Critical COPD respiratory illness is linked to increased transcriptomic activity of neutrophil proteases genes

BACKGROUND: Gene expression profiling (GEP) in cells obtained from peripheral blood has shown that this is a very useful approach for biomarker discovery and for studying molecular pathogenesis of prevalent diseases. While there is limited literature available on gene expression markers associated with Chronic Obstructive Pulmonary Disease (COPD), the transcriptomic picture associated with critical respiratory illness in this disease is not known at the present moment. FINDINGS: By using Agilent microarray chips, we have profiled gene expression signatures in the whole blood of 28 COPD patients hospitalized with different degrees of respiratory compromise.12 of them needed of admission to the ICU, whilst 16 were admitted to the Respiratory Medicine Service. GeneSpring GX 11.0 software was used for performing statistical comparisons of transcript levels between ICU and non-ICU patients. Ingenuity pathway analysis 8.5 (IPA) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to select, annotate and visualize genes by function and pathway (gene ontology). T-test showed evidence of 1501 genes differentially expressed between ICU and non-ICU patients. IPA and KEGG analysis of the most representative biological functions revealed that ICU patients had increased levels of neutrophil gene transcripts, being [cathepsin G (CTSG)], [elastase, neutrophil expressed (ELANE)], [proteinase 3 (PRTN3)], [myeloperoxidase (MPO)], [cathepsin D (CTSD)], [defensin, alpha 3, neutrophil-specific (DEFA3)], azurocidin 1 (AZU1)], and [bactericidal/permeability-increasing protein (BPI)] the most representative ones. Proteins codified by these genes form part of the azurophilic granules of neutrophils and are involved in both antimicrobial defence and tissue damage. This “neutrophil signature” was paralleled by the necessity of advanced respiratory and vital support, and the presence of bacterial infection. CONCLUSION: Study of transcriptomic signatures in blood suggests an essential role of neutrophil proteases in COPD patients with critical respiratory illness. Measurement and modulation of the expression of these genes could present an option for clinical monitoring and treatment of severe COPD exacerbations

Approaching Personalized Medicine: The Use of Machine Learning to Determine Predictors of Mortality in a Population with SARS-CoV-2 Infection

The COVID-19 pandemic demonstrated the need to develop strategies to control a new viral infection. However, the different characteristics of the health system and population of each country and hospital would require the implementation of self-systems adapted to their characteristics. The objective of this work was to determine predictors that should identify the most severe patients with COVID-19 infection. Given the poor situation of the hospitals in the first wave, the analysis of the data from that period with an accurate and fast technique can be an important contribution. In this regard, machine learning is able to objectively analyze data in hourly sets and is used in many fields. This study included 291 patients admitted to a hospital in Spain during the first three months of the pandemic. After screening seventy-one features with machine learning methods, the variables with the greatest influence on predicting mortality in this population were lymphocyte count, urea, FiO2, potassium, and serum pH. The XGB method achieved the highest accuracy, with a precision of >95%. Our study shows that the machine learning-based system can identify patterns and, thus, create a tool to help hospitals classify patients according to their severity of illness in order to optimize admission

Case Report Posterior Reversible Encephalopathy Syndrome as Presenting Form of Very Early Systemic Sclerosis

Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed "active pattern, " considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon

Posterior Reversible Encephalopathy Syndrome as Presenting Form of Very Early Systemic Sclerosis

Introduction. Posterior Reversible Encephalopathy Syndrome (PRES) is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP) and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc) not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI) showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed “active pattern,” considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon

Prescripción basada en evidencia científica en la atención primaria de salud Scientific evidence-based prescribing in primary health care

Introducción: la medicina basada en evidencia es una respuesta natural a la necesidad de crear un modelo de atención médica que permita la integración en la práctica diaria, de los resultados de los avances en materia de investigación clínica. Objetivos: caracterizar el uso de la medicina basada en la evidencia en el acto de la prescripción. Métodos: se realizó un estudio descriptivo de corte transversal, en el primer nivel de asistencia médica. Se incluyeron de manera aleatoria 9 provincias del país (Santiago de Cuba, Camagüey, Matanzas, Holguín, Pinar del Río, La Habana, Ciego de Ávila, Granma y Guantánamo) que constituyen el 60 % y de estas el 25 % de los policlínicos (82). La selección de estos se realizó por un muestreo aleatorio simple con el programa estadístico EPIDAT. Se incluyó 765 prescriptores que prestaban servicios en las áreas seleccionadas en el momento de la aplicación del instrumento. Para la recogida de la información se diseñó un cuestionario "Prescribir con evidencia científica", con el objetivo de capturar toda la información relativa a las variables definidas. Resultados: más de la mitad de los encuestados (442) expresó que sientían la necesidad de buscar información frecuentemente; esta aumentó en los profesionales con experiencia, aunque la frecuencia anual con que lo hacen es baja, con un promedio de 6,48 veces al año y una moda de cero. Las interacciones medicamentosas fueron los aspectos de la prescripción acerca de los cuales los encuestados refirieron tener más dudas (69,4 %). Conclusiones: la mitad de los encuestados señaló que sientían frecuentemente la necesidad de consultar publicaciones científicas para dar respuesta a dudas relacionadas con el acto de la prescripción; sin embargo, la fuente que más empleron fueron los libros impresos y los cursos de actualización. Las interacciones y las reacciones adversas, fueron los aspectos sobre los que habitualmente buscan información, aunque refieren con mayor frecuencia tomar en cuenta la disponibilidad del fármaco en el momento de la prescripción.<br>Introduction: evidence-based medicine is a natural response to the need of creating a healthcare model that allows the integration of the results of the advances in clinical research into daily practice. Objectives: To characterize the use of evidence-based medicine in the act of prescribing. Methods: We conducted a cross sectional study in the first level of care. We included, at random, 9 provinces (Santiago de Cuba, Havana, Matanzas, Pinar del Rio, Camagüey, Ciego de Avila, Holguín, Granma and Guantanamo) that constitute 60 % and of these, 25 % of the clinics (82). The selection of these was by simple random sampling with the statistical program EPIDAT. 765 prescribers were included since they were serving in the selected areas at the time of the application of this instrument. For the collection of information a questionnaire "Prescribing scientific evidence" was designed in order to capture all the information on the variables defined. Results: Over half of respondents (442) noted that often feel the need to seek information, this necessity increases when less time professional experience, although the frequency of seeking for more information is annually low, with an average of 6, 48 times a year and a mode of zero. Concerning prescriptions, the respondents reported having more questions (69.4 %) about drug interactions. Conclusions: Half of the respondents stated that they often feel a need for review of scientific literature to answer questions during the act of prescribing. However, the sources they use are printed and updating courses. Interactions and adverse reactions are the aspects that they usually seek about, but they refer they often take into account the availability of the drug at the time of prescribing

Original Communication - Capillaroscopy in Fabry disease: Study of a family

Background: Nail bed capillaroscopy represents a simple and innocuous diagnosis method, used in vasculitis or collagen diseases. In Fabry disease (FD), there is a vasculopathy due to the storage of globotriaosylceramide. This is the first series that studies capillaroscopy in FD. Objective: To describe and evaluate the capillary findings in Fabry patients. Materials and Methods: Eight Fabry patients were selected; five were under enzyme replacement therapy (ERT) with agalsidase-A. Results: In three patients (under ERT), the capillaroscopy showed no abnormalities; two patients had absence of some capillaries (one with ERT); in three (one with ERT) the capillaroscopy revealed ramification of capillaries. Patients with normal capillaroscopy had no symptom of acroparesthesia for more than a year. Conclusions: Capillaroscopy is a good method to evaluate small vessels in FD and seems to have a correlation with ERT benefits, clinical manifestations and capillary findings. We purpose to use the capillaroscopy in the study of Fabry patients