Nuevas recomendaciones sobre el uso de corticoides en el paciente crítico

La utilización de corticoides en el paciente crítico es una práctica clínica habitual, aunque no siempre respaldada por la evidencia científica. Los datos aportados por estas nuevas guías intentan responder a algunas de las dudas que se nos plantean diariamente en el ejercicio de nuestra actividad. ABSTRACT  The use of corticosteroids in critically ill patients is a common clinical practice, although not always supported by scientific evidence. The recommendations provided by these new guides try to answer some ot the questions tha we have to face daily in the exercise of our activity

Nuevas recomendaciones sobre el uso de corticoides en el paciente crítico

The use of corticosteroids in critically ill patients is a common clinical practice, although not always supported by scientific evidence. The recommendations provided by these new guides try to answer some ot the questions tha we have to face daily in the exercise of our activity.La utilización de corticoides en el paciente crítico es una práctica clínica habitual, aunque no siempre respaldada por la evidencia científica. Los datos aportados por estas nuevas guías intentan responder a algunas de las dudas que se nos plantean diariamente en el ejercicio de nuestra actividad.

Driving pressure y mortalidad en el síndrome de distrés respiratorio agudo

Current guidelines for ventilation in patients with acute respiratory distress syndrome (ARDS) recommend lung-protective ventilation: use of low tidal volumes, appropiate  positive end-expiratory pressure and alveolar recruitment maneuvers. However, recent studies have shown that driving pressure could be the variable that best correlated with survival in patients with ARDS.Las actuales guías de manejo del síndrome de distrés respiratorio agudo (SDRA) recomiendan una ventilación protectora: volumen corriente bajo, presión positiva al final de la espiración (PEEP) adecuada y maniobras de reclutamiento alveolar. Sin embargo, estudios recientes han mostrado que la driving pressure podría ser la variable que mejor se correlaciona con la supervivencia en pacientes con SDRA

Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61‐8048 after chronic intermittent ethanol in mice

Background and Purpose: The kynurenine pathway has been proposed as a target for modulating drug abuse. We previously demonstrated that inhibition of kynurenine 3-monooxygenase (KMO), using Ro 61-8048, reduces ethanol consumption in a binge drinking model. Here, we investigate the effect of the kynurenine pathway modulation in ethanol-dependent mice. Experimental Approach: Adult male and female mice were subjected to a Chronic Intermittent Ethanol (CIE) paradigm. On the last day of CIE, mice were treated with Ro 61-8048, Ro 61-8048 + PNU-120596, a positive allosteric modulator of α7nAChR, and Ro 61-8048 + L-leucine or probenecid, which blocks the influx or efflux of kynurenine from the brain, respectively. Ethanol, water consumption and preference were measured and kynurenine levels in plasma and limbic forebrain were determined. Key Results: Ro 61-8048 decreases consumption and preference for ethanol in both sexes exposed to the CIE model, an effect that was prevented by PNU-120596. The Ro 61-8048-induced decrease in ethanol consumption depends on the influx of kynurenine into the brain. Conclusion and Implications: Inhibition of KMO reduces ethanol consumption and preference in both male and female mice subjected to CIE model by a mechanism involving α7nAChR. Moreover, this centrally-mediated effect depends on the influx of peripheral kynurenine to the brain and can be prolonged by blocking the efflux of kynurenine from the brain. Here, for the first time, we demonstrate that the modulation of the kynurenine pathway is an effective strategy for the treatment of ethanol dependence in both sexe

Longitudinal dynamics of SARS-CoV-2-specific cellular and humoral immunity after natural infection or BNT162b2 vaccination

The timing of the development of specific adaptive immunity after natural SARS-CoV-2 infection, and its relevance in clinical outcome, has not been characterized in depth. Description of the long-term maintenance of both cellular and humoral responses elicited by real-world anti-SARS-CoV-2 vaccination is still scarce. Here we aimed to understand the development of optimal protective responses after SARS-CoV-2 infection and vaccination. We performed an early, longitudinal study of S1-, M- and N-specific IFN-γ and IL-2 T cell immunity and anti-S total and neutralizing antibodies in 88 mild, moderate or severe acute COVID-19 patients. Moreover, SARS-CoV-2-specific adaptive immunity was also analysed in 234 COVID-19 recovered subjects, 28 uninfected BNT162b2-vaccinees and 30 uninfected healthy controls. Upon natural infection, cellular and humoral responses were early and coordinated in mild patients, while weak and inconsistent in severe patients. The S1-specific cellular response measured at hospital arrival was an independent predictive factor against severity. In COVID-19 recovered patients, four to seven months post-infection, cellular immunity was maintained but antibodies and neutralization capacity declined. Finally, a robust Th1-driven immune response was developed in uninfected BNT162b2-vaccinees. Three months post-vaccination, the cellular response was comparable, while the humoral response was consistently stronger, to that measured in COVID-19 recovered patients. Thus, measurement of both humoral and cellular responses provides information on prognosis and protection from infection, which may add value for individual and public health recommendations

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Toledo: problemática e implicaciones urbanas del turismo

Se utiliza Toledo como experiencia piloto para desarrollar una metodología multicriterio orientada a explicar las interdependencias entre turismo y realidad urbana. Se presenta dicha metodología y los aspectos más relevantes en relación con los recursos culturales de] centro histórico, los flujos de visitantes, infraestructuras de acogida, etc. Se concluye con una interpretación general del modelo turístico de Toledo, definido como un destino maduro con débiles infraestructuras de gestión y precaria integración del turismo en la vida de la ciuda