Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations

BACKGROUND: Chronic alcohol consumption is associated with neuroinflammation, neuronal damage, and behavioral alterations including addiction. Alcohol-induced neuroinflammation is characterized by increased expression of proinflammatory cytokines (including TNFalpha, IL-1beta, and CCL2) and microglial activation. We hypothesized chronic alcohol consumption results in peripheral immune cell infiltration to the CNS. Since chemotaxis through the CCL2-CCR2 signaling axis is critical for macrophage recruitment peripherally and centrally, we further hypothesized that blockade of CCL2 signaling using the dual CCR2/5 inhibitor cenicriviroc (CVC) would prevent alcohol-induced CNS infiltration of peripheral macrophages and alter the neuroinflammatory state in the brain after chronic alcohol consumption. METHODS: C57BL/6J female mice were fed an isocaloric or 5% (v/v) ethanol Lieber DeCarli diet for 6 weeks. Some mice received daily injections of CVC. Microglia and infiltrating macrophages were characterized and quantified by flow cytometry and visualized using CX3CR1(eGFP/+) CCR2(RFP/+) reporter mice. The effect of ethanol and CVC treatment on the expression of inflammatory genes was evaluated in various regions of the brain, using a Nanostring nCounter inflammation panel. Microglia activation was analyzed by immunofluorescence. CVC-treated and untreated mice were presented with the two-bottle choice test. RESULTS: Chronic alcohol consumption induced microglia activation and peripheral macrophage infiltration in the CNS, particularly in the hippocampus. Treatment with CVC abrogated ethanol-induced recruitment of peripheral macrophages and partially reversed microglia activation. Furthermore, the expression of proinflammatory markers was upregulated by chronic alcohol consumption in various regions of the brain, including the cortex, hippocampus, and cerebellum. Inhibition of CCR2/5 decreased alcohol-mediated expression of inflammatory markers. Finally, microglia function was impaired by chronic alcohol consumption and restored by CVC treatment. CVC treatment did not change the ethanol consumption or preference of mice in the two-bottle choice test. CONCLUSIONS: Together, our data establish that chronic alcohol consumption promotes the recruitment of peripheral macrophages into the CNS and microglia alterations through the CCR2/5 axis. Therefore, further exploration of the CCR2/5 axis as a modulator of neuroinflammation may offer a potential therapeutic approach for the treatment of alcohol-associated neuroinflammation

Acurácia dos indicadores de mortalidade devido a sepse dos óbitos ocorridos no Distrito Federal

Background: Sepsis currently represents a challenge for health systems, this fact may be related to the spread of bacterial resistance, the increase in the population of elderly, immunosuppressed individuals, and the improvement of emergency care, favoring the survival of critically ill patients. This article aimed to evaluate the accuracy of mortality indicators due to sepsis in 2018. Method: Validation study of death certificates that occurred in the Federal District in 2018. Declarations whose basic causes of death identified were classified as garbage codes were identified, which were investigated by a multidisciplinary team, capable of reclassifying them with codes that allow for the improvement of health data. In order to assess accuracy, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of death certificates from sepsis were calculated, with 95% confidence intervals. Results: A total of  6.244 statements were evaluated, of which 233 (3.74%) presented sepsis as the underlying cause before being investigated and only 35 (0.56%) maintained it after the investigation. The filling of statements with sepsis as the underlying cause by physicians showed a sensitivity of 0.9% (95%CI: 0.6 to 1.3) and a specificity of 92.0% (95%CI: 90.9 to 93.1). Conclusion: The low accuracy of the declarations demonstrates the non-reliability of the underlying cause of death from sepsis, especially the completion of death certificates that occurred in the Federal District in 2018.  Justificación: Sepsis representa en la actualidad un desafío para los sistemas de salud, este hecho puede estar relacionado con propagación de resistencias bacterianas, aumento de la población de ancianos, inmunodeprimidos, y mejora de la atención de urgencias, favoreciendo la supervivencia de los pacientes críticos. Este artículo tuvo como objetivo evaluar la precisión de los indicadores de mortalidad por sepsis en 2018. Método: Estudio de validación de causa básica de muertes ocurridas en Distrito Federal en 2018. Se identificaron actas de defunción cuyas causas básicas de muerte fueron clasificadas como sepsis código basura y fueron investigadas por un equipo multidisciplinario capacitado para reclasificarlas con códigos que permitan la mejora de datos de salud. Para evaluar la precisión, se calcularon sensibilidad, especificidad, valores predictivos positivo y negativo y razones de verosimilitud positiva y negativa de certificados de defunción por sepsis, con intervalos de confianza del 95%. Resultados: se evaluaron 6.244 declaraciones, de las cuales 233 (3,74%) tenían como causa básica la sepsis antes de ser investigadas y solo 35 (0,56%) mantuvieron después de investigación. Realización de declaraciones con sepsis como causa subyacente por parte de los médicos mostró sensibilidad del 0,9% (95%IC: 0,6 a 1,3) y especificidad del 92,0% (95%IC: 90,9 a 93,1). Conclusión: Baja precisión de las declaraciones demuestra la poca confiabilidad de la causa subyacente de muerte por sepsis, especialmente la finalización de los certificados de defunción ocurridos en Distrito Federal en 2018.Justificativa: A sepse, atualmente, representa um desafio para os sistemas de saúde, tal fato pode estar relacionado com a disseminação da resistência bacteriana, o aumento da população de idosos, os indivíduos imunossuprimidos, e a melhoria do atendimento de emergência, favorecendo a sobrevivência de pacientes críticos. Este artigo teve por objetivo avaliar a acurácia dos indicadores de mortalidade devido à sepse em 2018. Método: Estudo de validação da causa básica dos óbitos ocorridos no Distrito Federal em 2018. Foram identificadas as declarações de óbito cujas causas básicas de morte apontadas foram classificadas como garbage code sepse, as quais foram investigadas por uma equipe multidisciplinar, capacitada para reclassificá-las com códigos que permitem o aprimoramento dos dados em saúde. A fim de avaliar a acurácia, foram calculados os valores de sensibilidade, especificidade, valores preditivos positivo e negativo, razões de verossimilhança positiva e negativa das declarações dos óbitos por sepse, com intervalos de confiança de 95%. Resultados: Um total de 6.244 declarações foram avaliadas, das quais 233 (3,74%) apresentavam a sepse como causa básica antes de serem investigadas e apenas 35 (0,56%) mantiveram-na após a investigação. O preenchimento das declarações com a sepse enquanto causa básica pelos médicos apresentou sensibilidade de 0,9% (IC95%: 0,6 a 1,3) e especificidade de 92,0% (IC95%: 90,9 a 93,1). Conclusão: A baixa acurácia das declarações demonstra a não fidedignidade da causa básica de óbito por sepse, sobretudo, do preenchimento das declarações dos óbitos ocorridos no Distrito Federal em 2018

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

The economic cost of congenital CMV in the UK

Objective: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital disability. It can disrupt neurodevelopment, causing lifelong impairments including sensorineural hearing loss and developmental delay. This study aimed, for the first time, to estimate the annual economic burden of managing cCMV and its sequelae in the UK.Design: The study collated available secondary data to develop a static cost model.Setting: The model aimed to estimate costs of cCMV in the UK for the year 2016.Patients: Individuals of all ages with cCMV.Main outcome measures: Direct (incurred by the public sector) and indirect (incurred personally or by society) costs associated with management of cCMV and its sequelae.Results: The model estimated that the total cost of cCMV to the UK in 2016 was £732�million (lower and upper estimates were between £495 and £942�million). Approximately 40% of the costs were directly incurred by the public sector, with the remaining 60% being indirect costs, including lost productivity. Long-term impairments caused by the virus had a higher financial burden than the acute management of cCMV.Conclusions: The cost of cCMV is substantial, predominantly stemming from long-term impairments. Costs should be compared against investment in educational strategies and vaccine development programmes that aim to prevent virus transmission, as well as the value of introducing universal screening for cCMV to both increase detection of children who would benefit from treatment, and to build a more robust evidence base for future research