Enhancing sepsis biomarker development: key considerations from public and private perspectives.

Implementation of biomarkers in sepsis and septic shock in emergency situations, remains highly challenging. This viewpoint arose from a public-private 3-day workshop aiming to facilitate the transition of sepsis biomarkers into clinical practice. The authors consist of international academic researchers and clinician-scientists and industry experts who gathered (i) to identify current obstacles impeding biomarker research in sepsis, (ii) to outline the important milestones of the critical path of biomarker development and (iii) to discuss novel avenues in biomarker discovery and implementation.

Whole blood no-lyse no-wash micromethod for the quantitative measurement of monocyte HLA-DR.

Background: Monocyte (m)HLA-DR expression appears to be a potent marker of immunosuppression in critically ill patients. The persistence of low mHLA-DR expression is associated with an increased risk of nosocomial infections and mortality. To adapt this measurement to pediatric requirements and provide extensive 24/7 access, we have developed a whole blood no-lyse no-wash micromethod (MM) and compared it with the standardized method (SM).

Case Report: Intercurrent infections in COVID-19-induced sustained immunodepression: is interferon gamma a suitable drug?

Acute immuno-depression syndrome (AIDs) had been observed in many life-threatening conditions leading to the Intensive Care Unit. and is associated with recurrent secondary infections. We report one COVID-19 patient with a severe ARDS, demonstrating acute immunodepression syndrome lasting for several weeks.

Intensive Care Unit activity in France from the national database between 2013 and 2019: More critically ill patients, shorter stay and lower mortality rate.

Background: Knowledge of the occurrence and outcome of admissions to Intensive Care Units (ICU) over time is important to inform healthcare services planning. This observational study aims at describing the activity of French ICUs between 2013 and 2019.

Methods: Patient admission characteristics, organ dysfunction scores, therapies, ICU and hospital lengths of stay and case fatality were collected from the French National Hospital Database (population-based cohort).

CIITA promoter polymorphism impairs monocytes HLA-DR expression in patients with septic shock.

Low monocyte (m)HLA-DR expression is associated with mortality in sepsis. G-286A∗rs3087456 polymorphism in promoter III of HLA class II transactivator (), the master regulator of HLA, has been associated with autoimmune diseases but its role in sepsis has never been demonstrated. In 203 patients in septic shock, GG genotype was associated with 28-day mortality and mHLA-DR remained low whereas it increased in patients with AA or AG genotype.

Renaissance of glucocorticoids in critical care in the era of COVID-19: ten urging questions.

The 40-year-old experience with glucocorticosteroids (GCs) in the context of severe infections is complex and troublesome. Recently, however, a clear indication for GCs in severe COVID-19 has been established. This may constitute a harbinger of a wider use of GCs in critical illnesses.

Interferon gamma as an immune modulating adjunct therapy for invasive mucormycosis after severe burn - A case report.

Background: Mucormycosis is a deadly fungal infection that mainly affects severely immunocompromised patients. We report herein the case of a previously immunocompetent adult woman who developed invasive cutaneous mucormycosis after severe burn injuries. Interferon-gamma (IFN-γ) treatment was added after failure of conventional treatment and confirmation of a sustained profound immunodepression.

Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections.

Introduction: The reports of an early and profound acquired immunodepression syndrome (AIDs) in ICU patients had gained sufficient credence to modify the paradigm of acute inflammation. However, despite several articles published on AIDs and its assessment by monocytic HLA-DR monitoring, several missing informations remained: 1-Which patients' are more prone to benefit from mHLA-DR measurement, 2-Is the nadir or the duration of the low mHLA-DR expression the main parameter to consider? 3-What are the compared performances of leukocytes' count analyses (lymphocyte, monocyte).

Material And Method: We conducted an observational study in a surgical ICU of a French tertiary hospital.

Case Report: Interferon- γ Rescues Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) Function in a COVID-19 Patient With ARDS and Superinfection With Multiple MDR 4MRGN Bacterial Strains.

Background: CD14+ monocytes present antigens to adaptive immune cells monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy.

Endotoxin Mass Concentration in Plasma Is Associated With Mortality in a Multicentric Cohort of Peritonitis-Induced Shock.

To investigate the association of plasma LPS mass with mortality and inflammation in patients with peritonitis-induced septic shock (SS). Longitudinal endotoxin and inflammatory parameters in a multicentric cohort of SS. Protocolized post-operative parameters of 187 SS patients collected at T1 (12 h max post-surgery) and T4 (24 h after T1).

Does the definition of fluid responsiveness affect passive leg raising reliability? A methodological ancillary analysis from a multicentric study.

Background: Fluid challenge (FC) is often adopted as gold standard used to assess the reliability of passive leg raising (PLR) in predicting fluid responsiveness in the intensive care unit (ICU). This study aimed to address the impact of the different definitions and timings used to assess FC response on PLR reliability.

Methods: Ancillary study from a data set of a multicentric study in 85 ICU patient with acute circulatory failure who received a FC (500 mL of crystalloids in 10 minutes) within the first 48h of ICU admission, preceded by PLR in 30 patients.

Temporary application of lower body positive pressure improves intracranial velocities in symptomatic acute carotid occlusion or tight stenosis: A pilot study.

Background: Patients with isolated cervical carotid artery occlusion not eligible to recanalization therapies but with compromised intracranial hemodynamics may be at risk of further clinical events. Apart from lying flat until spontaneous recanalization or adjustment of the collateral circulation hopefully occurs, no specific treatment is currently implemented. Improving collateral flow is an attractive option in this setting.

Current use of inotropes in circulatory shock.

Background: Treatment decisions on critically ill patients with circulatory shock lack consensus. In an international survey, we aimed to evaluate the indications, current practice, and therapeutic goals of inotrope therapy in the treatment of patients with circulatory shock.

Methods: From November 2016 to April 2017, an anonymous web-based survey on the use of cardiovascular drugs was accessible to members of the European Society of Intensive Care Medicine (ESICM).

Deep sedation vs femoral block anesthesia: beat-by-beat hemodynamic impact on TAVI procedure.

Background: In spite of the increased use of Trans-catheter Aortic Valve Implantation (TAVI) due to the better patient selection, well-trained operators and improved technology, the choice of the best anesthesia regimen remains an open question. In particular, it remains to be clarified whether deep sedation (DS) in spontaneous breathing or femoral local anesthesia (LA) is best.

Objective: This study compared the hemodynamic variations determined by deep sedation (DS) with spontaneous breathing and local femoral anesthesia (LA) in 2 groups of patients submitted to TAVI with two different kinds of anesthesia, using a beat-by-beat pulse contour method (MostCare).

A Longitudinal Study of Immune Cells in Severe COVID-19 Patients.

Unlabelled: Little is known about the time-dependent immune responses in severe COVID-19. Data of 15 consecutive patients were sequentially recorded from intensive care unit admission. Lymphocyte subsets and total monocyte and subsets counts were monitored as well as the expression of HLA-DR.

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome.

Background: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients.

Methods: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS.

Multivariable haemodynamic approach to predict the fluid challenge response: A multicentre cohort study.

Background: Beat-to-beat stroke volume (SV) results from the interplay between left ventricular function and arterial load. Fluid challenge induces time-dependent responses in cardiac performance and peripheral vascular and capillary characteristics.

Objective: To assess whether analysis of the determinants of the haemodynamic response during fluid challenge can predict the final response at 10 and 30 min.