Higher mortality and intubation rate in COVID-19 patients treated with noninvasive ventilation compared with high-flow oxygen or CPAP

COVID-19; Noninvasive ventilation; High-flow oxygenCOVID-19; Ventilación no invasiva; Oxígeno de alto flujoCOVID-19; Ventilació no invasiva; Oxigen d'alt cabalThe effectiveness of noninvasive respiratory support in severe COVID-19 patients is still controversial. We aimed to compare the outcome of patients with COVID-19 pneumonia and hypoxemic respiratory failure treated with high-flow oxygen administered via nasal cannula (HFNC), continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV), initiated outside the intensive care unit (ICU) in 10 university hospitals in Catalonia, Spain. We recruited 367 consecutive patients aged ≥ 18 years who were treated with HFNC (155, 42.2%), CPAP (133, 36.2%) or NIV (79, 21.5%). The main outcome was intubation or death at 28 days after respiratory support initiation. After adjusting for relevant covariates and taking patients treated with HFNC as reference, treatment with NIV showed a higher risk of intubation or death (hazard ratio 2.01; 95% confidence interval 1.32-3.08), while treatment with CPAP did not show differences (0.97; 0.63-1.50). In the context of the pandemic and outside the intensive care unit setting, noninvasive ventilation for the treatment of moderate to severe hypoxemic acute respiratory failure secondary to COVID-19 resulted in higher mortality or intubation rate at 28 days than high-flow oxygen or CPAP. This finding may help physicians to choose the best noninvasive respiratory support treatment in these patients.Clinicaltrials.gov identifier: NCT04668196

Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia:a systematic review and individual participant data meta-analysis

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks

Identificación de nuevos genes implicados en la iniciación y desarrollo de las raíces laterales en "Arabidopsis thaliana"

Las plantas son organismos sésiles que deben crecer en el medio donde germinan y adaptarse a las condiciones ambientales que les rodean. El sistema radicular es fundamental para su adaptación y eficiencia reproductiva, ya que es el órgano encargado de adquirir nutrientes y agua del medio. El incremento del sistema radicular está determinado por el número y posición de las raíces laterales. Entender cómo las plantas reorganizan su sistema radicular, permitirá obtener plantas que requieran una menor aportación de recursos. En este trabajo se han identificado nuevos genes implicados en la formación y desarrollo de las raíces laterales en “Arabidopsis thaliana” utilizando una estrategia genómica y otra genética. Con la primera, mediante una estrategia de “separación celular” y genómica, se han identificado más de 600 genes relacionados con este proceso y se ha analizado la función de un grupo de ellos que se seleccionaron en base a su expresión tisular. Mediante una estrategia genética, se ha identificado un mutante recesivo, “srol1”, que presenta un sistema radicular reducido dependiente de la calidad de la luz, del cual se ha llevado a cabo su caracterización fenotípica y molecular.Plants are sessile organisms that have to adapt their growth to the environment where they are obligated to live. To have an optimal adaptation, the root system plays a key role, because acquires the nutrients and water needed for the efficient growth and development of the plants. The growth of the root system is based on the length of the main root and on the number and disposition of the lateral roots. Understanding how plants can adapt (re-organize) their root system will allow us to get plants that require less input of resources. In this project we have identified new genes that are implicated in the lateral root formation and development in “Arabidopsis thaliana”. Using an approach based on the combination of specific cell sorting and transcriptomic we have identified over 600 genes that are involved in the development of the root system. We have analyzed the function of a set of these genes selected on bases of their tissue expression. Using a genetic approach, we have identified a recessive mutant, “srol1”, that shows a reduced root development that is dependent on the quality of the light perceived by the root system. We have carried out a phenotypic and molecular characterization of this mutant.Ministerio de Educación de España por financiar la Ayuda del Programa de Formación de Profesorado Universitario (FPU, Referencia AP2009-2351

Ventilación mecánica no invasiva domiciliaria: adaptación y seguimiento

Las enfermedades de caja torácica y neuromusculares son trastornos que representan una importante causa de insuficiencia respiratoria crónica hipercápnica. La ventilación mecánica no invasiva domiciliaria (VMNID) se considera el tratamiento de elección en estos pacientes cuando la insuficiencia respiratoria está establecida. El proceso de adaptación a la VMNID puede realizarse con el paciente ingresado o bien de forma ambulatoria. El hecho de que no existan estudios que demuestren la superioridad de una localización con respecto a otra, condiciona que la elección del lugar de adaptación se base en las preferencias de cada equipo instalador. Otro factor de gran interés y poco estudiado es la evolución a largo plazo de los pacientes con VMNID, y qué factores se asocian con la mortalidad. Los objetivos de esta tesis fueron comparar la eficacia y el coste que representa la adaptación de VMNID de forma ambulatoria, en relación a la adaptación con el paciente ingresado, en pacientes con insuficiencia respiratoria secundaria a enfermedades neuromusculares o a alteraciones de la caja torácica. Así como analizar la mortalidad y los factores pronósticos de una cohorte de pacientes con enfermedad de caja torácica tratados con VMNID. Para ello se realizaron dos estudios, un ensayo clínico randomizado multicéntrico que evaluó la eficacia mediante la presión parcial de anhídrido carbónico en sangre arterial (PaCO2) basal y a los seis meses de haber iniciado la VMNID en cada uno de los grupos de adaptación (ambulatoria y hospitalaria), así como los costes económicos de cada uno de los grupos. El segundo trabajo consistió en un estudio observacional prospectivo que analizó la mortalidad de una cohorte de pacientes con VMNID, y las posibles variables asociadas. Los principales resultados de los dos estudios realizados fueron que la adaptación ambulatoria a la VMNID no presenta diferencias en cuanto a eficacia respecto la adaptación hospitalaria en pacientes con insuficiencia respiratoria crónica secundaria a enfermedades neuromusculares o a alteraciones de la caja torácica, resultando además más barata y que una PaCO2 mayor o igual a 50 mmHg al mes de haber iniciado la VMNID y la presencia de comorbilidad son factores predictivos de mortalidad en pacientes con insuficiencia respiratoria crónica secundaria a enfermedades de caja torácica. Así pues se puede concluir que en la práctica clínica habitual la adaptación ambulatoria a la VMNID es una opción a considerar ya que puede representar un ahorro en los gastos sanitarios y que una vez el paciente esté adaptado a la VMNID, la PaCO2 al mes aporta información relevante que puede condicionar decisiones terapéuticas.Chest wall and neuromuscular diseases are common disorders which account for a major cause of hypercapnic chronic respiratory failure. Noninvasive home mechanical ventilation (NIHMV) is considered the treatment of choice in these patients when respiratory failure is well established. Adaptation process to NIHMV can be performed either in the hospital setting or ambulatory. Because few studies have evaluated the superiority of one setting over another for adapting to NIHMV, the choice has been based on the preferences or possibilities of each team of health professionals. Other essential factors of major interest, but poorly studied, are the long-term evolution of patients with NIHMV and variables associated with mortality. This thesis main objectives were to compare the effectiveness and costs of adaptation to NIHMV performed in the ambulatory or hospital setting in patients with chronic respiratory failure secondary to neuromuscular diseases or chest wall disorders. Another objective was to analyze mortality and prognostic factors of a cohort of patients with chest wall disease following NIHMV. In this thesis, two studies were conducted, a multicenter randomized clinical trial that evaluated the effectiveness using partial pressure of carbon dioxide in arterial blood (PaCO2) baseline and at six months following initiation of NIHMV in each adaptation group (outpatient and inpatient), as well as economic costs for each group. The second study was a prospective observational study that analyzed mortality, and its possible associated variables, in a cohort of patients with NIHMV. Both studies main results were that adaptation to NIHMV in the ambulatory setting is not inferior to hospital adaptation in terms of therapeutic equivalence in stable patients with chronic respiratory failure secondary to neuromuscular or chest wall diseases, and outpatient adaptation may represent a cost saving for the healthcare system. In addition, PaCO2 levels higher or equal to 50 mmHg at one month after starting NIHMV and the presence of comorbid conditions are risk factors for mortality in patients with chronic respiratory failure secondary to chest wall disease. As a conclusion, in routine clinical practice, outpatient adaptation to NIHMV remains an option to be considered since it may represent a cost saving for the healthcare system, and once the patient is adapted to NIHMV, PaCO2 at one moth provides relevant information that might help to set for therapeutic decisions

Identificación de nuevos genes implicados en la iniciación y desarrollo de las raíces laterales en "Arabidopsis thaliana"

Las plantas son organismos sésiles que deben crecer en el medio donde germinan y adaptarse a las condiciones ambientales que les rodean. El sistema radicular es fundamental para su adaptación y eficiencia reproductiva, ya que es el órgano encargado de adquirir nutrientes y agua del medio. El incremento del sistema radicular está determinado por el número y posición de las raíces laterales. Entender cómo las plantas reorganizan su sistema radicular, permitirá obtener plantas que requieran una menor aportación de recursos. En este trabajo se han identificado nuevos genes implicados en la formación y desarrollo de las raíces laterales en “Arabidopsis thaliana” utilizando una estrategia genómica y otra genética. Con la primera, mediante una estrategia de “separación celular” y genómica, se han identificado más de 600 genes relacionados con este proceso y se ha analizado la función de un grupo de ellos que se seleccionaron en base a su expresión tisular. Mediante una estrategia genética, se ha identificado un mutante recesivo, “srol1”, que presenta un sistema radicular reducido dependiente de la calidad de la luz, del cual se ha llevado a cabo su caracterización fenotípica y molecular.Plants are sessile organisms that have to adapt their growth to the environment where they are obligated to live. To have an optimal adaptation, the root system plays a key role, because acquires the nutrients and water needed for the efficient growth and development of the plants. The growth of the root system is based on the length of the main root and on the number and disposition of the lateral roots. Understanding how plants can adapt (re-organize) their root system will allow us to get plants that require less input of resources. In this project we have identified new genes that are implicated in the lateral root formation and development in “Arabidopsis thaliana”. Using an approach based on the combination of specific cell sorting and transcriptomic we have identified over 600 genes that are involved in the development of the root system. We have analyzed the function of a set of these genes selected on bases of their tissue expression. Using a genetic approach, we have identified a recessive mutant, “srol1”, that shows a reduced root development that is dependent on the quality of the light perceived by the root system. We have carried out a phenotypic and molecular characterization of this mutant.Ministerio de Educación de España por financiar la Ayuda del Programa de Formación de Profesorado Universitario (FPU, Referencia AP2009-2351

Poor sleep quality, COPD severity and survival according to CASIS and Pittsburgh questionnaires

Abstract Poor sleep quality is frequent among COPD patients and it has been related to worse outcomes. The objective of this study was to compare the COPD and Asthma Sleep Impact Scale (CASIS) and the generic Pittsburgh Sleep Quality Index (PSQI) questionnaires as reliable tools for evaluating sleep quality and its relationship with COPD characteristics and survival. Stable COPD patients were prospectively evaluated. Anthropometric, sociodemographic, comorbidity, lung function and treatment data were collected. All patients completed CASIS and PSQI, mMRC dyspnea severity scale, COPD Assessment Test (CAT), sleep apnoea STOP-Bang and Hospital Anxiety and Depression Scale (HADS) questionnaires. Body mass index, airflow Obstruction, Dyspnea and Exacerbations (BODEx) index was calculated. Life status was determined after a mean follow-up of 3.7 (SD 1) years. We included 200 patients, 69.5% male, mean age 65.8 (9) years. Poor sleep was detected in 100 (50%) and 84 patients (42%) according to PSQI and CASIS questionnaires, respectively, with an agreement of 63%. Poor sleep was related to female gender, more severe dyspnea and worse BODEx, HADS and CAT scores according to both questionnaires. PSQI was associated to chronic pain or inferior urinary tract symptoms and CASIS to exacerbations, shorter walked distance in the 6-min walking test and treatment with oral corticosteroids or chronic oxygen. Thirty nine (19.5%) patients died during follow-up. Mortality was not associated to PSQI nor CASIS results. Unlike PSQI, CASIS is more related to COPD severity and its results are not influenced by comorbidities with known impact on sleep quality. In our sample, poor sleep quality was not associated with increased mortality

Effect of Intensity of Home Noninvasive Ventilation in Individuals With Neuromuscular and Chest Wall Disorders: A Systematic Review and Meta-Analysis of Individual Participant Data

Introduction: Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD).Methods: Controlled, non-controlled and cohort studies indexed between January-2000 and December 2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO2, PaO2, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the Z-score of the product of pressure support (or tidal volume) and backup-rate.Results: 16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO2 was greater with higher baseline PaCO2. NIV intensity per se was not associated with improved PaCO2 except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO2. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found.Conclusion: Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO2, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy.& COPY; 2023 SEPAR. Published by Elsevier Espan & SIM;a, S.L.U. All rights reserved

Overexpression of a pine Dof transcription factor in hybrid poplars:A comparative study in trees growing under controlled and natural conditions

In this work, the role of the pine transcriptional regulator Dof 5 in carbon and nitrogen metabolism has been examined in poplar trees. The overexpression of the gene and potential effects on growth and biomass production were compared between trees growing in a growth chamber under controlled conditions and trees growing in a field trial during two growth seasons. Ten-week-old transgenic poplars exhibited higher growth than untransformed controls and exhibited enhanced capacity for inorganic nitrogen uptake in the form of nitrate. Furthermore, the transgenic trees accumulated significantly more carbohydrates such as glucose, fructose, sucrose and starch. Lignin content increased in the basal part of the stem likely due to the thicker stem of the transformed plants. The enhanced levels of lignin were correlated with higher expression of the PAL1 and GS1.3 genes, which encode key enzymes involved in the phenylalanine deamination required for lignin biosynthesis. However, the results in the field trial experiment diverged from those observed in the chamber system. The lines overexpressing PpDof5 showed attenuated growth during the two growing seasons and no modification of carbon or nitrogen metabolism. These results were not associated with a decrease in the expression of the transgene, but they can be ascribed to the nitrogen available in the field soil compared to that available for growth under controlled conditions. This work highlights the paramount importance of testing transgenic lines in field trials

The emerging role of reactive oxygen species signaling during lateral root development

Overall root architecture is the combined result of primary and lateral root growth and is influenced by both intrinsic genetic programs and external signals. One of the main questions for root biologists is how plants control the number of lateral root primordia and their emergence through the main root. We recently identified S-phase kinase-associated protein2 (SKP2B) as a new early marker for lateral root development. Here, we took advantage of its specific expression pattern in Arabidopsis (Arabidopsis thaliana) in a cell-sorting and transcriptomic approach to generate a lateral root-specific cell sorting SKP2B data set that represents the endogenous genetic developmental program. We first validated this data set by showing that many of the identified genes have a function during root growth or lateral root development. Importantly, genes encoding peroxidases were highly represented in our data set. Thus, we next focused on this class of enzymes and showed, using genetic and chemical inhibitor studies, that peroxidase activity and reactive oxygen species signaling are specifically required during lateral root emergence but, intriguingly, not for primordium specification itself. © 2014 American Society of Plant Biologists. All rights reserved