Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.

Background: The Bari-SolidAct randomized controlled trial compared baricitinib with placebo in patients with severe COVID-19. A post hoc analysis revealed a higher incidence of serious adverse events (SAEs) among SARS-CoV-2-vaccinated participants who had received baricitinib. This sub-study aimed to investigate whether vaccination influences the safety profile of baricitinib in patients with severe COVID-19.

A novel tubular model to recapitulate features of distal airways: the bronchioid.

Background: Airflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerous models of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.

Lower airway microbiota compositions differ between influenza, COVID-19 and bacteria-related acute respiratory distress syndromes.

Background: Acute respiratory distress syndrome (ARDS) is responsible for 400,000 deaths annually worldwide. Few improvements have been made despite five decades of research, partially because ARDS is a highly heterogeneous syndrome including various types of aetiologies. Lower airway microbiota is involved in chronic inflammatory diseases and recent data suggest that it could also play a role in ARDS.

Impaired balance between neutrophil extracellular trap formation and degradation by DNases in COVID-19 disease.

Background: Thrombo-inflammation and neutrophil extracellular traps (NETs) are exacerbated in severe cases of COVID-19, potentially contributing to disease exacerbation. However, the mechanisms underpinning this dysregulation remain elusive. We hypothesised that lower DNase activity may be associated with higher NETosis and clinical worsening in patients with COVID-19.

Impact of dexamethasone in severe COVID-19-induced acute kidney injury: a multicenter cohort study.

Background: Acute kidney injury (AKI) in intensive care unit (ICU) patients with severe COVID-19 is common (> 50%). A specific inflammatory process has been suggested in the pathogenesis of AKI, which could be improved by dexamethasone (DXM). In a small monocenter study (n = 100 patients), we reported a potential protective effect of DXM on the risk of AKI.

Critically ill patients with infective endocarditis, neurological complications and indication for cardiac surgery: a multicenter propensity-adjusted study.

Background: The benefit-risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not.

Methods: In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3.

Invasive group A streptococcal infections requiring admission to ICU: a nationwide, multicenter, retrospective study (ISTRE study).

Background: Group A Streptococcus is responsible for severe and potentially lethal invasive conditions requiring intensive care unit (ICU) admission, such as streptococcal toxic shock-like syndrome (STSS). A rebound of invasive group A streptococcal (iGAS) infection after COVID-19-associated barrier measures has been observed in children. Several intensivists of French adult ICUs have reported similar bedside impressions without objective data.

Bridging gut microbiota composition with extended-spectrum beta-lactamase Enterobacteriales faecal carriage in critically ill patients (microbe cohort study).

Background: The worldwide dissemination of extended spectrum beta-lactamase producing Enterobacteriales (ESBL-E) is of major concern. Microbiota may play a role in the host resistance to colonization with ESBL-E, but the underlying mechanisms remain unknown. We aimed to compare the gut microbiota composition between ESBL-producing E.

Lung Mycobiota α-Diversity Is Linked to Severity in Critically Ill Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide. The chronic course of COPD is frequently worsened by acute exacerbations (AECOPD). Mortality in patients hospitalized for severe AECOPD remains dramatically high, and the underlying mechanisms are poorly understood.

Efficacy of carbapenem vs non carbapenem β-lactam therapy as empiric antimicrobial therapy in patients with extended-spectrum β-lactamase-producing Enterobacterales urinary septic shock: a propensity-weighted multicenter cohort study.

Background: The rise in antimicrobial resistance is a global threat responsible for about 33,000 deaths in 2015 with a particular concern for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and has led to a major increase in the use of carbapenems, last-resort antibiotics.

Methods: In this retrospective propensity-weighted multicenter observational study conducted in 11 ICUs, the purpose was to assess the efficacy of non carbapenem regimen (piperacillin-tazobactam (PTZ) + aminoglycosides or 3rd-generation cephalosporin (3GC) + aminoglycosides) as empiric therapy in comparison with carbapenem in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) urinary septic shock. The primary outcome was Day-30 mortality.

Neonatal imprinting of alveolar macrophages via neutrophil-derived 12-HETE.

Resident-tissue macrophages (RTMs) arise from embryonic precursors, yet the developmental signals that shape their longevity remain largely unknown. Here we demonstrate in mice genetically deficient in 12-lipoxygenase and 15-lipoxygenase (Alox15 mice) that neonatal neutrophil-derived 12-HETE is required for self-renewal and maintenance of alveolar macrophages (AMs) during lung development. Although the seeding and differentiation of AM progenitors remained intact, the absence of 12-HETE led to a significant reduction in AMs in adult lungs and enhanced senescence owing to increased prostaglandin E production.

Central Nervous System Cryptococcosis in Patients With Sarcoidosis: Comparison With Non-sarcoidosis Patients and Review of Potential Pathophysiological Mechanisms.

Introduction: spp. infection of the central nervous system (CINS) is a devastating opportunistic infection that was historically described in patients with acquired immunodeficiency syndrome (AIDS). spp.

Gut bacteriobiota and mycobiota are both associated with Day-28 mortality among critically ill patients.

Introduction: Gut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients.

Plasma Markers of Neutrophil Extracellular Trap Are Linked to Survival but Not to Pulmonary Embolism in COVID-19-Related ARDS Patients.

Introduction: Coronavirus disease 2019 (COVID-19) can cause life-threatening acute respiratory distress syndrome (ARDS). Recent data suggest a role for neutrophil extracellular traps (NETs) in COVID-19-related lung damage partly due to microthrombus formation. Besides, pulmonary embolism (PE) is frequent in severe COVID-19 patients, suggesting that immunothrombosis could also be responsible for increased PE occurrence in these patients.

Training can't always lead to Olympic macrophages.

Although the memory capacity of innate immune cells, termed trained immunity (TI), is a conserved evolutionary trait, the cellular and molecular mechanisms involved are incompletely understood. One fundamental question is whether the induction of TI generates a homogeneous or heterogeneous population of trained cells. In this issue of the JCI, Zhang, Moorlag, and colleagues tackle this question by combining an in vitro model system of TI with single-cell RNA sequencing.

Clinical trajectories and impact of acute kidney disease after acute kidney injury in the intensive care unit: a 5-year single-centre cohort study.

Background: Patients suffering from acute kidney injury(AKI) in the intensive care unit (ICU) can have various renal trajectories and outcomes. Aims were to assess the various clinical trajectories after AKI in the ICU and to determine risk factors for developing chronic kidney disease (CKD).

Methods: We conducted a prospective 5-year follow-up study in a medical ICU at Bordeaux University Hospital (France).

Complement Blockade Is a Promising Therapeutic Approach in a Subset of Critically Ill Adult Patients with Complement-Mediated Hemolytic Uremic Syndromes.

Thrombotic microangiopathy (TMA) gathers consumptive thrombocytopenia, mechanical haemolytic anemia, and organ damage. Hemolytic uremic syndromes (HUS) are historically classified as primary or secondary to another disease once thrombotic thrombocytopenic purpura (TTP), Shiga-toxin HUS, and cobalamin C-related HUS have been ruled out. Complement genetics studies reinforced the link between complement dysregulation and primary HUS, contributing to reclassifying some pregnancy- and/or post-partum-associated HUS and to revealing complement involvement in severe and/or refractory hypertensive emergencies.

High-resolution Free-breathing late gadolinium enhancement Cardiovascular magnetic resonance to diagnose myocardial injuries following COVID-19 infection.

Purpose: High-resolution free-breathing late gadolinium enhancement (HR-LGE) was shown valuable for the diagnosis of acute coronary syndromes with non-obstructed coronary arteries. The method may be useful to detect COVID-related myocardial injuries but is hampered by prolonged acquisition times. We aimed to introduce an accelerated HR-LGE technique for the diagnosis of COVID-related myocardial injuries.