Dynamics of disease characteristics and clinical management of critically ill COVID-19 patients over the time course of the pandemic: an analysis of the prospective, international, multicentre RISC-19-ICU registry.

BACKGROUND It remains elusive how the characteristics, the course of disease, the clinical management and the outcomes of critically ill COVID-19 patients admitted to intensive care units (ICU) worldwide have changed over the course of the pandemic. METHODS Prospective, observational registry constituted by 90 ICUs across 22 countries worldwide including patients with a laboratory-confirmed, critical presentation of COVID-19 requiring advanced organ support. Hierarchical, generalized linear mixed-effect models accounting for hospital and country variability were employed to analyse the continuous evolution of the studied variables over the pandemic. RESULTS Four thousand forty-one patients were included from March 2020 to September 2021. Over this period, the age of the admitted patients (62 [95% CI 60-63] years vs 64 [62-66] years, p < 0.001) and the severity of organ dysfunction at ICU admission decreased (Sequential Organ Failure Assessment 8.2 [7.6-9.0] vs 5.8 [5.3-6.4], p < 0.001) and increased, while more female patients (26 [23-29]% vs 41 [35-48]%, p < 0.001) were admitted. The time span between symptom onset and hospitalization as well as ICU admission became longer later in the pandemic (6.7 [6.2-7.2| days vs 9.7 [8.9-10.5] days, p < 0.001). The PaO2/FiO2 at admission was lower (132 [123-141] mmHg vs 101 [91-113] mmHg, p < 0.001) but showed faster improvements over the initial 5 days of ICU stay in late 2021 compared to early 2020 (34 [20-48] mmHg vs 70 [41-100] mmHg, p = 0.05). The number of patients treated with steroids and tocilizumab increased, while the use of therapeutic anticoagulation presented an inverse U-shaped behaviour over the course of the pandemic. The proportion of patients treated with high-flow oxygen (5 [4-7]% vs 20 [14-29], p < 0.001) and non-invasive mechanical ventilation (14 [11-18]% vs 24 [17-33]%, p < 0.001) throughout the pandemic increased concomitant to a decrease in invasive mechanical ventilation (82 [76-86]% vs 74 [64-82]%, p < 0.001). The ICU mortality (23 [19-26]% vs 17 [12-25]%, p < 0.001) and length of stay (14 [13-16] days vs 11 [10-13] days, p < 0.001) decreased over 19 months of the pandemic. CONCLUSION Characteristics and disease course of critically ill COVID-19 patients have continuously evolved, concomitant to the clinical management, throughout the pandemic leading to a younger, less severely ill ICU population with distinctly different clinical, pulmonary and inflammatory presentations than at the onset of the pandemic

Tipificación del fenotipo inflamatorio en el asma bronquial en niños de 7 a 14 años, mediante recuento celular y determinación de citoquinas en esputo inducido

Introducción: La inducción de esputo es una técnica escasamente invasora para el estudio y la monitorización de la inflamación de la vía aérea. Objetivos: El objetivo principal del estudio fue comparar el perfil celular y los niveles de citoquinas Th1 y Th2 en esputo inducido entre niños asmáticos atópicos, asmáticos no atópicos y sanos. Métodos: La inducción de esputo fue realizada mediante inhalación de suero salino hipertónico a concentraciones crecientes (3%, 4% y 5%). Se determinó la fracción exhalada de óxido nítrico en los pacientes asmáticos y se midió la FEV1 al inicio y después de cada período de inhalación para garantizar la seguridad de los niños. El procesado del esputo se hizo siguiendo el método de Pizzichini y cols. Se separó el esputo de la saliva y se añadió un volumen de solución de ditiotreitol igual a 4 veces el peso del esputo. Se agitó la mezcla y después de colocarla en banco mecedor durante 10 minutos se añadieron 4 volúmenes de PBS de Dulbecco. La suspensión resultante se filtró a través de una gasa de nylon de 48 micras, centrifugándose a continuación durante 10 minutos a 2.500 rpm para obtener un pellet (sedimento) celular donde se determinaron el recuento celular total y la viabilidad celular y un sobrenadante que se guardó a -80ºC para la determinación de citoquinas. Se consideró una buena muestra si la viabilidad celular era > 60% y la contaminación por células escamosas < 20%. Mediante citocentrífuga se obtuvieron las preparaciones y tras tinción de May-Grünwald-Giemsa se realizó el recuento celular diferencial con microscopio óptico. Los niveles de IFN-gamma, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1beta, TNF-alfa, e IL-12p70 en el sobrenadante se determinaron mediante citometría de flujo (Bender Medsystem, USA). El análisis estadístico se realizó con el programa SPSS15.0. Se aplicaron los siguientes tests paramétricos o no paramétricos según los grupos seguían o no una distribución normal (prueba de normalidad de Kolmogorow-Smirnov), y según fuera apropiado: t de Student para datos no apareados, análisis de la varianza de una vía, test no paramétricos de la U de Mann-Witney, y de Kruskal-Wallis, Chi-cuadrado, prueba exacta de Fisher y correlación lineal de Pearson. Se consideraron significativos valores de p < 0,05. Los resultados se expresaron como media y desviación estándar (DE) o mediana y rango intercuartílico. Resultados: Se realizó inducción de esputo a 77 niños asmáticos (52 varones) y a 31 sanos (17 varones) de 7 a 15 años. Entre los asmáticos, 51 no recibían tratamiento y 26 recibían corticoides inhalados. Diecisiete pacientes presentaban un asma no atópica y 60 asma atópica. Se obtuvieron 64 muestras en los asmáticos (83,1% de las inducciones) y 24 muestras en los niños sanos (77,4%) de las que 49 y 18 adecuadas respectivamente. La mediana de eosinófilos en esputo inducido de los asmáticos atópicos (1,5%) fue mayor que en los no atópicos (0%) (p=0,02) y que en los niños sanos (0%) (p=0,003). Las citoquinas Th2 (IL-4 e IL-5) y Th1 (IFNgamma, IL-2 e IL-12p70) fueron superiores en los asmáticos atópicos que en los sanos y en los asmáticos no atópicos (p<0,0001). La IL-8 fue mayor en los niños asmáticos (atópicos y no atópicos) que en los controles (p<0,0001). La IL-10 fue mayor en los controles que en los asmáticos atópicos (p=0,03). No existieron diferencias en el resto de citoquinas (IL-6, IL-1beta y TNF-alfa). Conclusiones: El perfil inflamatorio de los niños asmáticos muestra un aumento en las citoquinas proinflamatorias en el esputo inducido respecto a los niños sanos. Existen diferencias en el perfil de citoquinas en esputo inducido entre los niños asmáticos atópicos y no atópicos.Introduction: Sputum induction is a semi-invasive technique for the study and monitorization of airway inflammation. Objectives: The aim of the present study was to compare the cellular profile and the Th1 and Th2 cytokine levels in induced sputum between atopic asthmatic, non atopic asthmatic and healthy children. Methods: Sputum induction was performed by inhalation of a hypertonic saline solution at increasing concentrations (3%, 4% and 5%). Fractional exhaled nitric oxide was determinate in asthmatic patients and FEV1 was measured at the start and after each period of inhalation to ensure children’s safety. Sputum examination was performed as described by Pizzichini et al. Sputum was separated from contaminating saliva and a weighed aliquot was dispersed with four volumes of freshly prepared dithiothreitol solution. The mixture was vortexed, and after being rocked for 10 minutes, 4 volumes of Dulbecco’s PBS was added. The suspension was then filtered through 48-µm nylon gauze and centrifuged at 2500 rpm for 10 minutes. This resulted in the formation of a cell pellet and supernatant solution. The supernatant was stored at -80º C for analysis of cytokines. Total cell count and cell viability was determined in the cell pellet. We considered good sample if there was cell viability ≥ 60% and contamination by squamous cells < 20%. Cytospin cell preparations were made using a cytocentrifuge and slides were stained with May-Grünwald-Giemsa to determine the differential cell count using optic microscopy. In sputum sample supernatants IFN-γ, IL-2, IL-10, IL-8, IL-6, IL-4, IL-5, IL-1β, TNF-α, and IL-12p70 levels were determined by flow cytometry (Bender Medsystem, USA). Statistical analyse was performed with SPSS® 15.0 program. Parametric and non-parametric tests were applied according to normal distribution (Kolmogorov-Smirnov test): Student’s t-test for independent samples, ANOVA, Mann-Whitney U test and Kruskal-Wallis as non-parametric tests, Chi-square test and Pearson’s correlation. Values of p < 0.05 were considered significant. Results are expressed as mean and standard deviation (SD) or median and interquartile range. Results: Sputum induction was performed in 77 asthmatic children (52 boys) and in 31 healthy children (17 boys) from 7 to 15 years old. Fifty one of asthmatic children were with no treatment and 26 were receiving inhaled corticosteroids. Seventeen patients had non atopic asthma and 60 had atopic asthma. We obtained 64 samples in patients (83.1% of inductions) and 24 samples in healthy children (77.4%). We considered 49 and 18 good samples respectively. Median eosinophil count in atopic asthma (1.5%) was higher than in nonatopic asthma (0%) (p=0.02) or healthy children (0%) (p=0.003). Th2 cytokines (IL-4 and IL-5) and Th1 cytokines (IFNγ, IL-2 and IL-12p70) were higher in atopic asthmatic children than in healthy and non atopic asthmatic children (p<0,0001). IL-8 was higher in asthmatic children (atopic and non atopic) than controls (p<0,0001). IL-10 was higher in controls than atopic asthmatic children (p=0,03). There were no differences in the other cytokines (IL-6, IL-1β and TNF-α). Conclusions: The inflammatory profil of asthmatic children shows an increase in proinflammatory cytokines in induced sputum respect to healthy children. There are differences in cytokine profile of induced sputum in atopic and non atopic asthmatic children

[Continuum of risky eating behaviors in Mexican adolescents]

OBJECTIVE: Determine the relationship between the variables of self-esteem (SE), body dissatisfaction (BD), and body mass index (BMI) in a continuum of risky eating behaviors (REB) that ranges from normal behavior to the risk of eating disorders (ED), thus facilitating early detection of adolescents with ED symptomatology and the degree to which such variables have an influence. METHODS: A total of 1 982 young women aged 15-19 were selected through stratified random sampling. Self-esteem (Pope, McHale, and Craighead scale), body dissatisfaction (Stunkard's Figure Rating Scale), and body mass index were measured. A brief REB questionnaire was administered. Three categories of REB were defined: no risk, moderate risk, and high risk. A multiple regression analysis was performed. RESULTS: A direct relationship was found between risk of REB and BD, with significant differences between the groups (P < 0.001): no risk (83.6% of sample), 54.1% had BD; moderate risk (11.9% of sample), 84.8% had BD; and high risk (4.5% of sample), 89.9% had BD. There were significant differences in SE and BMI only between the group with no risk and each of the risk groups. Self-esteem played a role in predicting REB in all the regression models evaluated, whereas BMI did not. CONCLUSIONS: It is essential to identify adolescents at moderate risk of REB who have prodromic features of ED such as low SE and BD. When these features occur simultaneously, they can mediate a negative effect of BMI on REB

Continuo de conductas alimentarias de riesgo en adolescentes de México Continuum of risky eating behaviors in Mexican adolescents

OBJETIVO: Determinar las relaciones existentes entre las variables autoestima (AU), insatisfacción corporal (IC) e índice de masa corporal (IMC) en un continuo de conductas alimentarias de riesgo (CAR) que abarque desde la normalidad hasta el riesgo de trastornos de conducta alimentaria (TCA), facilitando así la detección temprana de adolescentes con manifestaciones de TCA y el grado en que influyen dichas variables. MÉTODOS: Se seleccionaron 1 982 mujeres de 15 a 19 años de edad, de acuerdo con un muestreo aleatorio estratificado. Se midió la AU (escala de Pope, McHale y Craighead), la IC ("Escala análoga de figuras corporales" de Stunkard) y el IMC. Se administró un cuestionario breve de CAR. Se definieron tres categorías de CAR: sin riesgo, riesgo moderado y riesgo alto. Se realizó la prueba de regresión multinomial. RESULTADOS: Se encontró una relación directa entre el riesgo de CAR y la IC, con diferencias significativas entre grupos (P < 0,001): sin riesgo (83,6% de la muestra) 54,1% presentaron IC; con riesgo moderado (11,9% de la muestra) 84,8% presentaron IC, y de riesgo alto (4,5% de la muestra) 89,9% presentaron IC. En AU e IMC solo hubo diferencias significativas entre el grupo sin riesgo y cada uno de los grupos de riesgo. La AU participó en la predicción de CAR en todos los modelos de regresión evaluados, mientras que el IMC no lo hizo. CONCLUSIONES: Es perentorio identificar adolescentes en riesgo moderado de CAR que revelen características prodrómicas de TCA, como baja AU e IC, las cuales, cuando se presentan de forma conjunta, pueden mediar un efecto negativo del IMC sobre las CAR<br>OBJECTIVE: Determine the relationship between the variables of self-esteem (SE), body dissatisfaction (BD), and body mass index (BMI) in a continuum of risky eating behaviors (REB) that ranges from normal behavior to the risk of eating disorders (ED), thus facilitating early detection of adolescents with ED symptomatology and the degree to which such variables have an influence. METHODS: A total of 1 982 young women aged 15-19 were selected through stratified random sampling. Self-esteem (Pope, McHale, and Craighead scale), body dissatisfaction (Stunkard's Figure Rating Scale), and body mass index were measured. A brief REB questionnaire was administered. Three categories of REB were defined: no risk, moderate risk, and high risk. A multiple regression analysis was performed. RESULTS: A direct relationship was found between risk of REB and BD, with significant differences between the groups (P < 0.001): no risk (83.6% of sample), 54.1% had BD; moderate risk (11.9% of sample), 84.8% had BD; and high risk (4.5% of sample), 89.9% had BD. There were significant differences in SE and BMI only between the group with no risk and each of the risk groups. Self-esteem played a role in predicting REB in all the regression models evaluated, whereas BMI did not. CONCLUSIONS: It is essential to identify adolescents at moderate risk of REB who have prodromic features of ED such as low SE and BD. When these features occur simultaneously, they can mediate a negative effect of BMI on RE

[Continuum of risky eating behaviors in Mexican adolescents]

OBJECTIVE: Determine the relationship between the variables of self-esteem (SE), body dissatisfaction (BD), and body mass index (BMI) in a continuum of risky eating behaviors (REB) that ranges from normal behavior to the risk of eating disorders (ED), thus facilitating early detection of adolescents with ED symptomatology and the degree to which such variables have an influence. METHODS: A total of 1 982 young women aged 15-19 were selected through stratified random sampling. Self-esteem (Pope, McHale, and Craighead scale), body dissatisfaction (Stunkard's Figure Rating Scale), and body mass index were measured. A brief REB questionnaire was administered. Three categories of REB were defined: no risk, moderate risk, and high risk. A multiple regression analysis was performed. RESULTS: A direct relationship was found between risk of REB and BD, with significant differences between the groups (P < 0.001): no risk (83.6% of sample), 54.1% had BD; moderate risk (11.9% of sample), 84.8% had BD; and high risk (4.5% of sample), 89.9% had BD. There were significant differences in SE and BMI only between the group with no risk and each of the risk groups. Self-esteem played a role in predicting REB in all the regression models evaluated, whereas BMI did not. CONCLUSIONS: It is essential to identify adolescents at moderate risk of REB who have prodromic features of ED such as low SE and BD. When these features occur simultaneously, they can mediate a negative effect of BMI on REB