Innate immune response in acute critical illness: a narrative review.

Background: Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies.

Inadequate intensive care physician supply in France: a point-prevalence prospective study.

Background: The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation.

High Prevalence of the Lung Ultrasound Interstitial Syndrome in Systemic Sclerosis Patients with Normal HRCT and Lung Function-A Pilot Study.

High-resolution computed tomography (HRCT) may lack sensitivity for the early detection of interstitial lung disease associated with systemic sclerosis (SSc-ILD). Lung ultrasound is an emerging technique for the diagnosis of SSc-ILD. This cross-sectional study aimed to describe the prevalence of ultrasound interstitial syndrome in SSc patients with normal HRCT and pulmonary function tests (PFT).

The place of new antibiotics for Gram-negative bacterial infections in intensive care: report of a consensus conference.

Introduction: New beta-lactams, associated or not with beta-lactamase inhibitors (NBs/BIs), can respond to the spread of carbapenemase-producing enterobacteriales and nonfermenting carbapenem-resistant bacteria. The risk of emergence of resistance to these NBs/BIs makes guidelines necessary. The SRLF organized a consensus conference in December 2022.

The positive impact of COVID-19 on critical care: from unprecedented challenges to transformative changes, from the perspective of young intensivists.

Over the past 2 years, SARS-CoV-2 infection has resulted in numerous hospitalizations and deaths worldwide. As young intensivists, we have been at the forefront of the fight against the COVID-19 pandemic and it has been an intense learning experience affecting all aspects of our specialty. Critical care was put forward as a priority and managed to adapt to the influx of patients and the growing demand for beds, financial and material resources, thereby highlighting its flexibility and central role in the healthcare system.

Inhibition of the Arp2/3 complex represses human lung myofibroblast differentiation and attenuates bleomycin-induced pulmonary fibrosis.

Background And Purpose: The Arp2/3 multiprotein complex regulates branched polymerisation of the actin cytoskeleton and may contribute to collagen synthesis and fibrogenesis in the lung.

Experimental Approach: Expression of Arp2/3 components was assessed in human lung fibroblasts and in the bleomycin-induced pulmonary fibrosis model in mice. The Arp2/3 complex was repressed with the allosteric inhibitor CK666 and with interfering RNAs targeting the ARP2, ARP3 and ARPC2 subunits (siARP2, siARP3 and siARPC2) in CCD-16Lu human lung fibroblasts in vitro.

Noninvasive ventilation vs. high-flow nasal cannula oxygen for preoxygenation before intubation in patients with obesity: a post hoc analysis of a randomized controlled trial.

Background: Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity.

Methods: Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO/FiO < 300 mm Hg).

Pharmacokinetics of colistin after nebulization or intravenous administration of colistin methanesulphonate (Colimycin®) to cystic fibrosis patients.

Objectives: Colistin, administered as the prodrug colistin methanesulphonate (CMS), is an antibiotic frequently administered as aerosol in cystic fibrosis (CF) patient. Our aim was to assess the plasma PK of colistin in CF patients treated with CMS administered intravenously or as aerosol and to compare these results with those previously reported in healthy volunteers.

Methods: Six CF patients were included, CMS and colistin concentrations were measured in plasma, urine and sputum.

Nasal High-Flow Nebulization for Lung Drug Delivery: Theoretical, Experimental, and Clinical Application.

The use of nasal high-flow (NHF) therapy is rapidly spreading across acute care facilities. This raises the question of optimal delivery of inhaled medication to patients undergoing this noninvasive ventilatory support consisting in delivering heated and humidified high gas flow rates through nasal cannulas. In this article, we review experimental and clinical work evaluating the delivery of inhaled medication within the NHF circuit to target the lung without interrupting the ventilatory support.

Non-invasive ventilation versus high-flow nasal cannula oxygen therapy with apnoeic oxygenation for preoxygenation before intubation of patients with acute hypoxaemic respiratory failure: a randomised, multicentre, open-label trial.

Background: Non-invasive ventilation has never been compared with high-flow oxygen to determine whether it reduces the risk of severe hypoxaemia during intubation. We aimed to determine if preoxygenation with non-invasive ventilation was more efficient than high-flow oxygen in reducing the risk of severe hypoxaemia during intubation.

Methods: The FLORALI-2 multicentre, open-label trial was done in 28 intensive care units in France.

Impact of the TAP-like transporter in antigen presentation and phagosome maturation.

Cross-presentation is thought to require transport of proteasome-generated peptides by the TAP transporters into MHC class I loading compartments for most antigens. However, a proteasome-dependent but TAP-independent pathway has also been described. Depletion of the pool of recycling cell surface MHC class I molecules available for loading with cross-presented peptides might partly or largely account for the critical role of TAP in cross-presentation of phagocytosed antigens.

[The pentoxifylline, a corticosteroid sparing in the treatment of sarcoidosis: A case report].

Introduction: The pentoxifylline seems to have some effects on immune cells by inhibiting tumor necrosis factor alpha (TNFα). Its role as a sparing corticosteroids in the treatment of sarcoidosis remains to be defined.

Clinical Case: We present the case of a patient with sarcoidosis corticodependent despite the use of azathioprine.

Formyl Peptide Receptor 2 Plays a Deleterious Role During Influenza A Virus Infections.

Background: The pathogenesis of influenza A virus (IAV) infections is a multifactorial process that includes the replication capacity of the virus and a harmful inflammatory response to infection. Formyl peptide receptor 2 (FPR2) emerges as a central receptor in inflammatory processes controlling resolution of acute inflammation. Its role in virus pathogenesis has not been investigated yet.

Characterization of different vitamin E carriers intended for pulmonary drug delivery.

The targeted release of drugs intended for pulmonary delivery is a research field which has been so far rather unexploited but is currently becoming increasingly attractive. Liquid dispersions encapsulating vitamin E (liposomes, micelles, nano-emulsion, and solid lipid particles) were prepared using various methods based on membrane contactor. The dispersions were nebulized and aerodynamic characteristics of the generated aerosols were assessed using two different methods: laser light scattering and cascade impaction.

Assessing sinus aerosol deposition: benefits of SPECT-CT imaging.

Purpose: Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders.

Comparison of numerical simulations to experiments for atomization in a jet nebulizer.

The development of jet nebulizers for medical purposes is an important challenge of aerosol therapy. The performance of a nebulizer is characterized by its output rate of droplets with a diameter under 5 µm. However the optimization of this parameter through experiments has reached a plateau.

Relevance of the mouse model as a therapeutic approach for neutrophil proteinase 3-associated human diseases.

Proteinase 3 (PR3) is one of the four elastase-related serine proteinases stored in the azurophilic granules of neutrophils. Although it participates in the pro- and anti-inflammatory responses to infection and inflammation it also retains specific functions that make it different from neutrophil elastase in spite of their close structural resemblance. PR3 is involved in the immune response to infection and is the major autoantigen in granulomatosis with polyangiitis (GPA, formerly Wegener disease), an autoimmune systemic vasculitis with granulomas.

Selective inhibitors of human neutrophil proteinase 3.

Human neutrophil proteinase 3 (PR3) and elastase (HNE) are homologous serine proteinases involved in the proteolytic events associated with inflammation and infection. Their close structural and functional resemblance makes it difficult to understand their respective biological functions. Thus, all natural inhibitors of PR3 identified to date preferentially target HNE, and only recently have inhibitors that target PR3 selectively been described.