Recent Advances and Future Directions in Extracorporeal Carbon Dioxide Removal.

Extracorporeal carbon dioxide removal (ECCOR) is an emerging technique designed to reduce carbon dioxide (CO) levels in venous blood while enabling lung-protective ventilation or alleviating the work of breathing. Unlike high-flow extracorporeal membrane oxygenation (ECMO), ECCOR operates at lower blood flows (0.4-1.

Artificial Intelligence to Close the Gap between Pharmacokinetic/Pharmacodynamic Targets and Clinical Outcomes in Critically Ill Patients: A Narrative Review on Beta Lactams.

Antimicrobial dosing can be a complex challenge. Although a solid rationale exists for a link between antibiotic exposure and outcome, conflicting data suggest a poor correlation between pharmacokinetic/pharmacodynamic targets and infection control. Different reasons may lead to this discrepancy: poor tissue penetration by β-lactams due to inflammation and inadequate tissue perfusion; different bacterial response to antibiotics and biofilms; heterogeneity of the host's immune response and drug metabolism; bacterial tolerance and acquisition of resistance during therapy.

Monitoring of the Forgotten Immune System during Critical Illness-A Narrative Review.

Immune organ failure is frequent in critical illness independent of its cause and has been acknowledged for a long time. Most patients admitted to the ICU, whether featuring infection, trauma, or other tissue injury, have high levels of alarmins expression in tissues or systemically which then activate innate and adaptive responses. Although necessary, this response is frequently maladaptive and leads to organ dysfunction.

β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity.

Antimicrobial prescription in critically ill patients represents a complex challenge due to the difficult balance between infection treatment and toxicity prevention. Underexposure to antibiotics and therapeutic failure or, conversely, drug overexposure and toxicity may both contribute to a worse prognosis. Moreover, changes in organ perfusion and dysfunction often lead to unpredictable pharmacokinetics.

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study.

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform.

Acute HIV-1 and SARS-CoV-2 Infections Share Slan+ Monocyte Depletion-Evidence from an Hyperacute HIV-1 Case Report.

Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear.

SARS-CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10.

Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection.

Severe COVID-19 Recovery Is Associated with Timely Acquisition of a Myeloid Cell Immune-Regulatory Phenotype.

After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions.

Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease.

Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients' follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects.

Human naïve regulatory T-cells feature high steady-state turnover and are maintained by IL-7.

Naïve FoxP3-expressing regulatory T-cells (Tregs) are essential to control immune responses via continuous replenishment of the activated-Treg pool with thymus-committed suppressor cells. The mechanisms underlying naïve-Treg maintenance throughout life in face of the age-associated thymic involution remain unclear. We found that in adults thymectomized early in infancy the naïve-Treg pool is remarkably well preserved, in contrast to conventional naïve CD4 T-cells.

Enteric mucosa integrity in the presence of a preserved innate interleukin 22 compartment in HIV type 1-treated individuals.

Background: Interleukin 22 (IL-22) is emerging as a key cytokine for gut epithelial homeostasis and mucosal repair. Gut disruption is a hallmark of human immunodeficiency virus (HIV) infection. Here, we investigated IL-22 production and gut mucosal integrity in HIV type 1 (HIV-1)-infected individuals receiving long-term antiretroviral therapy (ART).

Types of clinical studies. II. Cohort studies.

Cohort studies include groups of patients that are followed over time to determine the incidence or natural history of a disease, together with the risk factors for specific outcomes. These studies can be used to determine disease characteristics as well as the causal relationship between exposure and disease. They are, however, very expensive, because they need large patient samples.

Studies of harm. Clinical applications.

When a clinician institutes a therapy, he/she has to consider, besides its efficacy, the harm a substance that is foreign to the body may cause. Nowadays, with the number of drugs available, more and more iatrogenic events are occurring, to the extent that the term 'iatroepidemic' has been coined to describe the phenomenon. Harm can be assessed by experimental studies, but this design raises ethical as well as financial issues, so the best evidence is gathered from observational data, mainly case-control and cohort studies.