Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Examining Profiles and Treatment Outcomes in Dual Diagnosis: Comparison of Coordinated Treatment With Mental Health Services Versus Addiction Center Alone. A Real-World Data Analysis.

OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.

Clinical and economic outcomes of a systematic same-day discharge programme after pulmonary vein isolation: comparison between cryoballoon vs. radiofrequency ablation.

AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.

Coordinated treatment between addiction and mental health services vs. uncoordinated treatment for patients with dual diagnosis: higher dropout rates but lower impairement of functional disability.

Dual pathology is often found in addiction and mental health centers. Although there are integrated services for these patients, most countries have developed joint action protocols between addiction and mental health centers. The objective is to analyze the progress of patients diagnosed with dual pathology, comparing the therapeutic outcomes of those who exclusively attend either addiction or mental health centers with those patients who follow a program in which the two services are coordinated. It is hypothesized that patients assisted in coordinate manner will present a better evolution on psychopathological symptomatology, drug use and functional impairment.

The Role of Anxiety in Patients With Persistent Atrial Fibrillation Undergoing Elective Cardioversion: An Observational Study.

OBJECTIVE: Anxiety is often present among patients with atrial fibrillation (AF). This condition has been associated with greater symptom severity and worse quality of life in these patients. However, the influence of anxiety on the risk of AF recurrence is not well known. We aimed to define the level of anxiety in patients with persistent AF undergoing elective cardioversion (EC) and determine whether there is an association between anxiety and the risk of early AF recurrence after EC. METHODS: Anxiety was measured before EC using the State-Trait Anxiety Inventory. Early AF recurrence was assessed with a control electrocardiogram at 30-day follow-up. RESULTS: We included 107 patients undergoing effective EC. Early AF recurrence was diagnosed in 40 patients (37.4%). Compared with those who remained in sinus rhythm, individuals with early AF recurrence had significantly higher levels of trait anxiety (23.1 [10.4] versus 17.9 [9.5]; p = .013) and larger left atrial volume index (45.8 [12.3] versus 37.9 [13.3] ml/m; p = .004). Both variables remained independently associated with early AF recurrence after multivariate analysis. A predictive model including trait anxiety score >20 and left atrial volume index >41 ml/m showed acceptable accuracy for the diagnosis of early AF recurrence (area under the curve = 0.733; 95% confidence interval = 0.634-0.832; p < .001). CONCLUSIONS: Our study shows that trait anxiety is an independent risk factor for early AF recurrence after EC. Further studies are warranted to assess the beneficial role of anxiety-reducing strategies on the outcomes of patients with AF.

Adaptive biokinetic modelling of iodine-131 in thyroid cancer treatments: implications on individualised internal dosimetry.

Nowadays therapies involving radioiodine (I-131) represent 84% of the total metabolic treatments in Europe, according to the last report of the European Association of Nuclear Medicine in relation to treatment planning for molecular radiotherapy. Last recommendations of the European Council, i.e. 2013/59/Euroatom, mandates that metabolic treatments should be planned according to the radiation doses delivered to individual patients, analogous to external beam radiotherapy. In this work, we present a novel biokinetic model for I-131 that allows on to obtain realistic activity distributions for particular patients with thyroid cancer in absence of metastasis. Other models existing in the literature present either a too simple metabolic description to obtain realistic results or a too complex one for adapting the model to individual patients, and many of these models are not indicated for metabolic treatments. The individualisation of activity distribution is obtained by an optimisation method that adjusts our model to a set of experimental measurements. Significant differences in terms of absorbed doses are observed between our model and the standard generalist models, especially in terms of red marrow absorbed dose.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

Outcomes of a 24/7 service for urgent permanent pacemaker implantation.

INTRODUCTION AND OBJECTIVES: Most of the complications associated with acute and symptomatic bradyarrhythmia (ASB) occur in the time from diagnosis to permanent pacemaker implantation (PPI). We aimed to evaluate the outcomes of an urgent 24/7 PPI service (PPI-24/7) for patients with ASB. METHODS: A total of 664 patients undergoing first-time PPI for ASB were prospectively assessed during 2 periods of identical length (18 months): 341 patients who underwent the procedure during working hours only (PPI-WH), and 323 patients who underwent the procedure after the implementation of the PPI-24/7 service. The primary safety endpoint was established as the cumulative 180-day incidence of complications related to the index arrhythmia and device implant. The primary efficacy endpoint was determined as the average number of hospital stays per patient. RESULTS: The PPI-24/7 period was associated with a significant shortening of the time from diagnosis to implantation (median [interquartile range]): 3hours [2-6] vs 16 [5-21]). The cumulative incidence of patients with complications at 180 days was lower in the PPI-24/7 period: 9% vs 17% (adjusted odds ratio, 0.5; P=.002), due to a significant reduction in preimplant complications: 2.5% vs 12% (P <.001). The average number of hospital stays was reduced by 2 per patient in the PPI-24/7 period (nonparametric P <.001). PPI-24/7 implants performed outside working hours (n=178) were safe, with a 180-day cumulative incidence in procedure-related complications of 3.9%. CONCLUSIONS: Among patients with ASB, PPI-24/7 was associated with a significant reduction in patient morbidity and efficient hospital resource use.

The theory of planned behavior and alcohol protective behavioral strategies: a prospective study examining the role of habit and gender invariance.

OBJECTIVES: Alcohol Protective Behavioral Strategies (PBS) have consistently shown to be effective in reducing alcohol use and its associated consequences. We aimed to examine the explanatory value of the Theory of Planned Behavior (TPB) for using five PBS, studying the role of habit, and its potential variation across genders. METHODS: Targeted sampling was used to recruit 339 young adults in the community (women = 50.7%; mean age = 2.21[SD = 2.21]), who completed baseline and 2-month follow-up questionnaires. RESULTS: The explained variance of the TPB ranged from 58-68% for intention to use PBS, and 18-50% for behavior. The inclusion of habit produced increases of 17-26% in explained variance in intention, while explained variance in behavior remained similar. Habit was the strongest predictor of intention to use PBS, followed by attitude. Except for one behavior (drinking slowly), habits did not moderate the intention-behavior relationship, and the explanatory value of the TPB did not differ across genders. CONCLUSIONS: Our findings support the utility of the TPB as an explanatory model of alcohol PBS, along with the need to include habits within the framework of dual-process models. Interventions aimed at promoting alcohol PBS could be optimized by targeting attitudes towards PBS and habits.

Comparison of Different Sexual Behaviors According to Sexual Orientation and the Mediating Role of Attitudes toward Sexual Behaviors between Sexual Orientation and Sexual Behaviors in Young Adults.

Objectives: To explore the relationship between sexual orientation and specific sexual and risk behaviors, compare the number of sexual behaviors and attitudes among people of different sexual orientations, and test the mediating effect of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors. Methods: A total of 2288 participants completed a checklist of sexual behaviors, indicators of sexual risk behaviors, and a scale of attitudes toward sexual behaviors. Results: Bisexual women engaged in a greater number of sexual behaviors and had more positive attitudes toward sexual behaviors than heterosexual women. Homosexual men engaged in a greater number of sexual behaviors than heterosexual men, and homosexual and bisexual men had more positive attitudes toward sexual behaviors than heterosexuals. Finally, we show the mediating role of attitudes toward sexual behaviors in the relationship between sexual orientation and the number of sexual behaviors engaged in. Conclusions: The importance of considering sexual orientation when analyzing sexual behaviors and attitudes is highlighted.

Operational definitions and measurement of externalizing behavior problems: An integrative review including research models and clinical diagnostic systems.

Measurement of externalizing disorders such as antisocial disorders, attention-deficit/hyperactivity disorder or borderline disorder have relevant implications for the daily lives of people with these disorders. While the Diagnostic and Statistical Manual of Mental Disorders (DSM) and the International Classification of Diseases (ICD) have provided the diagnostic framework for decades, recent dimensional frameworks question the categorical approach of psychopathology, inherent in traditional nosotaxies. Tests and instruments develop under the DSM or ICD framework preferentially adopt this categorical approach, providing diagnostic labels. In contrast, dimensional measurement instruments provide an individualized profile for the domains that comprise the externalizing spectrum, but are less widely used in practice. Current paper aims to review the operational definitions of externalizing disorders defined under these different frameworks, revise the different measurement alternatives existing, and provide an integrative operational definition. First, an analysis of the operational definition of externalizing disorders among the DSM/ICD diagnostic systems and the recent Hierarchical Taxonomy of Psychopathology (HiTOP) model is carried out. Then, in order to analyze the coverage of operational definitions found, a description of measurement instruments among each conceptualization is provided. Three phases in the development of the ICD and DSM diagnosis systems can be observed with direct implications for measurement. ICD and DSM versions have progressively introduced systematicity, providing more detailed descriptions of diagnostic criteria and categories that ease the measurement instrument development. However, it is questioned whether the DSM/ICD systems adequately modelize externalizing disorders, and therefore their measurement. More recent theoretical approaches, such as the HiTOP model seek to overcome some of the criticism raised towards the classification systems. Nevertheless, several issues concerning this model raise mesasurement challenges. A revision of the instruments underneath each approach shows incomplete coverage of externalizing disorders among the existing instruments. Efforts to bring nosotaxies together with other theoretical models of psychopathology and personality are still needed. The integrative operational definition of externalizing disorders provided may help to gather clinical practice and research.

Spontaneous Variation of Ventriculo-Atrial Interval after Tachycardia Induction: Determinants and Usefulness in the Diagnosis of Supraventricular Tachycardias with Long Ventriculoatrial Interval.

Background: Determining the mechanism of supraventricular tachycardias with prolongedP ventriculoatrial (VA) intervals is sometimes a challenge. Our objective is to analyse the determinants, time course and diagnostic accuracy (atypical atrioventricular nodal reentrant tachycardias [AVNRT] versus orthodromic reentrant tachycardias through an accessory pathway [ORT]) of spontaneous VA intervals variation in patients with narrow QRS tachycardias and prolonged VA. Methods: A total of 156 induced tachycardias were studied (44 with atypical AVNRT and 112 with ORT). Two sets of 10 measurements were performed for each patient­after tachycardia induction and one minute later. VA and VV intervals were determined. Results: The difference between the longest and the shortest VA interval (Dif-VA) correlates significantly with the diagnosis of atypical AVNRT (C coefficient = 0.95 and 0.85 after induction and at one minute, respectively; p < 0.001). A Dif-VA ≥ 15 ms presents a sensitivity and specificity for atypical AVNRT of 50% and 99%, respectively after induction, and of 27% and 100% one minute later. We found a robust and significant correlation between the fluctuations of VV and VA intervals in atypical AVNRTs (Coefficient Rho: 0.56 and 0.76, after induction and at one minute, respectively; p < 0.001 for both) but not in ORTs. Conclusions: The analysis of VA interval variability after induction and one minute later correctly discriminates atypical AVNRT from ORT in almost all cases.

Psychometric properties of the Spanish adaptation of the Externalizing Spectrum Inventory-Brief Form (ESI-BF).

The Externalizing Spectrum Inventory-Brief Form (ESI-BF) measures tendencies toward disinhibition, lack of control, aggression, and substance use. This study adapts the ESI-BF to the Spanish population and assesses its psychometric properties. The study included 742 community adults obtained by stratified random sampling with proportional allocation according to gender, age, and geographical area of the Spanish territory and a clinical sample consisting of 333 patients. All participants completed the Personality Inventory for Diagnostic and Statistical Manual of Mental Disorders, fifth edition (PID-5) and the Alcohol Substance Dependence Severity Scale, in addition to the Spanish version of the ESI-BF. Reliability was quantified using McDonald's omega and Cronbach's α reliability coefficients. Validity evidences were studied applying confirmatory factor analysis (CFA) and correlations. Results indicated adequate reliability of scores on the ESI-BF's general factors and most of its facets. Regarding internal structure, and in line with previous studies, both symmetric and S-1 hierarchical two-subfactor (bifactor) emerged as the best-fitting models. Considering both criticisms of symmetric models and parsimony, the S-1 bifactor model, which showed configural invariance across gender and samples, was retained. Validity evidence based on the relationship with other measures of personality and alcohol consumption show correlations values theoretically expected in both clinical and community samples. Findings suggest that the Spanish adaptation of the ESI-BF shows functional near-equivalence to the original version. Its effective psychometric properties make it useful instrument for further research related to the externalizing spectrum. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Retention in treatment and therapeutic adherence: How are these associated with therapeutic success? An analysis using real-world data.

INTRODUCTION: Treatment retention and adherence are used as outcomes in numerous randomized clinical trials and observational studies conducted in the addiction field. Although usual criteria are 3/6 months of treatment retention or number of sessions attended, there is not a methodological support for conclusions using these criteria. This study analyzed the usefulness of retention and adherence to predict therapeutic success. METHODS: Retrospective observational study using real-world data from electronic health records of 11,907 patients in treatment diagnosed with cocaine, alcohol, cannabis and opiate use disorders or harmful use. RESULTS: Moderate effect size relations were found between the different type of clinical discharge and months in retention (η2  = 0.12) and proportion of attendance (η2  = 0.10). No relationship was found with the number of sessions attended. Using cut-off points (i.e., 3 or 6 months in treatment or attending 6 therapy sessions) worsens the ability to predict the type of discharge. DISCUSSIONS/CONCLUSION: Treatment retention and adherence are indicators moderately related to therapeutic success. Research using these indicators to assess the effectiveness of therapies should complement their results with other clinical indicators and quality of life measures.

Benefits of cardiac pacing in ICD recipients with hypertrophic cardiomyopathy.

PURPOSE: Implantable cardiac defibrillator (ICD) is the only definitive therapy for prevention of sudden cardiac death in hypertrophic cardiomyopathy (HCM). Conventional transvenous ICDs can provide cardiac pacing unlike new subcutaneous ICD, but the usefulness of cardiac pacing in HCM patients is not well defined. We sought to assess the usefulness of ICD pacing in HCM. METHODS: We retrospectively analyzed 93 HCM patients who had undergone ICD implantation at our center. Usefulness of pacing was defined as follows: 1) need of pacing due to bradycardia or AV conduction disturbances, 2) improvement of LV outflow tract obstruction by sequential AV pacing, 3) need for CRT pacing, or 4) successful antitachycardia pacing without a subsequent shock. Independent predictors of useful pacing were investigated by multivariable analysis. RESULTS: During a mean follow-up of 91.3 ± 5.5 months, 43 patients (46.2%) reached the composite endpoint. Independent predictors of pacing usefulness were older age (HR 1.36; 95%CI: 1.088-1.709; p=0.007) and NYHA functional class ≥ II (HR 2.15; 95%CI: 1.083-4.301; p=0.029). Twenty-eight (30.1%) patients had appropriate ICD interventions, triggered by a monomorphic ventricular tachycardia (MVT) in 22 of them (78.5%). In 17 individuals with MVT (77%), antitachycardia pacing successfully treated MVT. CONCLUSIONS: In our HCM series of patients with ICD, 46% of individuals benefitted from cardiac pacing. MVT were documented in nearly 80% of the patients with ventricular arrhythmias and antitachycardia pacing successfully treated them in 77% of cases.

Norms According to Age and Gender for the Spanish Version of the Inventory of Depression and Anxiety Symptoms (IDAS-II).

Inventory of Depression and Anxiety Symptoms-II (IDAS-II) constitutes a useful measurement tool with demonstrated psychometric properties that is contributing to the advancement of knowledge of emotional disorders within transdiagnostic models. To implement its use in clinical settings it is important that the scores can be interpreted in order to guide clinical decisions. This study aims to develops normative data for the Spanish version of the IDAS-II. An anonymous online survey was applied to 1,072 subjects, recruited through a stratified random sampling procedure taking into account population gender, age, and geographical region of Spain. Results show that women tend to score higher than men, particularly on the Dysphoria, General Depression, Appetite Gain, and Lassitude scales. Largest effect sizes for differences in the scores according to age were found for Lassitude, Dysphoria, and General Depression. Therefore, normative data according to gender and age group for each IDAS-II scale is provided. The norms provided in this work complement those already available, facilitating the decision-making of clinical professionals. Evidence of unidimensionality is provided for the 19 IDAS-II scales that allows researchers and clinicians to use specific IDAS-II scales independently.

Hypoxia compromises the mitochondrial metabolism of Alzheimer's disease microglia via HIF1.

Genetic Alzheimer's disease (AD) risk factors associate with reduced defensive amyloid ß plaque-associated microglia (AßAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AßAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AßAM clustering and proliferation and increases Aß neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aß plaque microglial coverage and an increase of Aß plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.

-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--.

Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.