Uso del péptido CIGB-258 en un paciente pediátrico con neumonía grave por SARS-CoV-2 / Use of CIGB-258 peptide in a pediatric patient with severe pneumonia due to SARS-CoV-2

Introducción: La presentación clínica de la enfermedad provocada por el SARS-CoV-2 es heterogénea. Los pacientes pueden ser asintomáticos o tener una enfermedad leve de las vías respiratorias superiores o desarrollar una neumonía grave que puede progresar al síndrome de dificultad respiratoria aguda y provocar la muerte. La fisiopatología de las formas graves de la enfermedad se caracteriza por una marcada hiperinflamación. Las terapias que modulan la respuesta inmunitaria pueden ser cruciales para tratar y prevenir este estado. El péptido CIGB-258, marca comercial Jusvinza, es una opción terapéutica para este propósito, por sus propiedades inmunomoduladoras. Objetivo: Describir la evolución clínica de un paciente pediátrico con neumonía grave por SARS-CoV-2, tratado con el péptido CIGB-258 Presentación del caso: Adolescente de 12 años con epilepsia refractaria, parálisis cerebral infantil y antecedentes epidemiológicos de contacto con paciente positivo a test confirmatorio de reacción en cadena de la polimerasa con transcriptasa inversa para SARS-CoV-2 que ocho días después del contacto, muestra evidencias clínicas, radiográficas y de laboratorio de neumonía grave por COVID-19. Dentro del protocolo terapéutico, recibió tratamiento con el péptido inmunomodulador CIGB-258, con una evolución favorable y egreso hospitalario. Conclusiones: El uso del péptido CIGB-258 en el tratamiento de la neumonía grave por COVID-19 en pediatría, podría contribuir a evitar la progresión hacia las etapas críticas de la enfermedad(AU)

Introduction: The clinical presentation of the disease caused by SARS-CoV-2 is heterogeneous. Patients may be asymptomatic or have mild upper respiratory tract disease, or develop severe pneumonia that can progress to acute respiratory distress syndrome and lead to death. The pathophysiology of severe forms of the disease is characterized by a marked hyperinflammation. Therapies that modulate the immune response can be crucial in treating and preventing this state. The CIGB-258 peptide, brand name Jusvinza, is a therapeutic option for this purpose, due to its immunomodulatory properties. Objective: Describe the clinical evolution of a pediatric patient with severe pneumonia due to SARS-CoV-2, and treated with the CIGB-258 peptide. Case Presentation: A 12-year-old adolescent with refractory epilepsy, infantile cerebral palsy, and an epidemiological history of contact with a patient positive to PCR confirmatory test for SARS-CoV-2 who, eight days after contact, shows clinical, radiographic, and laboratory evidence of severe pneumonia due to COVID-19. Within the therapeutic protocol, he received treatment with CIGB-258 immunomodulatory peptide, with a favorable evolution and hospital discharge. Conclusions: The use of CIGB-258 peptide in the treatment of severe pneumonia due to COVID-19 in pediatrics could contribute to prevent progression to the critical stages of the disease(AU)

Cuadro clínico del COVID-19 / Clinical presentation of COVID-19

El Coronavirus SARS-CoV-2 produce la enfermedad COVID-19, cuya manifestación más grave y potencialmente letal es la neumonía. En este artículo revisaremos las manifestaciones clínicas del COVID-19, la fisiopatología de la neumonía, el manejo intrahospitalario previo al ingreso a Unidades de Cuidados Intensivos, la embolia pulmonar que es una complicación muy frecuente de esta enfermedad y el seguimiento de los pacientes posterior al alta. Para esta publicación nos hemos basado en publicaciones médicas y en estudios que hemos hecho durante esta pandemia en nuestro Centro de Enfermedades Respiratorias. i:es

The SARS-CoV-2 Coronavirus causes the COVID-19 disease, the most severe and potentially fatal manifestation of which is pneumonia. In this article, we will review the clinical manifestations of COVID-19, the pathophysiology of pneumonia, in-hospital management prior to admission to Intensive Care Units, pulmonary embolism, which is a very frequent complication of this disease, and the follow-up of patients after hospitalization. For this publication we have relied on medical publications and studies that we have done during this pandemic at our Center for Respiratory Diseases. i:en

Effect of coinfection with influenza virus and bacteria on host damage / Efecto de la coinfección por virus de la influenza y bacterias en el daño al hospedero

Abstract Background: Influenza virus infection is often complicated by a bacterial infection, with this coinfection causing severe pneumonia. If not timely treated, the disease can cause death. Objective: To demonstrate, in animal models, that coinfection with influenza virus and bacteria that affect the respiratory tract causes multisystemic damage. Method: Six groups of mice were formed: a control group, one infected with the influenza virus, two infected with bacteria: Haemophilus influenzae and Streptococcus pneumoniae, respectively; and two co-infected with influenza virus and Haemophilus influenzae or Streptococcus pneumoniae, respectively. Results: Of the six groups of mice, only the group co-infected with influenza virus and Streptococcus pneumoniae showed damage to thoracic and abdominal organs. A decrease in serum cytokine levels was found in all study groups, which was more pronounced in the co-infected mice. Conclusions: The groups of mice infected with Streptococcus pneumoniae or influenza virus alone showed no damage, which indicates that coexistence of these infections caused the damage in the group of co-infected mice.

Resumen Antecedentes: La infección por el virus de la influenza con frecuencia se complica con una infección bacteriana, coinfección que provoca cuadros graves de neumonía, la cual puede ocasionar la muerte si no es tratada en forma oportuna. Objetivo: Demostrar en modelos animales que la coinfección por el virus de la influenza y bacterias que afectan el tracto respiratorio ocasiona daño multisistémico. Método: Se formaron seis grupos de ratones: un grupo control, uno infectado de virus de la influenza, dos infectados de bacterias: Haemophilus influenzae y Streptococcus pneumoniae, respectivamente; y dos coinfectados de virus de la influenza y Haemophilus influenzae y Streptococcus pneumoniae, respectivamente. Resultados: De los seis grupos de ratones, solo en el grupo coinfectado de virus de la influenza y Streptococcus pneumoniae se observó daño en órganos torácicos y abdominales. En todos los grupos se encontró disminución de los niveles séricos de las citocinas, mayor en los ratones coinfectados. Conclusiones: Los grupos de ratones infectados solo de Streptococcus pneumoniae o el virus de la influenza no presentaron daños, lo cual indica que la coexistencia de estas infecciones fue la que ocasionó el daño en el grupo de ratones coinfectados.

Infection in Patients with Decompensated Heart Failure: In-Hospital Mortality and Outcome / Infecção em Pacientes com Insuficiência Cardíaca Descompensada: Mortalidade Hospitalar e Evolução

Abstract Background: Heart failure (HF) is a syndrome, whose advanced forms have a poor prognosis, which is aggravated by the presence of comorbidities. Objective: We assessed the impact of infection in patients with decompensated HF admitted to a tertiary university-affiliated hospital in the city of São Paulo. Methods: This study assessed 260 patients consecutively admitted to our unit because of decompensated HF. The presence of infection and other morbidities was assessed, as were in-hospital mortality and outcome after discharge. The chance of death was estimated by univariate logistic regression analysis of the variables studied. The significance level adopted was P < 0.05. Results: Of the patients studied, 54.2% were of the male sex, and the mean age ± SD was 66.1 ± 12.7 years. During hospitalization, 119 patients (45.8%) had infection: 88 (33.8%) being diagnosed with pulmonary infection and 39 patients (15.0%), with urinary infection. During hospitalization, 56 patients (21.5%) died, and, after discharge, 36 patients (17.6%). During hospitalization, 26.9% of the patients with infection died vs 17% of those without infection (p = 0.05). However, after discharge, mortality was lower in the group that had infection: 11.5% vs 22.2% (p = 0.046). Conclusions: Infection is a frequent morbidity among patients with HF admitted for compensation of the condition, and those with infection show higher in-hospital mortality. However, those patients who initially had infection and survived had a better outcome after discharge.

Resumo Fundamento: A insuficiência cardíaca (IC) é uma síndrome cujas formas avançadas têm mau prognóstico, que é mais agravado pela presença de comorbidades. Objetivo: Avaliamos o impacto da infecção em pacientes com IC descompensada que internaram em hospital universitário terciário de São Paulo. Métodos: Estudamos 260 pacientes consecutivos que internaram em nossa unidade com IC descompensada. Avaliamos a presença de infecção e de outras morbidades. Avaliaram-se mortalidade hospitalar e evolução após a alta. A chance de óbito foi estimada pela análise de regressão logística univariada para as variáveis estudadas. Considerou-se P < 0,05 significativo. Resultados: Dos pacientes estudados, 54,2% eram homens, sendo a idade média ± DP de 66,1 ± 12,7 anos. Durante a internação, 119 pacientes (45,8%) apresentaram infecção: 88 (33,8%) tiveram diagnóstico de infecção pulmonar e 39 (15%), de infecção urinária. A mortalidade hospitalar ocorreu em 56 pacientes (21,5%) e, após a alta, 36 pacientes (17,6%) morreram no seguimento. Durante a internação, 26,9% do grupo com infecção morreu vs 17% do grupo sem infecção (p = 0,05). Entretanto, após a alta, a mortalidade foi menor no grupo com infecção: 11,5% vs 22,2% (p = 0,046). Conclusões: Infecção é uma comorbidade frequente entre os pacientes com IC internados para compensação, causando um aumento da mortalidade durante a hospitalização. Entretanto, após a alta, os pacientes inicialmente com infecção apresentaram melhor evolução.

Short-term effects of stored homologous red blood cell transfusion on cardiorespiratory function and inflammation: an experimental study in a hypovolemia model

The pathophysiological mechanisms associated with the effects of red blood cell (RBC) transfusion on cardiopulmonary function and inflammation are unclear. We developed an experimental model of homologous 14-days stored RBC transfusion in hypovolemic swine to evaluate the short-term effects of transfusion on cardiopulmonary system and inflammation. Sixteen healthy male anesthetized swine (68±3.3 kg) were submitted to controlled hemorrhage (25% of blood volume). Two units of non-filtered RBC from each animal were stored under blood bank conditions for 14 days. After 30 min of hypovolemia, the control group (n=8) received an infusion of lactated Ringer's solution (three times the removed volume). The transfusion group (n=8) received two units of homologous 14-days stored RBC and lactated Ringer's solution in a volume that was three times the difference between blood removed and blood transfusion infused. Both groups were followed up for 6 h after resuscitation with collection of hemodynamic and respiratory data. Cytokines and RNA expression were measured in plasma and lung tissue. Stored RBC transfusion significantly increased mixed oxygen venous saturation and arterial oxygen content. Transfusion was not associated with alterations on pulmonary function. Pulmonary concentrations of cytokines were not different between groups. Gene expression for lung cytokines demonstrated a 2-fold increase in mRNA level for inducible nitric oxide synthase and a 0.5-fold decrease in mRNA content for IL-21 in the transfused group. Thus, stored homologous RBC transfusion in a hypovolemia model improved cardiovascular parameters but did not induce significant effects on microcirculation, pulmonary inflammation and respiratory function up to 6 h after transfusion.

Valor prognóstico da procalcitonina em pacientes com infecções do trato respiratório inferior no ambiente hospitalar / Prognostic value of procalcitonin in hospitalized patients with lower respiratory tract infections

RESUMO Infecções do trato respiratório inferior são condições frequentes e potencialmente letais, consistindo nas principais causas de prescrição inadequada de antibióticos. A caracterização de sua gravidade e a predição prognóstica dos pacientes acometidos auxiliam na condução, permitindo maior acerto nas decisões sobre a necessidade e o local de internação, assim como a duração do tratamento. A incorporação de biomarcadores às estratégias classicamente utilizadas representa estratégia promissora, com destaque para a procalcitonina. O objetivo deste artigo foi apresentar uma revisão narrativa sobre a potencial utilidade e as limitações do uso da procalcitonina como um marcador prognóstico em pacientes hospitalizados portadores de infecções do trato respiratório inferior. Os estudos publicados sobre o tema são heterogêneos, no que tange à variedade de técnicas de mensuração da procalcitonina, seus valores de corte, os contextos clínicos e a gravidade dos pacientes incluídos. Os dados obtidos indicam valor moderado da procalcitonina para predizer o prognóstico de pacientes com infecções do trato respiratório inferior, não superior a metodologias classicamente utilizadas, e com utilidade que se faz notar apenas quando interpretados junto a outros dados clínicos e laboratoriais. De modo geral, o comportamento da procalcitonina, ao longo dos primeiros dias de tratamento, fornece mais informações prognósticas do que sua mensuração em um momento isolado, mas faltam informações sobre a custo-efetividade dessa medida em pacientes em terapia intensiva. Estudos que avaliaram o papel prognóstico da procalcitonina inicial em pacientes com pneumonia adquirida na comunidade apresentam resultados mais consistentes e com maior potencial de aplicabilidade prática, mas com utilidade limitada a valores negativos para a seleção de pacientes com baixo risco de evolução desfavorável.

ABSTRACT Lower respiratory tract infections are common and potentially lethal conditions and are a major cause of inadequate antibiotic prescriptions. Characterization of disease severity and prognostic prediction in affected patients can aid disease management and can increase accuracy in determining the need for and place of hospitalization. The inclusion of biomarkers, particularly procalcitonin, in the decision taken process is a promising strategy. This study aims to present a narrative review of the potential applications and limitations of procalcitonin as a prognostic marker in hospitalized patients with lower respiratory tract infections. The studies on this topic are heterogeneous with respect to procalcitonin measurement techniques, cutoff values, clinical settings, and disease severity. The results show that procalcitonin delivers moderate performance for prognostic prediction in patients with lower respiratory tract infections; its predictive performance was not higher than that of classical methods, and knowledge of procalcitonin levels is most useful when interpreted together with other clinical and laboratory results. Overall, repeated measurement of the procalcitonin levels during the first days of treatment provides more prognostic information than a single measurement; however, information on the cost-effectiveness of this procedure in intensive care patients is lacking. The results of studies that evaluated the prognostic value of initial procalcitonin levels in patients with community-acquired pneumonia are more consistent and have greater potential for practical application; in this case, low procalcitonin levels identify those patients with a low risk of adverse outcomes.

Tratamento da pneumonia grave adquirida na comunidade no Brasil: análise secundária de um inquérito internacional / Management of severe community-acquired pneumonia in Brazil: a secondary analysis of an international survey

Objetivo: Avaliar a percepção dos médicos brasileiros quanto ao diagnóstico, à avaliação de gravidade, ao tratamento e à estratificação de risco em pacientes com pneumonia grave adquirida na comunidade, e compará-la com as diretrizes atuais. Métodos: Estudo transversal realizado por meio da aplicação de um questionário anônimo a uma amostra de médicos brasileiros especialistas em cuidados intensivos, medicina de emergência, medicina interna e pneumologia. Entre outubro e dezembro de 2008, foram avaliadas as atitudes dos médicos no diagnóstico, a avaliação de risco e as intervenções terapêuticas para pacientes com pneumonia grave adquirida na comunidade. Resultados: Responderam ao questionário 253 médicos, sendo 66% da Região Sudeste do Brasil. A maioria (60%) dos médicos que responderam tinha mais de 10 anos de experiência. Verificou-se que a avaliação de risco de pneumonia grave adquirida na comunidade foi muito heterogênea, sendo a avaliação clínica a forma de avaliação de risco mais frequente. As hemoculturas foram habitualmente realizadas por 75% dos médicos, entretanto, foi reconhecido seu fraco desempenho diagnóstico. Por outro lado, a pesquisa de antígenos urinários de Pneumococo e Legionella foi solicitada por menos de um terço dos médicos. A maioria (95%) prescreveu antibióticos de acordo com as diretrizes. A combinação de uma cefalosporina de terceira ou quarta geração com um macrolídeo foi a escolha mais comum. Conclusão: Este inquérito brasileiro demonstrou diferenças entre as diretrizes publicadas e a prática clínica. Isso leva à necessidade de se desenvolverem programas educacionais e de adoção de protocolos para implementar estratégias baseadas em evidências no manejo da pneumonia grave adquirida na comunidade. .

Objective: This study aimed to evaluate Brazilian physicians’ perceptions regarding the diagnosis, severity assessment, treatment and risk stratification of severe community-acquired pneumonia patients and to compare those perceptions to current guidelines. Methods: We conducted a cross-sectional international anonymous survey among a convenience sample of critical care, pulmonary, emergency and internal medicine physicians from Brazil between October and December 2008. The electronic survey evaluated physicians’ attitudes towards the diagnosis, risk assessment and therapeutic interventions for patients with severe community-acquired pneumonia. Results: A total of 253 physicians responded to the survey, with 66% from Southeast Brazil. The majority (60%) of the responding physicians had > 10 years of medical experience. The risk assessment of severe community-acquired pneumonia was very heterogeneous, with clinical evaluation as the most frequent approach. Although blood cultures were recognized as exhibiting a poor diagnostic performance, these cultures were performed by 75% of respondents. In contrast, the presence of urinary pneumococcal and Legionella antigens was evaluated by less than 1/3 of physicians. The vast majority of physicians (95%) prescribe antibiotics according to a guideline, with the combination of a 3rd/4th generation cephalosporin plus a macrolide as the most frequent choice. Conclusion: This Brazilian survey identified an important gap between guidelines and clinical practice and recommends the institution of educational programs that implement evidence-based strategies for the management of severe community-acquired pneumonia. .

Estudo do envolvimento do receptor nuclear PPAR gama no controle de infecções / The involvement of the nuclear receptor ppar gamma in infection control

A pneumonia é uma infecção aguda localizada nos pulmões geralmenteassociada à bactéria Gram-negativa, sendo a Pseudomonas aeruginosa um dosprincipais agentes etiológicos. O processo infeccioso no trato respiratório estß associadoà sepse, caracterizada como síndrome de resposta inflamatória (SIRS) originada poruma infecção. Hß um grande número de pacientes em ventilação mecânica nas unidadesde terapia intensiva com sepse. Durante a invasão de um microorganismo o sistemaimune é ativado dando inicio a uma resposta inflamatória. Os neutrófilos são asprimeiras células a chegarem ao local da infecção. Recentemente, foi descrito um tipode morte celular dos neutrófilos denominado NETose, que leva à formação de redesextracelulares dos neutrófilos (NET). Na NETose componentes do DNA e proteínas sãolançados para o meio extracelular formando as redes, levando à captura e eliminação dopatógeno invasor. Alguns estudos do nosso laboratório e de outros autores mostraram arelação do receptor nuclear ativado por proliferadores de peroxissomos gama (PPARγ)com o processo inflamatório, capaz de inibir a expressão de genes de mediadores pró-inflamatórios. A rosiglitazona, uma droga agonista do PPARγ, modulou a respostainflamatória na sepse polimicrobiana de origem peritoneal em camundongos. O presentetrabalho analisou o efeito deste fßrmaco na infecção bacteriana causada pelaPseudomonas aeruginosa e no modelo de sepse polimicrobiana. Investigamos os efeitosda instilação de Pseudomonas aeruginosa e do tratamento com rosiglitazona sobre ossinais clínicos dos camundongos Swiss, o número de leucócitos totais e diferenciais,produção de citocinas, na formação de NET e no crescimento bacteriano...

The pneumonia is an acute infection localized in the lungs usually associated to a Gramnegativebacterium. Pseudomonas aeruginosa is one of the principal etiological agents.The respiratory tract infection process is associated with sepsis, characterized assystemic inflammatory response syndrome (SIRS) caused by an infection. There is ahigh number of patients under mechanical ventilation in intensive care units affectedwith sepsis. During a microorganism invasion the immune system is activated startingan inflammatory response. The neutrophils are the first cells to migrate to the infectionsite. Recently it was described a new type of neutrophil cellular death called NETosis,which leads to the neutrophil extracellular trap formation (NET). There is release ofcomponents of DNA and proteins to the extracellular medium forming traps inNETosis, leading to the capture and elimination of the pathogens. We and other authorsobserved the relation between the peroxisome proliferator-activated receptor gamma(PPARγ) and the inflammatory process. Beyond its role in the lipid metabolism and theglycemia regulation, PPARγ inhibits the inflammatory mediator gene expression. Therosiglitazone, a PPARγ agonist, modulated the inflammatory response in polymicrobialsepsis in mice. The present work aimed to analyze the effect of this drug in the infectioncaused by Pseudomonas aeruginosa and in the polymicrobial sepsis model. Weinvestigated the effects of Pseudomonas aeruginosa instillationin mice and thetreatment with rosiglitazone on the clinical signs, the number of total and differentialleukocytes, cytokine production, NET formation and bacterial growth. Rosiglitazonetreatment stabilized the respiratory rate showing a protective effect in the focus ofinfection, as well as a reduction of onset the disease clinical signs. We also observed adecrease in pro-inflammatory cytokine production and the increased elimination ofbacteria in rosiglitazone-treated septic animals...

Postperfusion lung syndrome: physiopathology and therapeutic options / Síndrome pós-perfusão pulmonar: fisiopatologia e opções terapêuticas

Postperfusion lung syndrome is rare but can be lethal. The underlying mechanism remains uncertain but triggering inflammatory cascades have become an accepted etiology. A better understanding of the pathophysiology and the roles of inflammatory mediators in the development of the syndrome is imperative in the determination of therapeutic options and promotion of patients' prognosis and survival. Postperfusion lung syndrome is similar to adult respiratory distress syndrome in clinical features, diagnostic approaches and management strategies. However, the etiologies and predisposing risk factors may differ between each other. The prognosis of the postperfusion lung syndrome can be poorer in comparison to acute respiratory distress syndrome due to the secondary multiple organ failure and triple acid-base imbalance. Current management strategies are focusing on attenuating inflammatory responses and preventing from pulmonary ischemia-reperfusion injury. Choices of cardiopulmonary bypass circuit and apparatus, innovative cardiopulmonary bypass techniques, modified surgical maneuvers and several pharmaceutical agents can be potential preventive strategies for acute lung injury during cardiopulmonary bypass.

Síndrome pós-perfusão pulmonar é rara, mas pode ser letal. O mecanismo subjacente permanece incerto, mas desencadear cascatas inflamatórias tornou-se uma etiologia aceita. É imperativo uma melhor compreensão da fisiopatologia e os papéis de mediadores inflamatórios no desenvolvimento da síndrome na determinação de opções terapêuticas e de promoção do prognóstico e sobrevida dos pacientes. Síndrome pós-perfusão pulmonar é semelhante à síndrome da angústia respiratória do adulto em características clínicas, métodos diagnósticos e estratégias de gestão. No entanto, as etiologias e fatores de risco predisponentes podem ser diferentes entre si. O prognóstico da síndrome pós-perfusão pulmonar pode ser mais pobres em comparação com síndrome da angústia respiratória aguda, devido à falência de múltiplos órgãos secundária e desequilíbrio ácido-base triplo. Estratégias de gestão atuais centram-se em atenuar reações inflamatórias e impedir lesão pulmonar de isquemia-reperfusão. Escolhas do circuito de circulação extracorpórea e aparelhos, técnicas inovadoras de circulação extracorpórea, manobras cirúrgicas modificadas e vários agentes farmacêuticos podem ser potenciais estratégias preventivas para lesão pulmonar aguda durante a circulação extracorpórea.

Effects of atropine and propranolol on lung inflammation in experimental envenomation: comparison of two buthidae venoms

Background: Previous works had shown that scorpion venom induced neurotransmitter elevation and an inflammatory response associated with various anatomo-pathological modifications. The most dangerous scorpions species in Algeria responsible for these effects are Androctonus australis hector (Aah) and Androctonus amoreuxi (Aam). Results: Comparison of the physiopathological effects induced by the two venoms showed differences in the kinetic of cytokine release and in lung injury. The lung edema was only observed in response to Aah venom and it was correlated with cell infiltration. In order to better understand the involved mechanism in inflammatory response, we used two antagonists, atropine (non-selective muscarinic antagonist) and propranolol (ß adrenergic antagonist), which lead to a decrease of cell infiltration but has no effect on edema forming. Conclusion: These results suggest another pathway in the development of lung injury following envenomation with Aam or Aah venom.(AU)

Effects of Diet-Induced Mild Obesity on Airway Hyperreactivity and Lung Inflammation in Mice

PURPOSE: Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity-related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity. MATERIALS AND METHODS: We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) beta, and tumor necrosis factor (TNF) alpha in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid. RESULTS: Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge. CONCLUSION: Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.

Influence of asymptomatic pneumonia on the response to hemorrhage and resuscitation in swine

INTRODUCTION: Investigation of resuscitation fluids in our swine hemorrhage model revealed moderate to severe chronic pneumonia in five swine at necropsy. Our veterinary staff suggested that we perform a retrospective analysis of prospectively collected data from these animals. We compared the data to that of ten healthy swine to determine the physiologic consequences of the added stress on our hemorrhage/resuscitation model. METHODS: Anesthetized, immature female swine (40 ± 5 kg) were instrumented for determining arterial and venous pressures, cardiac output and urine production. A controlled hemorrhage of 20 ml/kg over 4 min 40 sec was followed at 30 min by a second hemorrhage of 8 ml/kg and resuscitation with 1.5 ml/kg/min of LR solutions to achieve and maintain systolic blood pressure at 80 ± 5 mmHg for 3.5 hrs. Chemistries and arterial and venous blood gasses were determined from periodic blood samples along with hemodynamic variables. RESULTS: There were significant decreases in survival, urine output, cardiac output and oxygen delivery at 60 min and O2 consumption at 120 min in the pneumonia group compared to the non-pneumonia group. There were no differences in other metabolic or hemodynamic data between the groups. CONCLUSION: Although pneumonia had little influence on pulmonary gas exchange, it influenced cardiac output, urine output and survival compared to healthy swine, suggesting a decrease in the physiologic reserve. These data may be relevant to patients with subclinical infection who are stressed by hemorrhage and may explain in part why some similarly injured patients require more resuscitation efforts than others.

A influência de sintomas de depressão na frequência de complicações pós-operatórias precoces de pacientes submetidos a cirurgia torácica / The influence of symptoms of depression on the early postoperative complications of thoracic surgical patients

Introdução: É sabido que a depressão exerce papel deletério no pós-operatório de cirurgias ortopédicas e cardiovasculares. Objetivo: Avaliar a influência de sintomas depressivos sobre a ocorrência de complicações no período pós-operatório precoce de pacientes submetidos a cirurgia torácica não cardíaca. Metodologia: Como desenho foi definido uma série de casos prospectiva. Cenário: hospital universitário terciário. Sujeitos: quarenta e oito pacientes (idade média: 62±9 anos; 29 homens) tratados com toracotomia e ressecção de parênquima pulmonar pneumonectomia (16,6 por cento); lobectomia ou ressecção menor (83,4 por cento). Métodos: candidatos consecutivos a cirurgia torácica não cardíaca a céu aberto tiveram seus níveis de depressão avaliados na semana anterior ao procedimento cirúrgico utilizando-se o Inventário Beck de Depressão (BDI). As equipes cirúrgica e clínica e o paciente eram cegos para o resultado de BDI. As seguintes variáveis foram coletadas e registradas após a realização do procedimento cirúrgico: 1) tempo de permanência em unidade de tratamento intensivo (UTI) superior a três dias; 2) necessidade de ventilação mecânica secundária a insuficiência respiratória; 3) pneumonia; e 4) necessidade de reintervenção cirúrgica. Resultados: houve diferença significativa de 10,2 pontos (IC95 por cento: 20,37 a 0,02) nos índices pré-operatórios de BDI entre pacientes que desenvolveram ou não desenvolveram pneumonia no pós-operatório, 21,0±9,5 e 10,8±8,2, respectivamente (p=0,04). Conclusões: estado depressivo pode afetar negativamente o pós-operatório precoce de pacientes submetidos a cirurgia torácica não cardíaca, levando a um aumento na taxa de pneumonias.

Introduction: It is known that depression plays a deleterious role in the postoperative recovery of patients submitted to orthopedic and cardiovascular surgeries. Aim: To evaluate the influence of depression symptoms on the occurrence of postoperative complications in patients submitted to non-cardiac thoracic surgeries. Methods: The design was a prospective case series. Setting: Tertiary school hospital. Subjects: 48 patients (mean age 62±9 years; 29 males) submitted to thoracotomy and resection of the pulmonary parenchyma pneumonectomy (16.6 percent); lobectomy or smaller resection (83,4 percent). Methods: Consecutive candidates to non-cardiac open thoracic surgery had their levels of depression evaluated one week before the surgical procedure using the Beck Depression Inventory (BDI). The clinical and surgical teams and the patient were blind to the BID result. The following variables were collected and recorded after the performance of the surgical procedure: 1) time of stay in the intensive care unit (ICU) above 3 days; 2) need for mechanical ventilation secondary to respiratory failure; 3) pneumonia; and 4) need for surgical reintervention. Results: There was a significant difference of 10.2 points (CI95 percent: 20.37 to 0.02) in the BDI preoperative indexes among the patients who developed or did not develop pneumonia in the post-operative period (21.0±9.5 and 10.8±8.2, respectively) (p=0.04). Conclusions: A depressive state may adversely affect the early postoperative recovery of patients submitted to non-cardiac thoracic surgeries, leading to an increase in the rate of pneumonias.

Indirect calorimetry can be used to measure cardiac output in septic patients? / A calorimetria indireta pode ser utilizada para medir o débito cardíaco em pacientes sépticos?

PURPOSE: The aim of this study was to compare two different cardiac output (CO) monitoring systems based on the thermodilution principle (Thermo-CO) and indirect calorimetry (Fick mixed-CO) in septic patients. METHODS: Prospective study in septic patients admitted in an intensive care unit of a university hospital. Nineteen patients aged on average 45.4 ± 21.5 years were enrolled in the study. Four series of hourly measurements by the two techniques were carried out simultaneously. RESULTS: No significant differences were observed between Thermo-CO and Fick mixed-CO (7.0 ± 1.8 L.min-1 and 6.4 ± 1.7 L.min-1.). Parallel analysis of Fick mixed-CO and Fick atrial-CO was performed introducing a correction factor for the eight atrial samples in order to adjust the values of oxygen saturation obtained from atrial blood (Fick corrected atrial-CO) to those obtained from mixed venous blood. No significant differences could be detected between Fick mixed-CO and Fick corrected atrial-CO. The correlation coefficients of Thermo CO/Fick mixed-CO and Fick mixed-CO/Fick corrected atrial-CO were 0.84 and 0.94, respectively. CONCLUSION: We observed that the agreement between the two methods was satisfactory on the basis of the decisions made for treatment. Indirect calorimetry is useful to measure CO in patients with septic shock.

OBJETIVO: O objetivo deste estudo foi comparar as medidas do débito cardíaco (DC) obtidas pela termodiluição (DC-termo) e pela calorimetria indireta (DC-Fick misto) em pacientes com choque séptico. MÉTODOS: Estudo prospectivo em pacientes sépticos internados em unidade de terapia intensiva de um hospital universitário. Foram estudados 19 pacientes (45,4 ± 21,5 anos). Foram realizadas quatro séries de medidas do DC pelos dois métodos, simultaneamente. RESULTADOS: Não houve diferenças significativas entre os valores do DC-termo e DC-Fick misto (7,0 ± 1,8 L.min-1 e 6,4 ± 1,7 L.min-1, respectivamente). Na avaliação dos oito casos (DC-Fick misto/DC Fick atrial), introduziu-se um fator de correção para aproximar os valores do conteúdo de O2 atrial (DC-Fick atrial corrigido) com o venoso misto. Não houve diferença significativa do DC-Fick misto e DC-Fick atrial corrigido nos 4 tempos. A correlação foi de 0.84 para o DC-termo/DC-Fick misto e de 0.94 para o DC-Fick misto/DC-Fick atrial corrigido. CONCLUSÃO: A calorimetria indireta é um bom método para a medida do DC em pacientes vítimas de choque séptico, sobretudo nos casos onde a monitorização hemodinâmica invasiva não está disponível ou está contra indicada.

Manifestaciones iniciales de la infección por el virus de inmunodeficiencia humana en pediatría: premio Doctor Juan Guido Tatá": LIII Congreso Nacional de Pediatría 2007 / Initial manifestations of human immunodeficiency in pediatrics: prize Doctor Juan Guido Tatá: LIII National Congress of Peditrics 2007

La infección VIH en pediatría, muestra diversidad de manifestaciones cuyo reconocimiento permite una precoz aproximación diagnóstica. Determinar las manifestaciones inicieales en pacientes pediátricos con infección VIH. Estudio comparativo y retrospectivo, incluyendo pacientes con infección VIH del Hospital de Niños "J.M de Los Ríos" (Caracas, Venezuela) entre 1987-2006. Los datos fueron obtenidos de la base de datos de la consulta. Según la forma de transmisión del VIH se establecieron dos grupos: vertical y horizontal. Se registró la manifestación inicial y la edad de presentación, así como la edad del diagnóstico VIH. Las frecuencias fueron comparadas por el método chi cuadrado. Se incluyeron 191 pacientes: grupo vertical 80,1 por ciento y grupo horizontal 19,9 por ciento. Del total 5,2 por ciento estaban asintomáticos, 33,5 por ciento tenían manifestaciones inespecíficos, 41,9 por ciento tenían síntomas VIH/no SIDA y 19,4 por ciento tenían síntomas VIH/SIDA. Las manifestaciones más frecuentes fueron: linfadenopatías generalizadas (25 por ciento), hepatomegalia (16,1 por ciento), infecciones respiratorias altas recurrentes y persistentes (15,1 por ciento), infecciones bacterianas severas (18,2 por ciento), diarrea crónica (11,4 por ciento) y esplenomegalia (10,9 por ciento). La edad de la primera manifestación fue de 0,9 ± 0,7 años en el grupo vertical y 5,5 ± 3,9 años en el grupo horizontal. La edad del diagnóstico VIH fue 2,8 ± 2,7 años en el grupo vertical y 7,6 ± 4,9 años en el grupo horizontal. Las manifestaciones inespecíficas fueron las más frecuentes: linfoadenopatías generalizadas, hepatomegalia e infecciones respiratorias altas. Sin embargo, las infecciones bacterianas severas y la diarrea crónica, constituyen manifestaciones relevantes para la sospecha de infección VIH. El diagnóstico se realizó como mínimo 2 años después de la primera manifestación en ambos grupos.

Pediatric HIV infection shows different manifestations whose recognition allows an early diagnostic approach. To determine the initial manifestations in HIV pediatric patients. It was a comparative and retrospective study that included HIV patients who attended to Hospital de Niños “J.M de Los Ríos” (Caracas, Venezuela), between 1987-2006. Data were obtained from HIV consultation Data Base. According to HIV transmission, we established two groups: vertical and horizontal. The initial manifestation and the patient age at that moment were recorded, so was the HIV diagnosis age. The frequencies were compared by square chi method. There were 191 patients: 80,1% in the vertical group and 19,9% in the horizontal one. There were 5,2% of asymptomatic patients, 33,5% had inespecific manifestations, 41,9% had HIV/no AIDS symptoms and 19,4% had HIV/AIDS symptoms. The most frequently seen manifestations were: generalized lymphadenopathy (25%), hepatomegaly (16%), recurrent and persistent upper respiratory tract infection (15,1%), severe bacterial infection (18,2%), chronic diarrhea (11,4%) and splenomegaly (10,9%). The age at the first manifestation was 0,9 ± 0,7 years in the vertical group and 5,5 ± 3,9 years in the horizontal one. The HIV diagnosis age was 2,8 ± 2,7 years in the vertical group and 7,6 ± 4,9 years in the horizontal one. The most frequent manifestations were inespecific: generalized lymphadenopathy, hepatomegaly and upper respiratory tract infection. However, severe bacterial infections and chronic diarrhea are relevant manifestations to suspect HIV infection. HIV diagnosis was done at least two years after the first manifestation in both groups.

Caracterización clínica de pacientes con neumonía nosocomial en las unidades de atención al grave / Clinical characterization of patients with nosocomial pneumonia in the acute care units

Se realizó un estudio descriptivo retrospectivo en el Hospital Clinicoquirúrgico Hermanos Ameijeiras, en el período comprendido entre el 1º de abril y el 31 diciembre de 2006 para hacer una caracterización clínica de los pacientes que adquirieron neumonía nosocomial en las unidades de atención al paciente grave. Se confeccionó un modelo de recogida de datos, los cuales se obtuvieron de las historias clínicas y de los protocolos de necropsias. Se efectuó el cálculo de porcentajes y la prueba de chi cuadrado de Pearson para el análisis de los datos. Se registraron 727 ingresos en ese período, y de ellos 107 (14,7 por ciento) adquirieron neumonía nosocomial. Se halló que el grupo de edad más afectado fue el de los mayores de 60 años (69,1 por ciento), el mayor porcentaje de enfermos fueron hombres (53,3 por ciento) y el 62,8 por ciento adquirió la neumonía en las primeras 72 h de estadía en la unidad. Se identificaron como más frecuentes, los antecedentes patológicos personales siguientes: hipertensión arterial (53,2 por ciento), diabetes mellitus (25,2 por ciento) y cardiopatía isquémica (19,6 por ciento). Hubo asociación estadísticamente significativa entre el uso de la ventilación mecánica y el fallecimiento de los pacientes (p= 0,001). No se halló asociación estadísticamente significativa entre los trastornos de la conciencia y el tiempo de estadía con el estado al egreso (p=0,77 y p=0,28, respectivamente). Se aislaron más frecuentemente los gérmenes: Staphylococcus aureus (62,5 por ciento), Acinetobacter (40,9 por ciento) y Klebsiella neumoniae (38,6 por ciento). Se concluyó que la causa directa de muerte en el 60,8 por ciento de los pacientes fue la neumonía nosocomial.

A descriptive and retrospective study was conducted in Hermanos Ameijeiras Clinical and Surgical Hospital from April 1 to December 31, 2006, to make a clinical characterization of the patients that acquired nosocomial pneumonia in the acute care units. A model to collect data was designed. The data were obtained from the medical histories and the necropsy protocols. The calculation of percentages and Pearson's chi square test were used to analyze data. 727 admissions were registered in that period, and 107 of them (14.7 percent) acquired nosocomial pneumonia. The group over 60 (69.1 percent) was the most affected. The highest percentage of sick individuals were males (53.3 percent), whereas 62.8 percent acquired pneumonia in the first 72 hours of stay at the unit. The following personal pathological histories were the most frequent: arterial hypertension (53.2 percent), diabetes mellitus (25.2 percent) and ischemic heart disease (19.6 percent). There was a statistically significant association between the use of mechanical ventilation and the patients' death (P 0.001). No marked statistically association was found between the consciousness disorders and the stay length with the state on discharge (p 0.77 and p 0.28, respectively). Staphylococcus aureus (62.5 percent), acinetobacter (40.9 percent) and Klebsiella neumoniae (38.6 percent) were the most frequently isolated germs. It was concluded that nosocomial pneumonia was the direct cause of death in 60.8 percent of the patients.

Estudo comparativo entre pacientes idosos internados com diagnóstico clínico de pneumonia comunitária, com ou sem confirmação radiológica / Comparative study of elderly inpatients clinically diagnosed with community-acquired pneumonia, with or without radiological confirmation

OBJETIVOS: Comparar aspectos clínicos, radiológicos e evolutivos de idosos internados com diagnóstico clínico de pneumonia comunitária, com ou sem confirmação radiológica. MÉTODOS: Foram estudados, retrospectivamente, 141 pacientes com idade acima de 60 anos. RESULTADOS: Em 45 pacientes, os achados radiológicos corroboraram o diagnóstico clínico e, em 96 pacientes, a radiologia não foi compatível com a suspeita clínica. Os sinais, os sintomas, a terapêutica e os desfechos destes dois grupos foram comparados. Os achados do estudo sugerem que não houve diferença significativa entre os grupos segundo os critérios analisados. A prevalência de radiografias de tórax compatíveis com pneumonia entre pacientes com suspeita clínica da doença foi de pouco mais de 30 por cento. CONCLUSÃO: O diagnóstico clínico de pneumonia comunitária tem baixa especificidade em idosos e deve ser usado com cautela. Devido ao pequeno número de pacientes estudados, mais estudos sobre o tema são necessários para confirmar os achados.

OBJECTIVES: To compare clinical and radiological aspects, as well as aspects regarding the course of the disease, of elderly inpatients clinically diagnosed with community-acquired pneumonia, with or without radiological confirmation. METHODS: A total of 141 patients over the age of 60 were retrospectively studied. RESULTS: Radiological findings corroborated the clinical diagnosis in 45 patients, whereas, in 96 patients, radiology did not correlate with the clinical suspicion. The signs, symptoms, treatment, and outcomes of these two groups were compared. The findings of the study suggest that there were no significant differences between the groups according to the criteria analyzed. CONCLUSION: The prevalence of chest X-rays compatible with pneumonia in patients suspected of the disease was slightly higher than 30 percent. Having low specificity in the elderly, the clinical diagnosis of community-acquired pneumonia should be used with caution. In view of the small number of patients studied, further studies on this topic are needed in order to confirm the findings.

Ventilator associated pneumonia: the role of typical, atypical bacteria and fungi; comparison between endotracheal aspirate and bronchoalveolar lavage

Ventilator associated pneumonia [VAP] is defined as pneumonia occurring after the first 48 hours of starting mechanical ventilation. The incidence of VAP varied between 7-70% in different studies. The pathogenesis of VAP usually requires the occurrence of two important processes: bacterial colonization of the aerodigestive tract and the aspiration of contaminated secretion into the normally sterile lower respiratory tract. The principal promise of bronchoscopy for the diagnosis consists of the ability to retrieve uncontaminated lower respiratory secretions and consequently doing quantitative cultures, this should allow a valid differentiation of colonization from infection. The aim of this study was to determine the role of legionella species, mycoplasma pneumoniae, Chlamydia pneumoniae, mycobacterium tuberculosis, fungi, and anaerobes as etiologic agents of VAP and to compare between quantitative Endotracheal Aspirate [EA] and bronchoalveolar lavage[BAL] techniques for the diagnosis of VAP. The study was conducted on 30 patients admitted to the critical care medicine department of Alexandria main university hospital who required invasive mechanical ventilation for at least 48 hours and developed clinical manifestations of VAP. Gram negative bacteria were the most common etiologic pathogens, followed by atypical bacteria. There was no statistically significant difference between both EA and BAL regarding the aetiologic pathogens

Evaluación de la gravedad en la neumonía del adulto adquirida en la comunidad / Evluating severiity of community-acquired pneumonia inaddults

Clinical evolution in patients affected by community acquired pneumonia varies from a mild and low risk infectious disease to an extremely severe, life threatening disease. Commonly, immunocompetent adults without co-morbidities or severe risk factors cared for at out patient clinic have low risk of complications and death (mortality below 1-2%); it increases to 5-15% in patients with co-morbidities and/or with specific risk factors that are admitted into the hospital and reaches 20-50% in those patients admitted into ICUs. Evaluation of severity in patients with pneumonia allows the prediction of disease evolution, establishing the proper setting of care, the type- of microbiological tests needed, and to choose the best empiric antibiotic treatment. It is suggested that patients be in three risk categories: low risk (mortality under 1-2%) susceptible to ambulatory treatment; high risk patients (mortality 20-30%) that need specialized wards; and intermediate risk patients, with co-morbidities and/or risk factors for complicated clinical evolution and death, but cannot be classified in a specific category. In the ambulatory setting, without availability of complete laboratory exams, it is recommended to evaluating the severity of pneumonia considering the following clinical variables: age over 65 years, presence of co-morbidities, sensorial compromise, vital signs alteration, degree of radiological involvement: multilobar, bilateral findings, cavitations), pleural effusion and arterial oximetry < 90%. However, clinical judgement and the physician´s experience must predominate over predictive models, which are not infallible.

La evolución del paciente con neumonía adquirida en la comunidad puede variar entre un cuadro infeccioso banal de bajo riesgo de complicaciones hasta uno de extrema gravedad con riesgo vital. En general, el adulto inmunocompetente sin co-morbilidad ni criterios de gravedad manejado en el medio ambulatorio tiene bajo riesgo de complicaciones y muerte (letalidad menor de 1-2%), elevándose a 5-15% en los pacientes con co-morbilidad y/o factores de riesgo específicos que son admitidos al hospital y a 20-50% en aquellos admitidos a la Unidad de Cuidados Intensivos. La evaluación de la gravedad en el paciente con neumonía permite predecir la evolución de la enfermedad, orientar el lugar de manejo, la extensión del estudio microbiológico, y el tratamiento antimicrobiano empírico. Se sugiere clasificar a los enfermos en tres categorías de riesgo: pacientes con bajo riesgo (mortalidad inferior a 1-2%) susceptibles de tratamiento ambulatorio; pacientes con alto riesgo (mortalidad entre 20-30%) que deben ser manejados en unidades especializadas del hospital; y pacientes con riesgo intermedio, con co-morbilidad y/o factores de riesgo de evolución complicada y muerte, pero que no es posible clasificar en una categoría precisa. En el medio ambulatorio, donde no se dispone de exámenes complementarios, se recomienda evaluar la gravedad de los pacientes con neumonía considerando las siguientes variables clínicas: edad sobre 65 años, presencia de co-morbilidad, compromiso de conciencia, alteración de los signos vitales, compromiso radiográfico multilobar o bilateral, presencia de cavitación o efusión pleural, y SaO2 < 90%. Sin embargo, el juicio clínico y la experiencia del médico deben predominar sobre los modelos predictores, los cuales no son infalibles.