Identification of host endotypes using peripheral blood transcriptomics in a prospective cohort of patients with endocarditis.

Objectives: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis.

Mechanical Stretch Induces Senescence of Lung Epithelial Cells and Drives Fibroblast Activation by Paracrine Mechanisms.

Severe lung injury requiring mechanical ventilation may lead to secondary fibrosis. Senescence, a cell response characterized by cell cycle arrest and a shift towards a proinflammatory/profibrotic phenotype, is one of the involved mechanisms. Here, we explore the contribution of mechanical stretch as trigger of senescence of the respiratory epithelium and its link with fibrosis.

Calcium-activated Potassium Channels as Amplifiers of TRPV4-mediated Pulmonary Edema Formation in Male Mice.

Background: As a mechanosensitive cation channel and key regulator of vascular barrier function, endothelial transient receptor potential vanilloid type 4 (TRPV4) contributes critically to ventilator-induced lung injury and edema formation. Ca2+ influx via TRPV4 can activate Ca2+-activated potassium (KCa) channels, categorized into small (SK1-3), intermediate (IK1), and big (BK) KCa, which may in turn amplify Ca2+ influx by increasing the electrochemical Ca2+ gradient and thus promote lung injury. The authors therefore hypothesized that endothelial KCa channels may contribute to the progression of TRPV4-mediated ventilator-induced lung injury.

Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19.

The main objective of this study was to determine whether the common Y-haplogroups were be associated with the risk of developing severe COVID-19 in Spanish male. We studied 479 patients who required hospitalization due to COVID-19 and 285 population controls from the region of Asturias (northern Spain), They were genotyped for several polymorphisms that define the common European Y-haplogroups. We compared the frequencies between patients and controls aged ≤ 65 and >65 years.

Immunoglobulin genes and severity of COVID-19.

There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection.

Flow starvation during square-flow assisted ventilation detected by supervised deep learning techniques.

Background: Flow starvation is a type of patient-ventilator asynchrony that occurs when gas delivery does not fully meet the patients' ventilatory demand due to an insufficient airflow and/or a high inspiratory effort, and it is usually identified by visual inspection of airway pressure waveform. Clinical diagnosis is cumbersome and prone to underdiagnosis, being an opportunity for artificial intelligence. Our objective is to develop a supervised artificial intelligence algorithm for identifying airway pressure deformation during square-flow assisted ventilation and patient-triggered breaths.

Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities.

Whereas aging is a whole-organism process, senescence is a cell mechanism that can be triggered by several stimuli. There is increasing evidence that critical conditions activate cell senescence programs irrespective of patient's age. In this review, we briefly describe the basic senescence pathways and the consequences of their activation in critically ill patients.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron.

Preventing occludin tight-junction disruption via inhibition of microRNA-193b-5p attenuates viral load and influenza-induced lung injury.

Virus-induced lung injury is associated with loss of pulmonary epithelial-endothelial tight junction integrity. While the alveolar-capillary membrane may be an indirect target of injury, viruses may interact directly and/or indirectly with miRs to augment their replication potential and evade the host antiviral defense system. Here, we expose how the influenza virus (H1N1) capitalizes on host-derived interferon-induced, microRNA (miR)-193b-5p to target occludin and compromise antiviral defenses.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148).

Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study.

Background: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied.

Age-dependent effect of the IFIH1/MDA5 gene variants on the risk of critical COVID-19.

MDA5, encoded by the IFIH1gene, is a cytoplasmic sensor of viral RNAs that triggers interferon (IFN) antiviral responses. Common and rare IFIH1 variants have been associated with the risk of type 1 diabetes and other immune-mediated disorders, and with the outcome of viral diseases. Variants associated with reduced IFN expression would increase the risk for severe viral disease.

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic: a matched analysis.

Background: The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with coronavirus disease 2019 (COVID-19)-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior noninvasive respiratory support on outcomes.

Methods: This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICUs) participating in the CIBERESUCICOVID project.

Assessment of Regional Lung Ventilation with Positron Emission Tomography Using the Radiofluorinated Gas [F]SF: Application to an Animal Model of Impaired Ventilation.

Purpose: Clinical ventilation studies are primarily performed with computerized tomography (CT) and more often with single-photon emission Computerized tomography (SPECT) using radiolabelled aerosols, both presenting certain limitations. Here, we investigate the use of the radiofluorinated gas [F]SF as a positron emission tomography (PET) ventilation marker in an animal model of impaired lung ventilation.

Procedures: Sprague-Dawley rats (n = 15) were randomly assigned to spontaneous ventilation (sham group), endotracheal administration of phosphate-buffered saline (PBS group), or endotracheal administration of lipopolysaccharide (LPS group).

Common mitochondrial haplogroups as modifiers of the onset-age for critical COVID-19.

As a key regulator of innate immunity, mitochondrial function is essential to maintain antiviral activities. Common mitochondrial DNA variants (haplogroups) have been associated with different physiological capacities and the nrisk of developing several diseases. Haplogroup H was associated with increased survival among sepsis patients, and lower risk of progression toward AIDS in HIV infected and lower manifestation of severe manifestation of herpex virus disease.

Transcriptomic clustering of critically ill COVID-19 patients.

Background: Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause a severe disease, termed coronavirus disease 2019 (COVID-19), with significant mortality. Host responses to this infection, mainly in terms of systemic inflammation, have emerged as key pathogenetic mechanisms and their modulation has shown a mortality benefit.

Methods: In a cohort of 56 critically ill COVID-19 patients, peripheral blood transcriptomes were obtained at admission to an intensive care unit (ICU) and clustered using an unsupervised algorithm.

IGHG3 hinge length variation was associated with the risk of critical disease and death in a Spanish COVID-19 cohort.

IgG3 would play an important role in the immune adaptive response against SARS-CoV-2, and low plasma levels might increase the risk of COVID-19 severity and mortality. The IgG3 hinge sequence has a variable repeat of a 15 amino acid exon with common 4-repeats (M) and 3-repeats (S). This length IGHG3 polymorphism might affect the IgG3 effector functions.

Genetic variants in the NF-κB signaling pathway (NFKB1, NFKBIA, NFKBIZ) and risk of critical outcome among COVID-19 patients.

The NF-κB signaling pathway is a key regulator of inflammation in the response to SARS-CoV-2 infection. This pathway has been implicated in the hyperinflammatory state that characterizes the severe forms of COVID-19. The genetic variation of the NF-κB components might thus explain the predisposition to critical outcomes of this viral disease.

Major candidate variables to guide personalised treatment with steroids in critically ill patients with COVID-19: CIBERESUCICOVID study.

Purpose: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19.

Methods: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs.

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study.

Background: The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae.

Methods: Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals.

Methodology of a Large Multicenter Observational Study of Patients with COVID-19 in Spanish Intensive Care Units.

Introduction: The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call.