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.

Diferencias y similitudes clínicas y epidemiológicas de la neumonía viral en dos pandemias

Background: In a decade, we faced two pandemic viruses, influenza A H1N1pdm09 and SARS CoV-2, whose most serious manifestation is pneumonia. Aim: To compare the clinical, epidemiological and management aspects of pneumonias caused by each pandemic virus in adults requiring hospitalization. Material and Methods: Comparative, observational study carried out at a regional Chilean hospital, including 75 patients with influenza A H1N1pdm09 prospectively studied in 2009 and 142 patients with SARS-CoV-2 studied in 2020. Results: Patients with SARS-CoV-2 pneumonia were older (56 and 39.7 years respectively, p < 0.01) and had significantly more comorbidities. Cough, fever and myalgias were more frequent in influenza. Dyspnea was more frequent in COVID-19. Patients with COVID-19 had more extensive lung involvement and a longer hospitalization (13.6 and 8.6 days respectively, p = 0.01). There was no difference on ICU admission requirements and mortality attributable to pneumonia. Patients with influenza had greater APACHE scores and a higher frequency of a PaO2/FiO2 ratio ≤ 200. During COVID-19pandemic chest sean replaced x-ray examination. Also high-flow nasal cannulas and awake prone position ventilation were added as treatments. Conclusions: COVID-19 patients were older, had fewer classic flu symptoms but more dyspnea and longer hospitalization periods than patients with influenza.

Transglutaminase 2 inhibits the proliferation of H1 subtype influenza virus in MDCK cells / 生物工程学报

Transglutaminase 2 (TGM2) is a ubiquitous multifunctional protein, which is related to the adhesion of different cells and tumor formation. Previous studies found that TGM2 is involved in the interaction between host cells and viruses, but the effect of TGM2 on the proliferation of influenza virus in cells has not been reported. To explore the effect of TGM2 during H1N1 subtype influenza virus infection, a stable MDCK cell line with TGM2 overexpression and a knockout cell line were constructed. The mRNA and protein expression levels of NP and NS1 as well as the virus titer were measured at 48 hours after pot-infection with H1N1 subtype influenza virus. The results showed that overexpression of TGM2 effectively inhibited the expression of NP and NS1 genes of H1N1 subtype influenza virus, while knockout of TGM2 up-regulated the expression of the NP and NS1 genes, and the expression of the NP at protein level was consistent with that at mRNA level. Virus proliferation curve showed that the titer of H1N1 subtype influenza virus decreased significantly upon TGM2 overexpression. On the contrary, the virus titer in TGM2 knockout cells reached the peak at 48 h, which further proved that TGM2 was involved in the inhibition of H1N1 subtype influenza virus proliferation in MDCK cells. By analyzing the expression of genes downstream of influenza virus response signaling pathway, we found that TGM2 may inhibit the proliferation of H1N1 subtype influenza virus by promoting the activation of JAK-STAT molecular pathway and inhibiting RIG-1 signaling pathway. The above findings are of great significance for revealing the mechanism underlying the interactions between host cells and virus and establishing a genetically engineering cell line for high-yield influenza vaccine production of influenza virus.

Oxigenação por membrana extracorpórea na insuficiência respiratória em crianças: os anos antes e depois da pandemia de H1N1 de 2009 / Extracorporeal membrane oxygenation for respiratory failure in children: the years before and after the 2009 H1N1 pandemic

RESUMO Objetivo: Avaliar o impacto no número de casos de oxigenação por membrana extracorpórea e as taxas de sobrevivência nos anos seguintes à pandemia de H1N1 de 2009. Métodos: Avaliaram-se dois períodos distintos de utilização de oxigenação por membrana extracorpórea como suporte para insuficiência respiratória em crianças, por meio da análise de conjuntos de dados da Extracorporeal Life Support Organization. Foram construídos modelos autorregressivos integrados de médias móveis para estimar os efeitos da pandemia. O ano de 2009 foi o ano de intervenção (epidemia de H1N1) em um modelo de séries temporais interrompidas. Os dados colhidos entre 2001 e 2010 foram considerados pré-intervenção e os obtidos entre 2010 e 2017 como pós-intervenção. Resultados: Em comparação com o período entre 2001 e 2010, o período entre 2010 e 2017 mostrou aumento das taxas de sobrevivência (p < 0,0001), com melhora significante da sobrevivência quando se realizou oxigenação por membrana extracorpórea nos casos de insuficiência aguda por pneumonia viral. Antes do ponto de nível de efeito (2009), o modelo autorregressivo integrado de médias móveis mostrou aumento de 23 casos de oxigenação por membrana extracorpórea ao ano. Em termos de sobrevivência, a curva mostra que não houve aumento significante das taxas de sobrevivência antes de 2009 (p = 0,41), porém o nível de efeito foi próximo à significância após 2 anos (p = 0,05), com aumento de 6% na sobrevivência. Em 4 anos, ocorreu aumento de 8% (p = 0,03) na sobrevivência, e, 6 anos após 2009, a sobrevivência mostrou aumento de até 10% (p = 0,026). Conclusão: Nos anos após 2009, ocorreu significante e progressivo aumento global das taxas de sobrevivência com oxigenação por membrana extracorpórea para todos os casos, principalmente em razão de melhoras tecnológicas e dos protocolos de tratamento para insuficiência respiratória aguda relacionada à pneumonia viral e a outras condições respiratórias.

ABSTRACT Objective: To evaluate whether there was any impact on the number of pediatric extracorporeal membrane oxygenation runs and survival rates in the years subsequent to the 2009 pandemic. Methods: We studied two different periods of extracorporeal membrane oxygenation support for respiratory failure in children by analyzing datasets from the Extracorporeal Life Support Organization. Autoregressive integrated moving average models were constructed to estimate the effect of the pandemic. The year 2009 was the year of intervention (the H1N1 epidemic) in an interrupted time series model. Data collected from 2001 - 2010 were considered preintervention, and data collected from 2010 - 2017 were considered postintervention. Results: There was an increase in survival rates in the period 2010 - 2017 compared to 2001 - 2010 (p < 0.0001), with a significant improvement in survival when extracorporeal membrane oxygenation was performed for acute respiratory failure due to viral pneumonia. The autoregressive integrated moving average model shows an increase of 23 extracorporeal membrane oxygenation runs per year, prior to the point of the level effect (2009). In terms of survival, the preslope shows that there was no significant increase in survival rates before 2009 (p = 0.41), but the level effect was nearly significant after two years (p = 0.05), with a 6% increase in survival. In four years, there was an 8% (p = 0.03) increase in survival, and six years after 2009, there was up to a 10% (p = 0.026) increase in survival. Conclusion: In the years following 2009, there was a significant, global incremental increase in the extracorporeal membrane oxygenation survival rates for all runs, mainly due to improvements in the technology and treatment protocols for acute respiratory failure related to viral pneumonia and other respiratory conditions.

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.

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.

Development of a HA1-specific enzyme-linked immunosorbent assay against pandemic influenza virus A H1N1

PURPOSE: Enzyme-linked immunosorbent assay (ELISA) has been used in the diverse field to evaluate influenza virus infection; for the surveillance, diagnosis, efficacy evaluation, and development of the vaccine. The aim of this study was to establish an ELISA for detecting HA strain-specific antibodies using recombinant pandemic A H1N1 (pH1N1) HA1 (rHA1) protein. MATERIALS AND METHODS: rHA1 was produced in baculovirus system. The clinical performance of the developed ELISA was validated using human serum samples, by comparison with standard methods for detecting a neutralizing antibody; hemagglutination inhibition (HI) assay and microneutralization test (MNT). The ability of the ELISA system to evaluate the efficacy test of an influenza vaccine was explored by measuring antibody levels in the serum of vaccinated mice. RESULTS: Our ELISA could detect anti-rHA1 antibody in influenza-infected patients and vaccinated subjects. Compared to HI assay and MNT as reference methods, our method showed good performance in detection of anti-rHA1 antibody. Detection of the anti-rHA1 antibody in vaccinated mice and its correlation with titers in HI assay was also proved in a mice model. CONCLUSION: An ELISA system using rHA1 of pH1N1 influenza virus was developed, and showed good clinical performance in diagnosis of influenza virus infection and evaluation of the vaccination efficacy in both human and animal models.

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.

The expression of PDCD5 in peripheral blood of influenza A (H1N1) patients and the correlation with the severity of disease / 医学研究生学报

Objective The influenza A (H1N1) virus has the characteristic of strong infectiousness and variation. It can threaten the lives of patients. In this paper,we investigated the expression of programmed cell death molecule 5 (PDCD5) in peripheral blood of patients with influenza A (H1N1) and its correlation with the severity of disease. Methods The data of 104 patients with influenza A (H1N1) treated in Affiliated Hospital of Hebei University from January 2015 to December 2017 were analyzed retrospectively. The 104 patients were divided into the mild H1N1 group (n=78) and the severe H1N1 group (n=26). At the same time,104 healthy physical examination subjects were selected as control group. The blood routine,lymphocyte count and PDCD level were observed in three groups. Results The number of leukocytes,neutrophils and lymphocytes of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The number of leukocytes,neutrophils and lymphocytes of the severe H1N1 group were significantly lower than those of the mild H1N1 group (P<0.05). There was no significant difference in mononuclear cells between three groups (P>0.05). The levels of PDCD5 and lymphocyte apoptosis rate of the mild H1N1 group and severe H1N1 group were significantly higher than those of the control group (P<0.05) ,the severe H1N1 group was significantly higher than the mild H1N1 group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the mild H1N1 group and severe H1N1 group were significantly lower than those of the control group (P<0.05). The total T cells,CD4+T cells and CD8+T cells of the severe H1N1 group were significantly lower than those of the mild H1N1 group and con-trol group (P<0.05). The level of PDCD5 was positively correlated with the severity of disease and the rate of lymphocyte apoptosis (r=0.872,0.904,P<0.05),and negatively correlated with total T cells,CD4+T cells and CD8+T cells (r=-0.842,-0.805,-0.877,P<0.05). The sensitivity,specificity and area under the curve of PDCD5 to prediction of severe type H1N1 were 92.31%,97.25% and 0.941,respectively. Conclusion The level of peripheral blood PDCD5 in patients with influenza A (H1N1) virus in-fection is associated with the severity of the disease,and it can be considered as an important biomarker to predict severe influenza A (H1N1).

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.

Encefalitis hemorrágica por influenza A H1N1: presentación de un caso y revisión de la literatura / H1N1 influenza hemorrhage encephalitis: presentation of a case and review of the literature

RESUMEN Las complicaciones neurológicas asociadas a los virus respiratorios (en especial la influenza) son descritas de manera poco frecuente. Particularmente el virus influenza A subtipo H1N1 tiene escasos reportes, la mayoría proviene de niños y adultos jóvenes. Presentamos el caso del adulto mayor con un cuadro infeccioso respiratorio y múltiples complicaciones sistémicas graves a su cuadro primario, quien durante la estancia hospitalaria presentó un cuadro encefalopático, con características clínicas y radiológicas muy sugestivas de encefalitis hemorrágica debido a su agente primario infeccioso, en este caso influenza A H1N1.

SUMMARY Neurological complications associated with respiratory viruses such as influenza, are described infrequently. Particularly influenza A(H1N1) has few descriptions most of which come from children and young adults. We present the case of the elderly with respiratory infectious picture and multiple serious systemic complications to your primary table, who during the hospital stay has a encephalopathic box with suggestive clinical and radiologic features of hemorrhagic encephalitis due to its infectious primary agent in this case influenza A H1N1.

Deshidrogenasa láctica como factor pronóstico en neumonías / Lactic dehydrogenase as a prognostic factor in pneumonias

Resumen ANTECEDENTES: la pandemia de influenza en 2009 renovó el interés por identificar oportunamente casos sospechosos de influenza mediante estudios de laboratorio rutinarios, uno de los más estudiados es la deshidrogenasa láctica (DHL). OBJETIVO: determinar si los pacientes con neumonía por influenza A (H1N1) tienen alteraciones particulares en estudios rutinarios de laboratorio, particularmente en concentraciones de DHL y analizar la implicación pronóstica. MATERIAL Y MÉTODO: estudio de casos y controles de pacientes con diagnóstico confirmado de neumonía por influenza A (H1N1) [caso], y pacientes con neumonía bacteriana (control) atendidos de diciembre de 2013 a julio de 2014. RESULTADOS: se analizaron 31 casos, 45% (n = 14) tenían diagnóstico de neumonía por el virus de la influenza A (H1N1), el 55% restante (n = 17) se consideró de causa bacteriana. La media de edad fue de 38 años (límites: 16-62). Las concentraciones de DHL al momento del diagnóstico fueron, en promedio, de 578.77 UI/L (límites: 191-1096), fue mayor en el grupo con neumonía por influenza A (H1N1) [573 vs 624.7 UI/L, p = 0.366]. En el análisis global las concentraciones de DHL > 350 UI/L al diagnóstico y fin del tratamiento repercutieron fuertemente de manera negativa en la mortalidad (OR: 84.0, IC95%: 4.4754-1576.6044 y OR: 154.0, 8.6261-2749.3255). La supervivencia general fue de 18 días, menor en el grupo de A (H1N1) [4 vs 25 días, p = 0.016). CONCLUSIONES: las concentraciones de DHL > 350 UI/L pueden considerarse un biomarcador de gravedad y repercuten negativamente en la supervivencia de pacientes con neumonía, sin poder discriminar al posible agente etiológico.

Abstract BACKGROUND: The 2009 influenza pandemic renewed interest in timely identification of suspected influenza cases through routine laboratory studies, the most studied is lactic dehydrogenase (DHL). OBJECTIVE: To determine if patients with influenza A (H1N1) pneumonia present particular alterations inside routine laboratory studies, particularly in DHL levels and analyze the prognostic implication. MATERIAL AND METHOD: A case-control study of patients with confirmed diagnosis of influenza A (H1N1) pneumonia (case), and patients with bacterial pneumonia (control) treated from December 2013 to July 2014. RESULTS: Thirty-one cases were analyzed, 45% (n = 14) had a diagnosis of influenza A (H1N1) pneumonia, the remaining 55% (n = 17) was considered of bacterial etiology. The mean age was 38 (16-62) years old. The DHL level at diagnosis time was on average 578.77 IU/L (191-1096), higher in the group with influenza A (H1N1) pneumonia (573 IU/L vs 624.7 IU/L, p = 0.366). In the overall analysis, the levels of DHL > 350 IU/L at diagnosis time and at the end of treatment had a negative impact on mortality (OR: 84.0, 95%CI: 4.4754-1576.6044, and OR: 154.0, 8.6261-2749.3255). Overall survival was 18 days, lower in the A (H1N1) group (4 vs 25 days, p = 0.016). CONCLUSIONS: DHL > 350 IU/L can be considered a severity biomarker, also has a negative impact on the survival of patients with pneumonia without being able to discriminate the possible etiological agent.

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.