respiratório (VSR) foi o mais prevalente nas crianças menores de um e também na faixa etária de 1 a 4 anos (25,3% e 11,1 %, respectivamente), estatisticamente significante (p<0,001). Já no grupo entre 5 a 9 anos prevaleceu o virus Influenza A H1N1 com 13,8%. CONCLUSÃO: As infecções virais contribuem para um alto número de hospitalizações que oneram o serviço público de saúde, principalmente na faica etária pediátrica. Deste modo, medidas preventiva como campanhas de vacinação devem continuar a ser incentivadas, de preferência abrangendo os vírus mais prevalentes para uma determinada faixa etária. (AU)

Introduction: Viral respiratory infections are of high incidence diseases in our midst. Viruses circulate throughout the year, however, the incidence of these infections increase with seasonality. Most of these infections occur in children because they are more likely immunologically. Objective: To analyze the prevalence of viral pathogens in respiratory infections in children aged 0 to 9 years old at the Samuel Libânio Clinical Hospital, Pouso Alegre-MG. Methods: A systematic review of data collected from aspirates oropharynx was performed to search for viruses by the Commission's Team of Nosocomial Infection Control between the years 2010 and 2014. Results: 310 samples were analyzed and about 26.4% of the samples were positive for a virus. Respiratory syncytial virus (RSV) was the most prevalent in children under one year old and also in the age group 1-4 years (25.3% and 11.1%, respectively), statistically significant (p<0.001). In the group between 5 and 9 years prevailed the virus Influenza A H1N1 with 13.8%. Conclusions: Viral infections contribute to a high number of hospitalizations that burden the public health system, especially in the pediatric age group. Thus, preventive measures such as vaccination campaigns should continue to be encouraged, preferably covering the most prevalent virus for a certain age group (AU)

Study on the Anti-influenza A Virus H1N1 Effect of Aqueous Extraction of Lonicerae Flos in vitro / 中国药房

OBJECTIVE:To investigate the effect of aqueous extraction of Lonicerae Flos (SYHW) on anti-influenza A virus H1N1 (H1N1 virus) in vitro. METHODS:Using Madin-Darby canine kid ney (MDCK) cells cultured in vitro by H1N1 virus, half of the tissue culture infection dose(TCID50)was calculated. Culturing MDCK cells for 24 h with different mass concentrations of SYHW,the maximum non-toxic concentration was investigated. And then test was divided into normal cell group,virus control group,SYHW preventive administration group,therapeutic administration group and direct killing group (given SYHW of maxi-mum non-toxic concentration,infecting cells by 100 TCID50 H1N1 virus),and antiviral effective rate (ER) of SYHW was deter-mined. Test was divided into normal cell group,virus control group,SYHW therapeutic group and direct killing group (the same administration and infection as above),changes of cell proliferation index (PI) and cell apoptosis rate were respectively deter-mined. RESULTS:100 TCID50 of H1N1 virus was 1.26×10-7,and the maximum non-toxic concentration of SYHW on MDCK cells was 50 μg/mL(cell survival rate was 91.3%). ERs of preventive administration group,therapeutic administration group and direct killing group were 0,80.3% and 52.7%,respectively. Compared with normal cell group,PI value in virus control group was sig-nificantly reduced (P<0.05),early and late apoptotic rates were significantly increased (P<0.05). Compared with virus control group,PI value in directly killing group was significantly increased(P<0.05),and early apoptotic rate was significantly reduced (P<0.05);early apoptotic rates in therapeutic administration group were significantly reduced (P<0.05). CONCLUSIONS:SY-HW shows anti-H1N1 virus effect in vitro,therapeutic administration and directly killing are preferred in antiviral effect.

La articulación público-privada en la producción de vacunas en México / Public-private articulation in the production of vaccines in Mexico

RESUMEN El artículo analiza el proceso de privatización de la atención a la salud: la Articulación Público-Privada (APP). Específicamente estudia la producción de vacunas em México, tomando como caso los Laboratorios de Biológicos y Reactivos de México, S.A. de C.V. (Birmex), empresa paraestatal, responsable de producir, distribuir e investigar biológicos y reactivos en México. Interesa destacar el comportamiento de Birmex durante el periodo de la pandemia de influenza de 2009, producida por el virus de la influenza A subtipo H1N1. Los resultados muestran que gracias al impulso de las políticas de liberalización y desregulación, existe una apertura de los servicios públicos a las corporaciones supranacionales.

ABSTRACT This paper analyzes the process of privatization of health care services through the Public-Private Articulation (APA). The production of vaccines in Mexico is studied, through the case study of Biological and Reagents Laboratories of Mexico, LLC (Birmex), company responsible for the production, distribution and investigation of biological and reagents in Mexico. It points out specially Birmex’s performance during the period of pandemic influenza A virus, H1N1 subtype. The results show that there exists opening of the public services to supranational corporations encouraged by policies of liberalization and deregulation.