Considering local immunity for innovative immunomodulatory approaches: pulmonary sepsis as a use case.

Owing to faster identification of sepsis and improvement of patient management, most septic patients now survive the early phase of sepsis. Therefore, one of the major challenges in sepsis management today is to identify those patients at risk and propose effective personalized therapy. The complexity of the mechanisms involved in the septic immune response and its dysregulation is reflected in the diversity of immune profiles among sepsis patients.

Epidemiology and Impact of Staff Training in Controlling Complications Related to Central Venous Catheters in 4 Intensive Care Units in a French University Hospital: Protocol of a Prospective, Quasi-Experimental, Before-After Study.

Background: Central venous catheters (CVCs) are essential tools in the management of critically ill patients in intensive care units (ICUs). However, their use is associated with several preventable complications, including central line-associated bloodstream infections (CLABSIs), catheter-related thrombosis, and mechanical events (eg, occlusion and rupture). Despite the availability of evidence-based guidelines from the French Society of Hospital Hygiene for CVC insertion and maintenance, adherence variability persists across health care settings, contributing to prolonged hospitalization, increased morbidity and mortality, and even increased health care costs.

Incidence of nosocomial pneumonia in two intensive care units of a French University Hospital from 2016 to 2022 in the era of COVID-19 pandemic.

Background: Hospital-Acquired Pneumonia (HAP) are common in intensive care units (ICUs). The COVID-19 pandemic led to a global increase in healthcare-associated infections (HAI) among ICU patients. The aim of this study was to evaluate the trends in HAP incidence over a seven-year period of surveillance in two ICUs at a French University Hospital, and to assess the impact of COVID-19 (as well as the associated bacterial ecology).

The carbon footprint of general anaesthesia in adult patients: a multicentre observational comparison of intravenous and inhalation anaesthetic strategies in 35,242 procedures.

Background: General anaesthesia is a significant contributor to healthcare-related greenhouse gas (GHG) emissions. Previous studies have compared non-optimised anaesthesia strategies (desflurane, nitrous oxide, or both) to evaluate the impact of green initiatives on reducing the carbon footprint of anaesthesia. However, modern halogenated anaesthesia techniques, including low fresh gas flow and target-controlled inhalation anaesthesia (TCIA), offer potentially more environmentally friendly alternatives.

PD-L1 plasma cells suppress T lymphocyte responses in patients with sepsis and mouse sepsis models.

Sepsis, a leading cause of death in intensive care units, is associated with immune alterations that increase the patients' risk of secondary infections and mortality, so better understandings of the pathophysiology of sepsis-induced immunosuppression is essential for the development of therapeutic strategies. In a murine model of sepsis that recapitulates immune alterations observed in patients, here we demonstrate that PD-L1CD44B220CD138IgM regulatory plasma cells are induced in spleen and regulate ex vivo proliferation and IFNɣ secretion induced by stimulation of T splenocytes. This effect is mediated both by cell-cell contact through increased PD-L1 expression on plasma cells and by production of a soluble factor.

An Overview of Isavuconazole Clinical Use: A Multicentre Analysis of Indications, Exposure and Hepatic Safety.

Background: Isavuconazole is a recent broad-spectrum triazole indicated for the treatment of invasive aspergillosis and mucormycosis when amphotericin B is inappropriate. However, limited information exists on its clinical use.

Objective: We set up a retrospective multicentre study to describe the clinical practice of isavuconazole including indications, exposure, and hepatic safety.

An international observational study validating gene-expression sepsis immune subgroups.

Background: Sepsis gene-expression sub-phenotypes with prognostic and theranostic potential have been discovered. These have been identified retrospectively and have not been translated to methods that could be deployed at the bedside. We aimed to identify subgroups of septic patients at high-risk of poor outcome, using a rapid, multiplex RNA-based test.

Postoperative lymphopaenia as a risk factor for postoperative infections in cancer surgery: A prospective multicentre cohort study (the EVALYMPH study).

Background: Stress due to surgical trauma decreases postoperative lymphocyte counts (LCs), potentially favouring the occurrence of postoperative infections (PIs).

Objectives: We aimed to determine whether postoperative lymphopaenia following thoracic or gastrointestinal cancer surgery is an independent risk factor for PIs and to identify modifiable factors related to anaesthesia and surgical procedures that might affect its occurrence.

Study Design: The EVALYMPH study was a prospective, multicentre cohort study with a 30-day patient follow-up.

Reverse-transcriptase real-time PCR in the diagnostic strategy for invasive infections caused by .

The aim was to develop an RT-qPCR targeting and compare its performance to that of qPCR for the diagnosis of invasive aspergillosis (IA). Samples from patients of the Lyon University hospitals for whom a suspicion of IA led to the realization of an qPCR molecular diagnostic test over a 2-year period were included. The patients were classified according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC-MSGERC) criteria for suspected IA; RT-qPCR and qPCR assays were performed on all included samples.

Shadows and lights in sepsis immunotherapy.

Introduction: Sepsis remains a major global public health challenge. The host's response in sepsis involves both an exaggerated inflammatory reaction and immunosuppressive mechanisms. A better understanding of this response has shed light on the failure of anti-inflammatory therapies administered under the 'one size fits all' approach during the last decades.

DETECTION AND QUANTIFICATION OF MICROCIRCULATORY DYSFUNCTION IN SEVERE COVID-19 NOT REQUIRING MECHANICAL VENTILATION: A THREE-ARM COHORT STUDY.

Aim: To identify and describe microcirculatory dysfunction (MD) in severe COVID-19 cases. Methods: This prospective, cohort study evaluated microvascular function in COVID-19 patients with acute respiratory failure not requiring mechanical ventilation and compared it with that of non-COVID-19 intensive care unit (ICU)-matched controls. A validation cohort included healthy, comorbidity-free patients.

Phage Therapy in a Burn Patient Colonized with Extensively Drug-Resistant Responsible for Relapsing Ventilator-Associated Pneumonia and Bacteriemia.

is one of the main causes of healthcare-associated infection in Europe that increases patient morbidity and mortality. Multi-resistant pathogens are a major public health issue in burn centers. Mortality increases when the initial antibiotic treatment is inappropriate, especially if the patient is infected with strains that are resistant to many antibiotics.

Immune profiling of critically ill patients with acute kidney injury during the first week after various types of injuries: the REALAKI study.

Background: Acute kidney injury (AKI) is common in hospitalized patients and results in significant morbidity and mortality. The objective of the study was to explore the systemic immune response of intensive care unit patients presenting with AKI, especially the association between immune profiles and persistent AKI during the first week after admission following various types of injuries (sepsis, trauma, surgery, and burns).

Methods: REALAKI is an ancillary analysis of the REAnimation Low Immune Status Marker (REALISM) cohort study, in which 359 critically ill patients were enrolled in three different intensive care units.

Joint modeling of monocyte HLA-DR expression trajectories predicts 28-day mortality in severe SARS-CoV-2 patients.

The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients.

Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients.

Background: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented.

Use of Immune Profiling Panel to assess the immune response of septic patients for prediction of worsening as a composite endpoint.

Sepsis induces intense, dynamic and heterogeneous host response modulations. Despite improvement of patient management, the risk of mortality and healthcare-associated infections remains high. Treatments to counterbalance immune response are under evaluation, but effective biomarkers are still lacking to perform patient stratification.

Cefiderocol in Difficult-to-Treat Nf-GNB in ICU Settings.

Background: The efficacy and safety of cefiderocol in ICU patients with difficult-to-treat resistance (DTR) non-fermenting Gram-negative bacteria (Nf-GNB) are not as well-established. Consequently, we conducted a cohort study to compare Cefiderocol with the Best Available Therapy (BAT) in ICU patients.

Methods: We included adult patients from 9 different ICUs, including a burn ICU unit, from 2019 to 2023 treated with Cefiderocol for DTR Nf-GNB isolated from the blood or lungs.

Persistent NLRP3 inflammasome activation is associated with delayed immunosuppression in septic patients.

Sepsis triggers a complex response marked by the simultaneous presence of proinflammatory and immunosuppressive elements, disrupting the mechanisms intended to maintain homeostasis. While the NLRP3 inflammasome has been demonstrated to contribute to the inflammatory side, its connection with delayed sepsis-induced immunosuppression remains unexplored. The present objective was to concomitantly and prospectively assess NLRP3 activation (IL-1β, IL-18, and soluble receptors) and features of immune failure (IL-10, mHLA-DR, myeloid-derived suppressor cells) in septic patients.