Vía aérea difícil en pediatría: signos predictores. Artículo de revisión. Difficult airway in pediatrics. Predicting signs

El manejo de la Vía Aérea es la A del ABC de la medicina moderna y representa un reto para el anestesiólogo experto, y aún más para el que se encuentra en entrenamiento. Una intubación difícil no anticipada es una emergencia médica, si no es tratada con rapidez y de forma apropiada, puede condicionar problemas serios y hasta la muerte del paciente. En el presente artículo se hace una revisión del diagnóstico precoz de esta entidad, mediante signos predictores, teniendo en cuenta algunas de las características principales de la vía aérea del niño que la diferencian del adulto. Palabras clave: predictores, vía aérea, intubación endotraqueal ABSTRACT The management of the airway is the A in the ABC of current medicine, and represents a challenge for an expert in anestesiology, and much more for those in the training process. An anticipated difficult intubation is a medical emergency which must be treated rapidly and properly because it can result in serious problems and lead to death. In this article a review of the early diagnosis of this entity through predicting signs , considering some main features at the child airway which are different from the adult's was carried out. Key words: PREDICTING SIGNS, AIRWAY, ENDOTRACHEAL INTUBATION

Vía aérea difícil en pediatría: signos predictores. Artículo de revisión. Difficult airway in pediatrics. Predicting signs

El manejo de la Vía Aérea es la A del ABC de la medicina moderna y representa un reto para el anestesiólogo experto, y aún más para el que se encuentra en entrenamiento. Una intubación difícil no anticipada es una emergencia médica, si no es tratada con rapidez y de forma apropiada, puede condicionar problemas serios y hasta la muerte del paciente. En el presente artículo se hace una revisión del diagnóstico precoz de esta entidad, mediante signos predictores, teniendo en cuenta algunas de las características principales de la vía aérea del niño que la diferencian del adulto. Palabras clave: predictores, vía aérea, intubación endotraqueal ABSTRACT The management of the airway is the A in the ABC of current medicine, and represents a challenge for an expert in anestesiology, and much more for those in the training process. An anticipated difficult intubation is a medical emergency which must be treated rapidly and properly because it can result in serious problems and lead to death. In this article a review of the early diagnosis of this entity through predicting signs , considering some main features at the child airway which are different from the adult's was carried out. Key words: PREDICTING SIGNS, AIRWAY, ENDOTRACHEAL INTUBATION

Ventilación de alta frecuencia en la cirugía laríngea en pediatría / High frequency ventilation in laringeal surgery in Pediatrics

La laringoscopía directa bajo anestesia general en Pediatría, representa un desafío para anestesiólogos y otorrinolaringólogos, al tener que compartir el reducido espacio de la vía aérea. Se estudiaron 100 pacientes de 5 a 16 años de edad para intervenciones laríngeas con anestesia general, en el Hospital Pediátrico Provincial Docente "Pepe Portilla", de la ciudad de Pinar del Río, Cuba. Se dividieron en 2 grupos de 50 pacientes, el primero con Ventilación a alta frecuencia (VAF), de 2 Hz (FR = 120 respiraciones/minuto) acoplado al Servo Ventilador 900D, y el segundo se ventiló por el método de Sander (modificado por Rivas). La VAF resultó ser un método sencillo y seguro, al poder determinar el volumen y la frecuencia respiratoria correspondiente a cada paciente, a la vez que facilitó el trabajo del cirujano. Las complicaciones fueron mínimas, comprobándose ventajas derivadas del bajo volumen utilizado, consiguiendo un intercambio efectivo de CO2 y O2 con menores presiones de pico, mínimas variaciones en las presiones y en los volúmenes de ventilación y por consiguiente, mínimo impacto sobre la función cardiovascular. Palabras Clave: Laringoscopia, anestesia general, pediatría. ABSTRACT Direct laryngoscopy on general anesthesia in Pediatrics represents a challenge for anesthesiologists and otorrhinolaryngologists, because they have to share the small space of the airways. A number of 100 patients with 5 to 6 years of age were studied for latyngeal interventions with general anesthesia, at Pepe Portilla Provincial Children's Hospital in Pinar del Río, Cuba. Patients were divided into two groups of 50, the first group with high-frequency ventilation (VAF), of 2 Hz (FR = 120 breaths/minute) with Servo Ventilator 900 D, and the second group was ventilated by Sander's method (modified by Rivas). VAP turned out a simple and safe method, by determining volume and the respiratory rate corresponding to each patient, which in turn made it easier for the surgeon. The complications were minimal, showing advantages derived from the low volume used, achieving an effective exchange of CO2 and O2 with lower peak pressures, minimal variations in pressures and volumes of ventilation and, consequently, minimal impact on the cardiovascular performance. Key words: Laringoscopy, general anesthesia, pediatrics

Serinol-Based Benzoic Acid Esters as New Scaffolds for the Development of Adenovirus Infection Inhibitors: Design, Synthesis, and In Vitro Biological Evaluation

Over the years, human adenovirus (HAdV) has progressively been recognized as a significant viral pathogen. Traditionally associated with self-limited respiratory, gastrointestinal, and conjunctival infections, mainly in immunocompromised patients, HAdV is currently considered to be a pathogen presenting significant morbidity and mortality in both immunosuppressed and otherwise healthy individuals. Currently available therapeutic options are limited because of their lack of effectivity and related side effects. In this context, there is an urgent need to develop effective anti-HAdV drugs with suitable therapeutic indexes. In this work, we identified new serinol-derived benzoic acid esters as novel scaffolds for the inhibition of HAdV infections. A set of 38 compounds were designed and synthesized, and their antiviral activity and cytotoxicity were evaluated. Four compounds (13, 14, 27, and 32) inhibited HAdV infection at low micromolar concentrations (2.82–5.35 μM). Their half maximal inhibitory concentration (IC50) values were lower compared to that of cidofovir, the current drug of choice. All compounds significantly reduced the HAdV DNA replication process, while they did not block any step of the viral entry. Our results showed that compounds 13, 14, and 32 seem to be targeting the expression of the E1A early gene. Moreover, all four derivatives demonstrated a significant inhibition of human cytomegalovirus (HCMV) DNA replication. This new scaffold may represent a potential tool useful for the development of effective anti-HAdV drugs.This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos-Proyectos I+D+i (PID2019-104767RB-I00), Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Retos-Proyectos I + D + i (CTQ2016-78580-C2-2-R) and by Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía. M.V.-H. also thanks Ministerio de Economı́a y Competitividad, Plan Estatal 2013-2016 Excelencia I+D+i (CTQ2016-78703-P)

D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data

Importance: Whether and under which conditions D-cycloserine (DCS) augments the effects of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders is unclear. Objective: To clarify whether DCS is superior to placebo in augmenting the effects of cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders and to evaluate whether antidepressants interact with DCS and the effect of potential moderating variables. Data Sources: PubMed, EMBASE, and PsycINFO were searched from inception to February 10, 2016. Reference lists of previous reviews and meta-analyses and reports of randomized clinical trials were also checked. Study Selection: Studies were eligible for inclusion if they were (1) double-blind randomized clinical trials of DCS as an augmentation strategy for exposure-based cognitive behavior therapy and (2) conducted in humans diagnosed as having specific phobia, social anxiety disorder, panic disorder with or without agoraphobia, obsessive-compulsive disorder, or posttraumatic stress disorder. Data Extraction and Synthesis: Raw data were obtained from the authors and quality controlled. Data were ranked to ensure a consistent metric across studies (score range, 0-100). We used a 3-level multilevel model nesting repeated measures of outcomes within participants, who were nested within studies. Results: Individual participant data were obtained for 21 of 22 eligible trials, representing 1047 of 1073 eligible participants. When controlling for antidepressant use, participants receiving DCS showed greater improvement from pretreatment to posttreatment (mean difference, -3.62; 95% CI, -0.81 to -6.43; P = .01; d = -0.25) but not from pretreatment to midtreatment (mean difference, -1.66; 95% CI, -4.92 to 1.60; P = .32; d = -0.14) or from pretreatment to follow-up (mean difference, -2.98, 95% CI, -5.99 to 0.03; P = .05; d = -0.19). Additional analyses showed that participants assigned to DCS were associated with lower symptom severity than those assigned to placebo at posttreatment and at follow-up. Antidepressants did not moderate the effects of DCS. None of the prespecified patient-level or study-level moderators was associated with outcomes. Conclusions and Relevance: D-cycloserine is associated with a small augmentation effect on exposure-based therapy. This effect is not moderated by the concurrent use of antidepressants. Further research is needed to identify patient and/or therapy characteristics associated with DCS response.2018-05-0

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic.

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world

Vía aérea difícil en pediatría: signos predictores. Artículo de revisión Difficult airway in pediatrics. Predicting signs

El manejo de la Vía Aérea es la A del ABC de la medicina moderna y representa un reto para el anestesiólogo experto, y aún más para el que se encuentra en entrenamiento. Una intubación difícil no anticipada es una emergencia médica, si no es tratada con rapidez y de forma apropiada, puede condicionar problemas serios y hasta la muerte del paciente. En el presente artículo se hace una revisión del diagnóstico precoz de esta entidad, mediante signos predictores, teniendo en cuenta algunas de las características principales de la vía aérea del niño que la diferencian del adulto.<br>The management of the airway is the A in the ABC of current medicine, and represents a challenge for an expert in anestesiology, and much more for those in the training process. An anticipated difficult intubation is a medical emergency which must be treated rapidly and properly because it can result in serious problems and lead to death. In this article a review of the early diagnosis of this entity through predicting signs , considering some main features at the child airway which are different from the adult's was carried out