miRNA as biomarker in lung cancer

Lung cancer has a high prevalence and mortality due to its late diagnosis and limited treatment, so it is essential to find biomarkers that allow a faster diagnosis and improve the survival of these patients. In this sense, biomarkers based on miRNAs have supposed a considerable advance. miRNAs, which are small RNA sequences, can regulate gene expression, so they play an essential role not only as a diagnostic biomarker but also as a therapeutic and prognostic one. Also, miRNA biomarkers can be obtained from liquid biopsies, which are less intrusive than lung biopsies, and have better accessibil-ity, safety and repeatability, which allows using those biomarkers both for diagnosis and monitoring of patients. In this review, we highlight the importance of miRNAs and collect the existing evidence of their relationship with lung cancer.Funding for open access charge: Universidad de Málaga / CBUA Funding for open access publishing: Universidad Málaga / CBU

Técnicas de detención del Sars Cov 2

Biomarkers are biological molecules widely used to determine disease stages. Clinical diagnostic tests in the SARS-CoV-2 infection, both  direct  and indirect,  rely  on biomarkers. Direct  biomarkers are  based  on  the identification of viral genome sequences, such as RT-qPCR diagnostics, those based on CRISPR-Cas9 systems, or direct sequencing  of  the  viral  genome  by  nanopores  (LampPORE).  Indirect  tests  are  based on the identification of biomarkers in response  to the disease, such as serological  tests, where  IgM and      IgG are identified. Ongoing, new test based on biosensors, differences in the metabolic status of the tissue, computer-assisted study of radiological images, or salivary sampling, become a new paradigm. Having faster diagnostic tests will enable to trace the evolution of the disease in the population, so its use is essential.Los biomarcadores son moléculas biológicas ampliamente utilizadas para determinar el estado de una enfermedad y están siendo la base de las pruebas de diagnóstico clínico, tanto directas como indirectas, de la infección por SARS-CoV-2. Los biomarcadores directos se basan en la identificación de secuencias del genoma del virus, como los diagnósticos por RT-qPCR, por CRISPR-Cas9, o por secuenciación directa del genoma del virus en nanoporos (LampPORE). Las determinaciones indirectas se basan en la identificación de biomarcadores en respuesta a la enfermedad, como las pruebas serológicas, donde se identifican las IgM e IgG. Un nuevo paradigma de detección aparece con el desarrollo de nuevas pruebas basadas en biosensores, en las diferencias en el estado metabólico del tejido, en el estudio de imágenes radiológicas asistido por ordenador, o incluso en tomar muestras de saliva. Tener pruebas de diagnóstico más rápi- das permitirá dibujar un mapa de la evolución de la enfermedad en la población, por lo que su uso es esencial

Genómica del cáncer de pulmón

In simplified terms, cancer consists of an uncontrolled proliferation of cells because proliferative signals are maintained and antiproliferative ones, such as cell death and immune response, are evaded. These cells also have angiogenic and metastatic capabilities, which confer the characteristic malignancy to cancer. When uncontrolled growth occurs in some type of cell in the respiratory system, we have lung cancer, which is considered a malignant tumor that invades neighboring structures and forms metastases in other tissues by spreading through the blood or lymph. In turn, the lung is a destination for metastases from other cancers unrelated to the respiratory systemDe forma simplificada, un cáncer consiste en una proliferación incontrolada de células debido a que se mantienen las señales proliferativas y se eluden las antiproliferativas, como la muerte celular y la respuesta inmunitaria. Éstas células también tienen capacidad angiogénica y metastásica, y son las que confieren al cáncer su malignidad característica. Cuando elcrecimiento incontrolado se produce en algún tipo de célula del aparato respiratorio, tenemos un cáncer de pulmón, que se considera un tumor maligno que invade las estructuras vecinas y forma metástasis en otros tejidos al diseminarse por la sangre o la linfa. A su vez, el pulmón es destino de metástasis de otros cánceres ajenos al aparato respiratorio

Clinical Audits in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Methodological Considerations and Workflow

Objectives: Previous clinical audits for chronic obstructive pulmonary disease (COPD) have provided valuable information on the clinical care delivered to patients admitted to medical wards because of COPD exacerbations. However, clinical audits of COPD in an outpatient setting are scarce and no methodological guidelines are currently available. Based on our previous experience, herein we describe a clinical audit for COPD patients in specialized outpatient clinics with the overall goal of establishing a potential methodological workflow.Methods: A pilot clinical audit of COPD patients referred to respiratory outpatient clinics in the region of Andalusia, Spain (over 8 million inhabitants), was performed. The audit took place between October 2013 and September 2014, and 10 centers (20% of all public hospitals) were invited to participate. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The usefulness of formally scheduled regular follow-up visits was assessed. Two different databases (resources and clinical database) were constructed. Assessments were planned over a year divided by 4 three-month periods, with the goal of determining seasonal-related changes. Exacerbations and survival served as the main endpoints.Conclusions: This paper describes a methodological framework for conducting a clinical audit of COPD patients in an outpatient setting. Results from such audits can guide health information systems development and implementation in real-world settings.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain)

Biomarcadores de cáncer de pulmón basados en la expresión de genes, transportes y secuencias repetitivas.

El haber encontrado elementos comunes en ambos tipos histológicos indica que su comportamiento transciende el cáncer concreto, por lo que podrían resultar útiles para confirmar diagnósticos. Se han propuesto parejas de genes y transposones próximos en las que ambos elementos aparecen diferencialmente expresados en el mismo sentido: 16 parejas en adenocarcinoma, y 36 en microcítico, siendo tres parejas comunes a ambos tipos histológicos (AluY - LONRF3, L1PA3 - AC007743.1, y LTR10A - ATF7IP2). Estas parejas comunes, que además cambian de expresión en el mismo sentido en todos los pacientes y enfermedades, podrían servir para determinar qué tienen en común los distintos tipos de cáncer de pulmón y también podrían ser útiles como biomarcadores universales. También se han propuesto tres genes con capacidad diagnóstica y pronóstica en adenocarcinoma (TMC5, CAPN8-2 y MUC1) y tres con utilidad diagnóstica en microcítico (ADYCAP1, BMX y TUBA1A). También se ha demostrado la utilidad de detectar los biomarcadores en cohortes pequeñas y verificarlos en cohortes grandes de las bases de datos. Finalmente, pensando en la futura aplicación clínica, se proponen genes de referencia (RPL14, ATP5F1A-202, UBA52, HNRN-PA1P54 y otros) para análisis de RT-PCR o en los que no se cuente con tejido sano con el que comparar. Fecha de lectura de Tesis Doctoral: 26 de septiembre de 2019Uno de los grandes avances terapéuticos es la medicina personalizada, que se basa en biomarcadores que ayudan en la filiación y elección del tratamiento. La mayoría de los biomarcadores se basan en variaciones génicas y solo recientemente se está prestando atención a la expresión diferencial de los genes codificantes que suponen solo un 2% del genoma humano. En cambio, el 45\% del genoma está formado por las secuencias repetitivas y transposones que han sido poco estudiados como biomarcadores debido a la dificultad de su secuenciación y análisis. Esta tesis contribuye a la búsqueda de biomarcadores usando datos generados a partir de la ultrasecuenciación del transcriptoma completo de tejido sano y tumoral de la misma persona, para que los resultados dependan solo la enfermedad y no del individuo. Las muestras se han obtenido a partir de las secuencias albergadas en bases de datos públicas (50 pacientes de adenocarcinoma y 17 de cáncer microcítico) y a partir de la secuenciación de muestras ultracongeladas de tejido sano y tumoral de pacientes operados en el Hospital Regional Universitario de Málaga (8 pacientes de adenocarcinoma y 8 pacientes de epidermoide), de los que se han generado de media más de 60 millones de lecturas por muestra. Se han diseñado dos nuevos flujos de trabajo bioinformáticos para la búsqueda de biomarcadores en genes, secuencias repetitivas y transposones, y para analizar la colocalización de genes y transposones. Entre los elementos repetitivos que se proponen como biomarcadores encontramos HERVK10D-Int sobreexpresado en adenocarcinoma y no en microcítico, y UCON88 sobreexpresado en microcítico y sin presentar expresión en adenocarcinoma, y tres (HERVL18-int, AluYg6 y LTR18B) con expresión diferencial en el mismo sentido en ambos tipos histológicos de cáncer

Construction of miRNA-mRNA networks for the identification of lung cancer biomarkers in liquid biopsies.

Lung cancer (LC) is the most common cause of cancer death worldwide mostly due to the low survival rate: 75% of cases are identified in advanced stages. In this study, the list of useful biomarkers to make an early diagnosis using liquid biopsies was expanded. A total of 30 samples of LC were analyzed to define potential miRNA biomarkers in liquid biopsies for LC. The biomarkers have been identified in interaction networks miRNA-mRNA. The potential biomarkers have been then validated in large cohorts. A total of 15 candidate miRNAs, that regulate the repression of 30 mRNAs, have been identified as a specific functional interaction network for squamous carcinoma, while the specific functional interaction network of adenocarcinoma consists of four candidate miRNAs that seem to handle the repression of five mRNA. Inspection of expression levels in larger cohorts validates the usefulness of the 11 candidates as biomarkers in liquid biopsies. The 11 candidate miRNAs found could be utilized to form diagnostic predictive biomarkers for LC in liquid biopsies

Guideline Adherence in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Results from a Clinical Audit.

Journal ArticleOBJECTIVES Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions. The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit. METHODS This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit. The appropriateness of the performance was categorized as excellent (>80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (<20%). RESULTS During the audit, 621 clinical records were audited. Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy. The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations. CONCLUSIONS The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics. Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain).Ye

Determinants for changing the treatment of COPD: a regression analysis from a clinical audit.

Journal Article;INTRODUCTION This study is an analysis of a pilot COPD clinical audit that evaluated adherence to guidelines for patients with COPD in a stable disease phase during a routine visit in specialized secondary care outpatient clinics in order to identify the variables associated with the decision to step-up or step-down pharmacological treatment. METHODS This study was a pilot clinical audit performed at hospital outpatient respiratory clinics in the region of Andalusia, Spain (eight provinces with over eight million inhabitants), in which 20% of centers in the area (catchment population 3,143,086 inhabitants) were invited to participate. Treatment changes were evaluated in terms of the number of prescribed medications and were classified as step-up, step-down, or no change. Three backward stepwise binominal multivariate logistic regression analyses were conducted to evaluate variables associated with stepping up, stepping down, and inhaled corticosteroids discontinuation. RESULTS The present analysis evaluated 565 clinical records (91%) of the complete audit. Of those records, 366 (64.8%) cases saw no change in pharmacological treatment, while 99 patients (17.5%) had an increase in the number of drugs, 55 (9.7%) had a decrease in the number of drugs, and 45 (8.0%) noted a change to other medication for a similar therapeutic scheme. Exacerbations were the main factor in stepping up treatment, as were the symptoms themselves. In contrast, rather than symptoms, doctors used forced expiratory volume in 1 second and previous treatment with long-term antibiotics or inhaled corticosteroids as the key determinants to stepping down treatment. CONCLUSION The majority of doctors did not change the prescription. When changes were made, a number of related factors were noted. Future trials must evaluate whether these therapeutic changes impact clinically relevant outcomes at follow-up.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain).Ye

Seasonal variability in clinical care of COPD outpatients: results from the Andalusian COPD audit

OBJECTIVES: Clinical practice in chronic obstructive pulmonary disease (COPD) can be influenced by weather variability throughout the year. To explore the hypothesis of seasonal variability in clinical practice, the present study analyzes the results of the 2013-2014 Andalusian COPD audit with regard to changes in clinical practice according to the different seasons. METHODS: The Andalusian COPD audit was a pilot clinical project conducted from October 2013 to September 2014 in outpatient respiratory clinics of hospitals in Andalusia, Spain (8 provinces with more than 8 million inhabitants) with retrospective data gathering. For the present analysis, astronomical seasons in the Northern Hemisphere were used as reference. Bivariate associations between the different COPD guidelines and the clinical practice changes over the seasons were explored by using binomial multivariate logistic regression analysis with age, sex, Charlson comorbidity index, type of hospital, and COPD severity by forced expiratory volume in 1 second as covariates, and were expressed as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: The Andalusian COPD audit included 621 clinical records from 9 hospitals. After adjusting for covariates, only inhaler device satisfaction evaluation was found to significantly differ according to the seasons with an increase in winter (OR, 3.460; 95% CI, 1.469-8.151), spring (OR, 4.215; 95% CI, 1.814-9.793), and summer (OR, 3.371; 95% CI, 1.391-8.169) compared to that in autumn. The rest of the observed differences were not significant after adjusting for covariates. However, compliance with evaluating inhaler satisfaction was low. CONCLUSION: The various aspects of clinical practice for COPD care were found to be quite homogeneous throughout the year for the variables evaluated. Inhaler satisfaction evaluation, however, presented some significant variation during the year. Inhaler device satisfaction should be evaluated during all clinical visits throughout the year for improved COPD management.This study was funded by an unrestricted grant from Menarini, SpainYe