La experiencia de una unidad de cuidados intensivos pediátricos en el manejo de pacientes adultos con enfermedad COVID-19 / A paediatric intensive care unit's experience in managing adult patients with COVID-19 disease

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An algorithm combining procalcitonin and lung ultrasound improves the diagnosis of bacterial pneumonia in critically ill children: The PROLUSP study, a randomized clinical trial.

BACKGROUND: Lung ultrasound (LUS) and procalcitonin (PCT) are independently used to improve accuracy when diagnosing lung infections. The aim of the study was to evaluate the accuracy of a new algorithm combining LUS and PCT for the diagnosis of bacterial pneumonia. METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children <18 years old with suspected pneumonia admitted to pediatric intensive care unit were included, and randomized into experimental group (EG) or control group (CG) if LUS or chest X-Ray (CXR) were done as the first pulmonary image, respectively. PCT was determined. In patients with bacterial pneumonia, sensitivity, specificity, and predictive values of LUS, CXR, and of both combined with PCT were analyzed and compared. Concordance between the final diagnosis and the diagnosis concluded through the imaging test was assessed. RESULTS: A total of 194 children, with a median age of 134 (interquartile range [IQR]: 39-554) days, were enrolled, 96 randomized into the EG and 98 into the CG. Bacterial pneumonia was diagnosed in 97 patients. Sensitivity and specificity for bacterial pneumonia diagnosis were 78% (95% confidence interval [CI]: 70-85) and 98% (95% CI: 93-99) for LUS, 85% (95% CI: 78-90) and 53% (95% CI: 43-62) for CXR, 90% (95% CI: 83-94) and 85% (95% CI: 76-91) when combining LUS and PCT, and 95% (95% CI: 90-98) and 41% (95% CI: 31-52) when combining CXR and PCT. The positive predictive value for LUS and PCT was 88% (95% C:I 79%-93%) versus 68% (95% CI: 60-75) for CXR and PCT. The concordance between the final diagnosis and LUS had a kappa value of 0.69 (95% CI: 0.62-0.75) versus 0.34 (95% CI: 0.21-0.45) for CXR, (p < 0.001). CONCLUSIONS: The combination of LUS and PCT presented a better accuracy for bacterial pneumonia diagnosis than combining CXR and PCT. Therefore, its implementation could be a reliable tool for pneumonia diagnosis in critically ill children.

Cerebrospinal fluid neopterin as a biomarker of neuroinflammatory diseases.

The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case-control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.

Cardiovascular adaptation to extrauterine life after intrauterine growth restriction.

Introduction The adaptive changes of the foetal heart in intrauterine growth restriction can persist postnatally. Data regarding its consequences for early circulatory adaptation to extrauterine life are scarce. The aim of this study was to assess cardiac morphometry and function in newborns with late-onset intrauterine growth restriction to test the hypothesis that intrauterine growth restriction causes cardiac shape and functional changes at birth. METHODS: A comprehensive echocardiographic study was performed in 25 neonates with intrauterine growth restriction and 25 adequate-for-gestational-age neonates. RESULTS: Compared with controls, neonates with intrauterine growth restriction had more globular ventricles, lower longitudinal tricuspid annular motion, and higher left stroke volume without differences in the heart rate. Neonates with intrauterine growth restriction also showed subclinical signs of diastolic dysfunction in the tissue Doppler imaging with lower values of early (e') diastolic annular peak velocities in the septal annulus. Finally, the Tei index in the tricuspid annulus was higher in the intrauterine growth restriction group. CONCLUSION: Neonates with history of intrauterine growth restriction showed cardiac remodelling and signs of systolic and diastolic dysfunction. Overall, there was a significant tendency to worse cardiac function results in the right heart. The adaptation to extrauterine life occurred with more globular hearts, higher stroke volumes but a similar heart rate compared to adequate-for-gestational-age neonates.

Cuantificación del estrés: información incompleta más un exceso de triunfalismo. Réplica / Quantification of stress: incomplete information plus excessive triumphalism. Reply

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Proyecto ES3: intentando la cuantificación y medida del nivel de estrés / Project ES3: attempting to quantify and measure the level of stress

Introducción. La Organización Mundial de la Salud ha calificado al estrés de ‘epidemia mundial’, debido a su cada vez mayor incidencia en la salud. El trabajo que se presenta en este artículo representa un intento de cuantificar objetivamente el nivel de estrés. Objetivo. La metodología desarrollada tiene como objetivo medir cuán lejos o cuán cerca se encuentra un sujeto de una situación considerada médica y socialmente como ‘normal’. Sujetos y métodos. Se ha realizado un estudio bibliográfico de la fisiopatología del estrés y sus métodos de estudio, en experimentación animal y en humanos. Se han puesto en marcha nueve estudios prospectivos observacionales con distintas tipologías de sujetos y estresores que cubren las diferentes tipologías de estrés. Resultados. Como resultado del estudio bibliográfico, se han identificado las distintas tipologías de estrés, los indicadores que describen resultados significativos, los tests psicométricos y los ‘agentes estresantes’ bien documentados. Este material ha permitido diseñar la metodología general y el detalle de los nueve ensayos clínicos. Los resultados preliminares obtenidos en algunos de los estudios han servido para validar los indicadores, así como la eficacia de las técnicas utilizadas experimentalmente para disminuir el estrés o para producirlo. Conclusiones. Los resultados preliminares obtenidos en los ensayos experimentales muestran que se está en el camino correcto hacia la definición y validación de marcadores multivariable para la cuantificación de los niveles de estrés, y sugieren que la metodología puede ser aplicada de forma similar al estudio de trastornos mentales (AU)

Introduction. The WHO has qualified stress as a ‘world epidemic’ due to its increasingly greater incidence on health. The work described in this paper represents an attempt to objectively quantify the level of stress. Aim. The aim of the method developed here is to measure how close or how far a subject is from a situation that can be considered ‘normal’ in medical and social terms. Subjects and methods. The literature on the pathophysiology of stress and its methods of study in experiments on both animals and humans was reviewed. Nine prospective observational studies were undertaken with different types of subjects and stressors covering the different types of stress. Results. The results of the literature review made it possible to identify the different types of stress, the indicators that yield significant results, the psychometric tests and the well-documented ‘stressors’. This material was then used to design the general method and the details of the nine clinical trials. The preliminary results obtained in some of the studies were used to validate the indicators as well as the efficacy of the techniques used experimentally to diminish stress or to produce it. Conclusions. The early results obtained in the experimental trials show that we are on the right path towards defining and validating multivariable markers for quantifying levels of stress and also suggest that the method can be applied in a similar way to the study of mental disorders (AU)

Project ES3: attempting to quantify and measure the level of stress.

INTRODUCTION: The WHO has qualified stress as a 'world epidemic' due to its increasingly greater incidence on health. The work described in this paper represents an attempt to objectively quantify the level of stress. AIM: The aim of the method developed here is to measure how close or how far a subject is from a situation that can be considered 'normal' in medical and social terms. SUBJECTS AND METHODS: The literature on the pathophysiology of stress and its methods of study in experiments on both animals and humans was reviewed. Nine prospective observational studies were undertaken with different types of subjects and stressors covering the different types of stress. RESULTS: The results of the literature review made it possible to identify the different types of stress, the indicators that yield significant results, the psychometric tests and the well-documented 'stressors'. This material was then used to design the general method and the details of the nine clinical trials. The preliminary results obtained in some of the studies were used to validate the indicators as well as the efficacy of the techniques used experimentally to diminish stress or to produce it. CONCLUSIONS: The early results obtained in the experimental trials show that we are on the right path towards defining and validating multivariable markers for quantifying levels of stress and also suggest that the method can be applied in a similar way to the study of mental disorders.

TITLE: Proyecto ES3: intentando la cuantificacion y medida del nivel de estres.Introduccion. La Organizacion Mundial de la Salud ha calificado al estres de 'epidemia mundial', debido a su cada vez mayor incidencia en la salud. El trabajo que se presenta en este articulo representa un intento de cuantificar objetivamente el nivel de estres. Objetivo. La metodologia desarrollada tiene como objetivo medir cuan lejos o cuan cerca se encuentra un sujeto de una situacion considerada medica y socialmente como 'normal'. Sujetos y metodos. Se ha realizado un estudio bibliografico de la fisiopatologia del estres y sus metodos de estudio, en experimentacion animal y en humanos. Se han puesto en marcha nueve estudios prospectivos observacionales con distintas tipologias de sujetos y estresores que cubren las diferentes tipologias de estres. Resultados. Como resultado del estudio bibliografico, se han identificado las distintas tipologias de estres, los indicadores que describen resultados significativos, los tests psicometricos y los 'agentes estresantes' bien documentados. Este material ha permitido diseñar la metodologia general y el detalle de los nueve ensayos clinicos. Los resultados preliminares obtenidos en algunos de los estudios han servido para validar los indicadores, asi como la eficacia de las tecnicas utilizadas experimentalmente para disminuir el estres o para producirlo. Conclusiones. Los resultados preliminares obtenidos en los ensayos experimentales muestran que se esta en el camino correcto hacia la definicion y validacion de marcadores multivariable para la cuantificacion de los niveles de estres, y sugieren que la metodologia puede ser aplicada de forma similar al estudio de trastornos mentales.

Adrenomedullin is a useful biomarker for the prognosis of critically ill septic children.

AIM: To measure midregional pro-adrenomedullin (MR-pro-ADM) in critically ill septic patients to determine its prognostic usefulness as compared with other used biomarkers in pediatric intensive care units, C-reactive protein (CRP) and procalcitonin (PCT). MATERIALS & METHODS: Prospective observational study conducted on 95 patients. RESULTS: Mean levels of MR-pro-ADM were significantly higher when patients needed mechanical ventilation (3.2 ± 4.3 vs 1.6 ± 2.4) and inotropes (4.4 ± 5.2 vs 1.3 ± 1.2). Receiver operating characteristic curves of mortality were higher for MR-pro-ADM (cut-off value of 2.2). This marker showed higher positive predictive prognostic value than PCT and CRP (31 vs 21.6% and 15.8%, respectively). CONCLUSION: MR-pro-ADM levels are good indicators of disease severity and show better reliability than PCT and CRP for predicting in-hospital mortality.

Lipophilic antioxidants in patients with phenylketonuria.

BACKGROUND: Low serum ubiquinone-10 concentrations have been described in phenylketonuric patients fed natural-protein-restricted diets. Such low concentrations may be related to increased free radical damage. OBJECTIVE: We evaluated the relation between low serum ubiquinone-10 concentrations and other lipophilic antioxidants (tocopherol and retinol), selenium, glutathione peroxidase activity, and malondialdehyde concentrations as a marker of lipid peroxidation. DESIGN: This was a cross-sectional study of 58 patients with phenylketonuria (aged 2-36 y; median: 13 y) under dietary treatment, 58 age-matched control subjects, and 30 children with moderate hyperphenylalaninemia fed unrestricted diets (aged 3-17 y; median: 7.5 y). Serum ubiquinone-10 concentrations were analyzed by HPLC with electrochemical detection. Serum retinol, serum tocopherol, and plasma malondialdehyde were analyzed by HPLC with ultraviolet detection. RESULTS: A significant positive correlation was observed between ubiquinone-10 and tocopherol (r = 0.510, P < 0.001) in the patients with phenylketonuria. After the patients were stratified into 2 groups according to ubiquinone-10 values, significantly lower concentrations of tocopherol were observed in group 1 (low ubiquinone values) than in group 2 (normal ubiquinone values), the hyperphenylalaninemic children, and the control group. Plasma malondialdehyde concentrations were significantly higher in group 1 than in the other groups. No significant differences between groups 1 and 2 were observed in daily intakes of selenium, ascorbate, tocopherol, or retinol. CONCLUSIONS: Plasma lipid peroxidation seems to be increased in phenylketonuria. Low concentrations of ubiquinone-10 could be associated with either excessive tocopherol consumption or high malondialdehyde concentrations in patients with phenylketonuria.

Ubiquinone-10 content in lymphocytes of phenylketonuric patients.

OBJECTIVES: To investigate the ubiquinone-10 content in lymphocytes from phenylketonuric patients. DESIGN AND METHODS: We compared 23 patients with 25 age-matched controls. Ubiquinone-10 was analyzed by HPLC with electrochemical detection. RESULTS: Ubiquinone-10 concentrations were significantly lower in patients (77-270 nmol/g of protein) compared with controls (190-550) (p < 0.001). Significantly negative correlation was observed between ubiquinone-10 and phenylalanine (r = -0.441; p < 0.05). CONCLUSIONS: Ubiquinone-10 concentrations are decreased in lymphocytes from phenylketonuric patients. This deficiency is associated with high plasma phenylalanine concentrations.