Anti-inflammatory mechanisms and pharmacological actions of phycocyanobilin in a mouse model of experimental autoimmune encephalomyelitis: A therapeutic promise for multiple sclerosis.

Cytokines, demyelination and neuroaxonal degeneration in the central nervous system are pivotal elements implicated in the pathogenesis of multiple sclerosis (MS) and its nonclinical model of experimental autoimmune encephalomyelitis (EAE). Phycocyanobilin (PCB), a chromophore of the biliprotein C-Phycocyanin (C-PC) from Spirulina platensis, has antioxidant, immunoregulatory and anti-inflammatory effects in this disease, and it could complement the effect of other Disease Modifying Treatments (DMT), such as Interferon-ß (IFN-ß). Here, our main goal was to evaluate the potential PCB benefits and its mechanisms of action to counteract the chronic EAE in mice. MOG35-55-induced EAE was implemented in C57BL/6 female mice. Clinical signs, pro-inflammatory cytokines levels by ELISA, qPCR in the brain and immunohistochemistry using precursor/mature oligodendrocytes cells antibodies in the spinal cord, were assessed. PCB enhanced the neurological condition, and waned the brain concentrations of IL-17A and IL-6, pro-inflammatory cytokines, in a dose-dependent manner. A down- or up-regulating activity of PCB at 1 mg/kg was identified in the brain on three (LINGO1, NOTCH1, and TNF-α), and five genes (MAL, CXCL12, MOG, OLIG1, and NKX2-2), respectively. Interestingly, a reduction of demyelination, active microglia/macrophages density, and axonal damage was detected along with an increase in oligodendrocyte precursor cells and mature oligodendrocytes, when assessed the spinal cords of EAE mice that took up PCB. The studies in vitro in rodent encephalitogenic T cells and in vivo in the EAE mouse model with the PCB/IFN-ß combination, showed an enhanced positive effect of this combined therapy. Overall, these results demonstrate the anti-inflammatory activity and the protective properties of PCB on the myelin and support its use with IFN-ß as an improved DMT combination for MS.

Impact of an ultrasound-driven diagnostic protocol at early intensive-care stay: a randomized-controlled trial.

BACKGROUND: Point-of-care ultrasound (POCUS) is a tool in increasing use, but there is still a lack of basics for its routine use and evidence of its impact in intensive care. OBJECTIVE: To measure the impact of POCUS on resource utilization, diagnostic accuracy, and clinical management in medical-surgical intensive care units (ICUs). METHODS: Prospective, controlled study, in two polyvalent ICUs. The patients were randomly assigned to POCUS or control group. INTERVENTIONS: POCUS patients received systematic ultrasound examination of optic nerve, lung/pleura, heart, abdomen, and venous system, performed at the bedside by trained intensivists. Control patients were treated by critical care specialists who do not perform ultrasound in their clinical practice. RESULTS: We included 80 patients, 40 per group. There were no significant differences in age, sex, APACHE II score, or admission diagnosis. POCUS group used fewer resources per patient in the first 5 days of hospitalization: chest radiography (2.6 ± 2.0 vs 4.1 ± 3.5, P = 0.01), additional ultrasound evaluations performed by a radiology specialist (0.6 ± 0.7 vs 1.1 ± 0.7, P = 0.002), and computed tomography studies (0.5 ± 0.6 vs 0.9 ± 0.7, P = 0.007). Time to perform any requested ultrasound evaluation after ICU admission was 2.1 ± 1.6 h versus 7.7 ± 6.7 h (P = 0.001). Systematic ultrasound evaluation led to better characterization of ICU admission diagnosis in 14 (35%) patients and change in clinical management in 24 (60%). POCUS group had lower fluid balance at 48 and 96 h after admission (P = 0.01) and spent less time mechanically ventilated (5.1 ± 5.7 days vs 8.8 ± 9.4, P = 0.03). CONCLUSIONS: Systematic application of POCUS may decrease utilization of conventional diagnostic imaging resources and time of mechanical ventilation, and facilitate meticulous intravenous fluid administration in critically ill patients during the first week of stay in the ICU. Trial registration ClinicalTrials.gov Identifier: NCT03608202.

Delirium in a Latin American intensive care unit. A prospective cohort study of mechanically ventilated patients. / Delirium em uma unidade de terapia intensiva latino-americana. Estudo prospectivo em coorte em pacientes em ventilação mecânica.

OBJECTIVE: To establish the prevalence of delirium in a general intensive care unit and to identify associated factors, clinical expression and the influence on outcomes. METHODS: This was a prospective cohort study in a medical surgical intensive care unit. The Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit were used daily to identify delirium in mechanically ventilated patients. RESULTS: In this series, delirium prevalence was 80% (N = 184 delirious patients out of 230 patients). The number of patients according to delirium psychomotor subtypes was as follows: 11 hyperactive patients (6%), 9 hypoactive patients (5%) and 160 mixed patients (89%). Multiple logistic regression modeling using delirium as the dependent outcome variable (to study the risk factors for delirium) revealed that age > 65 years, history of alcohol consumption, and number of mechanical ventilation days were independent variables associated with the development of delirium. The multiple logistic regression model using hospital mortality as the dependent outcome variable (to study the risk factors for death) showed that severity of illness, according to the Acute Physiology and Chronic Health Evaluation II, mechanical ventilation for more than 7 days, and sedation days were all independent predictors for excess hospital mortality. CONCLUSION: This Latin American prospective cohort investigation confirmed specific factors important for the development of delirium and the outcome of death among general intensive care unit patients. In both analyses, we found that the duration of mechanical ventilation was a predictor of untoward outcomes.

OBJETIVO: Estabelecer a prevalência do delirium em uma unidade de terapia intensiva geral e identificar os fatores associados, sua expressão clínica e sua influência no desfecho. MÉTODOS: Trata-se de um estudo prospectivo de coorte em uma unidade de terapia intensiva clínico-cirúrgica. Avaliamos os pacientes diariamente, com a Richmond Agitation-Sedation Scale e a Confusion Assessment Method for the Intensive Care Unit, com o objetivo de identificar delirium nos pacientes mecanicamente ventilados. RESULTADOS: Nesta série de casos, a prevalência de delirium foi de 184 pacientes com delirium em um total de 230 pacientes. O subtipo de delirium psicomotor foi hiperativo em 11 pacientes (6%), hipoativo em 9 (5%) e misto em 160 (89%). Uma modelagem de regressão logística múltipla, com delirium como a variável de desfecho dependente (para avaliar os fatores de risco para delirium), revelou que idade acima de 65 anos, histórico de consumo de álcool e dias em uso de ventilação mecânica foram variáveis que se associaram independentemente com o desenvolvimento de delirium. Um modelo de regressão logística múltipla, que utilizou mortalidade hospitalar como variável de desfecho dependente (para estudar os fatores de risco para óbito), mostrou que o índice de severidade da doença, como o aferido segundo o escore Acute Physiology and Chronic Health Evaluation II, o uso de ventilação mecânica por mais de 7 dias e o número de dias de sedação foram as dependentes preditoras de mortalidade hospitalar mais elevada. CONCLUSÃO: Este estudo latino-americano de coorte confirmou os fatores específicos importantes para delirium e o desfecho óbito entre pacientes admitidos a uma unidade de terapia intensiva geral. Em ambas as análises, identificamos que a duração da ventilação mecânica é um preditor de desfechos desfavoráveis.

Delirium em uma unidade de terapia intensiva latino-americana. Estudo prospectivo em coorte em pacientes em ventilação mecânica / Delirium in a Latin American intensive care unit. A prospective cohort study of mechanically ventilated patients

RESUMO Objetivo: Estabelecer a prevalência do delirium em uma unidade de terapia intensiva geral e identificar os fatores associados, sua expressão clínica e sua influência no desfecho. Métodos: Trata-se de um estudo prospectivo de coorte em uma unidade de terapia intensiva clínico-cirúrgica. Avaliamos os pacientes diariamente, com a Richmond Agitation-Sedation Scale e a Confusion Assessment Method for the Intensive Care Unit, com o objetivo de identificar delirium nos pacientes mecanicamente ventilados. Resultados: Nesta série de casos, a prevalência de delirium foi de 184 pacientes com delirium em um total de 230 pacientes. O subtipo de delirium psicomotor foi hiperativo em 11 pacientes (6%), hipoativo em 9 (5%) e misto em 160 (89%). Uma modelagem de regressão logística múltipla, com delirium como a variável de desfecho dependente (para avaliar os fatores de risco para delirium), revelou que idade acima de 65 anos, histórico de consumo de álcool e dias em uso de ventilação mecânica foram variáveis que se associaram independentemente com o desenvolvimento de delirium. Um modelo de regressão logística múltipla, que utilizou mortalidade hospitalar como variável de desfecho dependente (para estudar os fatores de risco para óbito), mostrou que o índice de severidade da doença, como o aferido segundo o escore Acute Physiology and Chronic Health Evaluation II, o uso de ventilação mecânica por mais de 7 dias e o número de dias de sedação foram as dependentes preditoras de mortalidade hospitalar mais elevada. Conclusão: Este estudo latino-americano de coorte confirmou os fatores específicos importantes para delirium e o desfecho óbito entre pacientes admitidos a uma unidade de terapia intensiva geral. Em ambas as análises, identificamos que a duração da ventilação mecânica é um preditor de desfechos desfavoráveis.

ABSTRACT Objective: To establish the prevalence of delirium in a general intensive care unit and to identify associated factors, clinical expression and the influence on outcomes. Methods: This was a prospective cohort study in a medical surgical intensive care unit. The Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit were used daily to identify delirium in mechanically ventilated patients. Results: In this series, delirium prevalence was 80% (N = 184 delirious patients out of 230 patients). The number of patients according to delirium psychomotor subtypes was as follows: 11 hyperactive patients (6%), 9 hypoactive patients (5%) and 160 mixed patients (89%). Multiple logistic regression modeling using delirium as the dependent outcome variable (to study the risk factors for delirium) revealed that age > 65 years, history of alcohol consumption, and number of mechanical ventilation days were independent variables associated with the development of delirium. The multiple logistic regression model using hospital mortality as the dependent outcome variable (to study the risk factors for death) showed that severity of illness, according to the Acute Physiology and Chronic Health Evaluation II, mechanical ventilation for more than 7 days, and sedation days were all independent predictors for excess hospital mortality. Conclusion: This Latin American prospective cohort investigation confirmed specific factors important for the development of delirium and the outcome of death among general intensive care unit patients. In both analyses, we found that the duration of mechanical ventilation was a predictor of untoward outcomes.

Meningoencefalitis por Streptococcus suis.: Primeros dos casos en Uruguay. / Streptococcus suis meningoencephalitis: First two cases reported in Uruguay

La infección por Streptococcus suis (S. suis) es una zoonosis emergente, poco frecuente, secundaria a la exposición alimentaria o laboral a cerdos. La infección en los humanos se considera una enfermedad emergente con aparición de casos esporádicos, y más raramente brotes. Son un importante problema en la industria porcina a nivel mundial, ya que coloniza los tractos respiratorios, digestivo y genital del ganado porcino, siendo éstos portadores asintomáticos en 80% de los casos. En el humano S. suis causa una infección sistémica que puede afectar varios órganos. La meningitis es la manifestación más frecuente (68%); con menor frecuencia puede causar sepsis (25%), artritis (12,9%), endocarditis (12,4%) y endoftalmitis (4,6%). El tratamiento de elección para la meningitis a S. suis es la penicilina. En esta comunicación se presentan los primeros dos casos de meningoencefalitis causada por S. suis en Uruguay en 2008 y 2009. Un tercer caso se reportó en Paysandú en 2009.

Infection with Streptococcus suis (S. suis) is an uncommon emerging zoonosis, secondary to food or occupational exposure to pigs. Infection in humans is considered an emerging disease with onset of sporadic cases and outbreaks rarely. They are a major problem in the swine industry worldwide since colonizes the respiratory, digestive and genital tracts of pigs, they remain asymptomatic carriers in 80% of cases. In the human S. suis causes a systemic infection that can affect various organs. Meningitis is the most common presentation (68%), less often can cause sepsis (25%), arthritis (12.9%), endocarditis (12.4%) and endophthalmitis (4.6%). The treatment of choice for S suis meningitis is penicillin. In this communication the first two cases of meningoencephalitis caused by S. suis in Uruguay in 2008 and 2009. A third case was reported in Paysandú in 2009.

Neumonía asociada a la ventilación. Incidencia, agentes etiológicos y evolución según tipo de tratamiento / Ventilator-associated pneumonia. Incidence, etiologic agents and evolution depending on type of treatment

Los objetivos del presente trabajo fueron: 1) valorar la incidencia, microbiología y evolución de la neumonía asociada a la ventilación (NAV) y 2) evaluar la curación y mortalidad de la NAV según el tipo de tratamiento antimicrobiano: empírico o específico. Este estudio prospectivo y observacional se realizó en nuestra unidad de cuidados intensivos durante un período de 10 meses. Se diagnosticaron 63 episodios de NAV en 60 pacientes. La tasa ajustada al tiempo de ventilación mecánica fue 25,8 episodios/1.000 días. Pseudomonas aeruginosa, Acinetobacter baumannii y Staphylococcus aureus fueron los microorganismos más frecuentes y se aislaron en 42 oportunidades sobre un total de 67 aislamientos. Se trataron 49 episodios de NAV de los cuales curaron 27 (55 por ciento) y no curaron 22 (45 por ciento). Se realizó tratamiento específico en 17 casos (34,7 por ciento), tratamiento empírico correcto en 22 (44,9 por ciento) y tratamiento empírico incorrecto en 6 casos de NAV (12,2 por ciento); el tratamiento empírico falló en seis de las 28 NAV tratadas empíricamente (21 por ciento). Cuando se hizo tratamiento específico curaron 11 NAV y no curaron seis. Con tratamiento empírico correcto curaron 14 NAV y no curaron ocho (p: NS). Cuando el tratamiento empírico fue incorrecto no curó ninguna de las seis NAV (p: 0,015). La mortalidad cruda fue de 56 por ciento (n:94) para la poblacion sin NAV y de 68,2 por ciento (n:43) para la población con NAV, p<0.05. La mortalidad relacionada fue de 28 (44,4 por ciento). Con el tratamiento empírico correcto murieron seis pacientes y sobrevivieron 11, con el tratamiento empírico incorrecto murieron 5 pacientes y no sobrevivió ninguno (p: 0,035). Conclusiones: 1) Existió alta incidencia de NAV; 2) los pacientes con NAV se relacionaron con mayor mortalidad; 3) Pseudomonas aeruginosa, Acinetobacter baumannii y Staphylococcus aureus fueron los microorganismos predominantes; 4) no hubo diferencias significativas en la curación y en la mortalidad relacionada cuando se comparó tratamiento específico vs tratamiento empírico correcto; 5) la falla del tratamiento empírico resultó en 21 por ciento