Effects of early hemodynamic resuscitation on left ventricular performance and microcirculatory function during endotoxic shock.

BACKGROUND: Microcirculation and macrohemodynamics are severely compromised during septic shock. However, the relationship between these two compartments needs to be further investigated. We hypothesized that early resuscitation restores left ventricular (LV) performance and microcirculatory function but fails to prevent metabolic disorders. We studied the effects of an early resuscitation protocol (ERP) on LV pressure/volume loops-derived parameters, sublingual microcirculation, and metabolic alterations during endotoxic shock. METHODS: Twenty-five pigs were randomized into three groups: LPS group: Escherichia coli lipopolysaccharide (LPS); ERP group: LPS + ERP based on volume expansion, dobutamine, and noradrenaline infusion; Sham group. LV pressure/volume-derived parameters, systemic hemodynamics, sublingual microcirculation, and metabolic profile were assessed at baseline and after completing the resuscitation protocol. RESULTS: LPS significantly decreased LV end-diastolic volume, myocardial contractility, stroke work, and cardiac index (CI). Early resuscitation preserved preload, and myocardial contractility, increased CI and heart rate (p < .05). LPS severely diminished sublingual microvascular flow index (MFI), perfused vascular density (PVD), and the proportion of perfused vessels (PPV), while increased the heterogeneity flow index (HFI) (p < .05). Despite MFI was relatively preserved, MVD, PVD, and HFI were significantly impaired after resuscitation (p < .05). The macro- and microcirculatory changes were associated with increased lactic acidosis and mixed venous O2 saturation when compared to baseline values (p < .05). The scatter plot between mean arterial pressure (MAP) and MFI showed a biphasic relationship, suggesting that the values were within the limits of microvascular autoregulation when MAP was above 71 ± 6 mm Hg (R (2) = 0.63). CONCLUSIONS: Early hemodynamic resuscitation was effective to restore macrohemodynamia and myocardial contractility. Despite MAP and MFI were relatively preserved, the persistent microvascular dysfunction could explain metabolic disorders. The relationship between micro- and systemic hemodynamia and their impact on cellular function and metabolism needs to be further studied during endotoxic shock.

Effect of pneumococcal conjugate vaccination in Uruguay, a middle-income country.

BACKGROUND: In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance. METHODS: Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children < 2 years and 2 to 4 years old, and patients ≥ 5 years old. Trends of frequency for each serotype were also analyzed. RESULTS: Comparison of pre-vaccination (2003-2007) and post-vaccination (2008-2012) periods showed a significant decrease in IPD incidence among children < 2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p < 0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ≥ 5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33. CONCLUSION: Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children < 5 years of age in Uruguay.

Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1ß was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.

Medicina genómica aplicada a la neumonía aguda comunitaria: [revisión] / Genomic medicine applied to acute community acquired pneumonia: [review]

Las infecciones del tracto respiratorio inferior constituyen un enorme flagelo para la humanidad. La neumonía aguda comunitaria es la principal enfermedad respiratoria por frecuencia y severidad. A pesar de los avances de la medicina moderna, su morbilidad y mortalidad permanecen prácticamente incambiadas.La respuesta ante un agravio infeccioso es estrictamente individual al estar influida por la estructura genética del huésped. La medicina genómica procura personalizar y optimizar el diagnóstico, pronóstico y tratamiento mediante el reconocimiento de la influencia que ejercen determinadas variantesgenéticas, denominadas polimorfismos, en la susceptibilidad y evolución de las diversas patologías. Los polimorfismos genéticos son capaces de modificar el riesgo de padecer determinadoevento o suceso en una enfermedad específica por lo cual su reconocimiento permite personalizar la interacción entre ambiente y huésped. En el presente artículo se describen los polimorfismos que están asociados positivamente conla evolución de la neumonía aguda comunitaria y qué aplicaciones clínicas podría tener la medicina genómica.

As infecções do trato respiratório inferior são um importante problema para a humanidade sendo a pneumonia aguda comunitária a principal doença respiratória por sua frequência e gravidade. Apesar dos avanços da medicina moderna sua morbidade e mortalidade permanecem praticamente inalteradas. A resposta ante um ataque infeccioso é estritamente individual por estar sujeita à estrutura genética do hóspede. A medicina genômica busca personalizar e otimizar o diagnóstico,prognóstico e tratamento reconhecendo a influencia que exercem determinadas variantes genéticas, denominadas polimorfismos, sobre a suscetibilidade e a evolução das diferentes patologias.Os polimorfismos genéticos são capazes de modificar o risco de sofrer determinado evento em uma doença específica pelo qual seu reconhecimento permite personalizar a interação entre ambiente e hóspede. Neste artigo os polimorfismos que estão associados positivamente com a evolução da pneumonia aguda comunitária e as possíveis aplicações clínicas da medicina genômica são descritos.

Lower respiratory tract infections constitute a serious problem for humanity. Community-acquired pneumonia is the main respiratory disease due to frequency and severity. Inspite of progress made by modern medicine, mortality and morbility rates remain unchanged. Response to an infectious attack is strictly personal as it is influenced by the hostÆs genetic structure. Genomic medicine aims to personalize and optimize diagnosis, prognosis and treatment by acknowledging the influence of certain genetic variations, called polymorphisms,on susceptibility and the evolution of several pathologies. Genetic polymorphisms are able to modify the risk of suffering a certain event or episode in a specific disease and being aware of this enables personalizing the interaction between the environment and the host. The present study describes polymorphisms that are positively associated to the evolution of acute-community acquired pneumoniaand the possible clinical applications by genomic medicine.

Clinical characteristics and outcomes of patients with 2009 influenza A(H1N1) virus infection with respiratory failure requiring mechanical ventilation.

PURPOSE: The purpose of the study was to describe the clinical characteristics and outcomes of critically ill patients with 2009 influenza A(H1N1). METHODS: An observational study of patients with confirmed or probable 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation was performed. RESULTS: We studied 96 patients (mean age, 45 [14] years [mean, SD]; 44% female). Shock and acute respiratory distress syndrome were diagnosed during the first 72 hours of admission in 43% and 72% of patients, respectively. Noninvasive positive pressure ventilation was used in 45% of the patients, but failed in 77% of them. Bacterial pneumonia was diagnosed in 33% of cases, 8% during the first week (due to community-acquired microorganisms) and 25% after the first week (due to gram-negative bacilli and resistant gram-positive cocci). Intensive care unit mortality was 50%. Nonsurvivors differed from survivors in the prevalence of cardiovascular, respiratory, and hematologic failure on admission and late pneumonia. Reported causes of death were refractory hypoxia, multiorgan failure, and shock (50%, 38%, and 12% of all causes of death, respectively). CONCLUSIONS: Patients with 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation often present with clinical criteria of acute respiratory distress syndrome and shock. Bacterial pneumonia is a frequent complication. Mortality is high and is primarily due to refractory hypoxia.

Meningitis y encefalitis víricas en Uruguay. Relevamiento mediante técnicas de reacción en cadena de polimerasa aplicadas al líquido cefalorraquídeo de los grupos herpes, enterovirus y arbovirus como principalesagentes etiológicos: a propósito de 59 casos / Meningitis and viral encephalitis in Uruguay. Survey through polymerase chain reaction (PCR) on cerebrospinal fluid for herpesvirus, enterovirus and arbovirus as main etiological agents: 59 cases studied

Introducción: en nuestro país no existen trabajos sistemáticos relativos a la incidencia de virus que provoquen encefalitis y meningitis. Sí existen trabajos realizados en las décadas de1960 y 1970 sobre seroprevalencia de arbovirus y poliovirus. Mediante la técnica de reacción en cadena de polimerasa (PCR) aplicada al líquidocefalorraquídeo (LCR) hoy es posible realizar en un breve lapso de tiempo un diagnóstico de certeza sobre diversos agentes virales responsables de estas neurovirosis. Material y métodos: se exploró la incidencia de virus de la familia herpes, enterovirus y grupoarbovirus mediante técnicas de PCR aplicadas al LCR en pacientes VIH negativos. Resultados: este trabajo presenta a 59 pacientes VIH negativos que padecieron encefalitis ymeningitis de presumible etiología viral. Estos agentes son los responsables de la mayor cantidad de meningitis y encefalitis que suceden en nuestro continente. Conclusiones: el diagnóstico virológico final es posible realizarlo en más de la mitad de los casos presentados, predominando virus de la familia herpes tanto en niños como en adultos, no siendo despreciable la incidencia de enterovirus. No se detectó en este trabajo la presencia de arbovirus.

Introduction: in our country there are no systematic studies on the incidence of virus as a cause of encephalitis and meningitis. However, some studies on the seroprevalence of arbovirus and poliovirus were carried out in the sixties and seventies. Today, the polymerasechain reaction (PCR) applied to cerebrospinal fluid technique allows us to obtain accurate diagnosis within a short time, on the different viral agents that cause these neuroviroses.Method: we explored the incidence of virus from the herpesvirus, enterovirus and arbovirus group through PCRtechniques applied to HIV negative patients. Results: this study included 59 HIV negative patients who suffered from encephalitis and meningitis of viral etiology. These agents are responsible for most of the cases of meningitis and encephalitis in our continent.Conclusions: the final viral diagnosis may be obtained in over half of the cases presented. The herpesvirus is themost frequent both in children and in adults, being it significant the incidence of enterovirus. No arbovirus wereidentified in this study.

Introdução: no nosso país não existem estudos sistemáticos relativos à incidência de vírus que provoquemencefalites e meningites. Existem trabalhos realizados nas décadas de 1960 e 1970 sobre a soroprevalência dearbovírus e de poliovirus. Utilizando a técnica de reação em cadeia da polimerase (PCR) no líquido cefalorraquidiano (LCR) é possível realizar, em pouco tempo, um diagnóstico de certeza sobre diversosagentes virais responsáveis por estas neuroviroses. Material e métodos: buscou-se determinar a incidênciade vírus das famílias herpes, enterovírus e grupo arbovírus pelas técnicas de PCR no LCR de pacientes VIH negativos.Resultados: este trabalho apresenta 59 pacientes VIH negativos que tiveram encefalite ou meningite com provável etiologia viral. Estes agentes são responsáveis pelo maior número de casos de meningite e encefalite nonosso continente. Conclusões: em mais da metade dos casos apresentadosfoi possível realizar o diagnóstico virológico final; registrou-se uma predominância dos vírus da família herpes tanto em crianças como em adultos sendo que a incidência de enterovírus não era desprezível. Não se detectou a presença de arbovirus.