Association between driving pressure, systemic inflammation and non-pulmonary organ dysfunction in patients with acute respiratory distress syndrome, a prospective pathophysiological study.

Background: Driving pressure is thought to determine the effect of low tidal ventilation on survival in patients with acute respiratory distress syndrome. The leading cause of mortality in these patients is non-pulmonary multiorgan dysfunction, which is believed to worsen due to the biological response to mechanical ventilation (biotrauma). Therefore, we aimed to analyze the association between driving pressure, biotrauma, and non-pulmonary multiorgan dysfunction.

Healing the Cornea: Exploring the Therapeutic Solutions Offered by MSCs and MSC-derived EVs.

Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs).

Tumor-associated mesenchymal stromal cells modulate macrophage phagocytosis in stromal-rich colorectal cancer via PD-1 signaling.

CMS4 colorectal cancer (CRC), based on the consensus molecular subtype (CMS), stratifies patients with the poorest disease-free survival rates. It is characterized by a strong mesenchymal stromal cell (MSC) signature, wound healing-like inflammation and therapy resistance. We utilized 2D and 3D , and models to assess the impact of inflammation and stromal cells on immunosuppression in CMS4 CRC.

Immunomodulatory potential of cytokine-licensed human bone marrow-derived mesenchymal stromal cells correlates with potency marker expression profile.

Cytokine(s) pre-activation/licensing is an effective way to enhance the immunomodulatory potency of mesenchymal stromal cells (MSCs). Currently, IFN-γ licensing received the most attention in comparison with other cytokines. After licensing human bone marrow-derived MSCs with pro-/anti-inflammatory cytokines IFN-γ, IL-1β, TNF-α, TGF-β1 alone or in combination, the in vitro immunomodulatory potency of these MSCs was studied by incubating with allogeneic T cells and macrophage-like THP-1 cells.

Survival and maturation of human induced pluripotent stem cell-derived dopaminergic progenitors in the parkinsonian rat brain is enhanced by transplantation in a neurotrophin-enriched hydrogel.

Although human induced pluripotent stem cell (iPSC)-derived cell replacement for Parkinson's disease has considerable reparative potential, its full therapeutic benefit is limited by poor graft survival and dopaminergic maturation. Injectable biomaterial scaffolds, such as collagen hydrogels, have the potential to address these issues via a plethora of supportive benefits including acting as a structural scaffold for cell adherence, shielding from the host immune response and providing a reservoir of neurotrophic factors to aid survival and differentiation. Thus, the aim of this study was to determine if a neurotrophin-enriched collagen hydrogel could improve the survival and maturation of iPSC-derived dopaminergic progenitors (iPSC-DAPs) after transplantation into the rat parkinsonian brain.

Cell-based Therapies for Acute Respiratory Distress Syndrome: Where Are We Now?

There is considerable interest in the potential for cell-based therapies, particularly mesenchymal stromal cells (MSCs) and their products, as a therapy for acute respiratory distress syndrome (ARDS). MSCs exert effects via diverse mechanisms including reducing excessive inflammation by modulating neutrophil, macrophage and T-cell function, decreasing pulmonary permeability and lung edema, and promoting tissue repair. Clinical studies indicate that MSCs are safe and well tolerated, with promising therapeutic benefits in specific clinical settings, leading to regulatory approvals of MSCs for specific indications in some countries.

Immunomodulatory function of licensed human bone marrow mesenchymal stromal cell-derived apoptotic bodies.

Background: Mesenchymal stromal cells (MSCs) show great potential for immunomodulatory and anti-inflammatory treatments. Clinical trials have been performed for the treatment of Type 1 diabetes, graft-versus-host disease and organ transplantation, which offer a promise of MSCs as an immunomodulatory therapy. Nevertheless, their unstable efficacy and immunogenicity concerns present challenges to clinical translation.

Delayed MSC therapy enhances resolution of organized pneumonia induced by antibiotic resistant infection.

Introduction: Mesenchymal stromal cells (MSC) are a promising therapeutic for pneumonia-induced sepsis. Here we sought to determine the efficacy of delayed administration of naïve and activated bone marrow (BM), adipose (AD), and umbilical cord (UC) derived MSCs in organized antibiotic resistant pneumosepsis.

Methods: Human BM-, AD-, and UC-MSCs were isolated and expanded and used either in the naïve state or following cytokine pre-activation.

Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes.

Objectives: To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes.

Design: Evaluation and in vitro validation study SETTING: Ventilator shortage during the SARS-CoV-2 pandemic.

Participants: The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals.

Differential Effects of Cytokine Versus Hypoxic Preconditioning of Human Mesenchymal Stromal Cells in Pulmonary Sepsis Induced by Antimicrobial-Resistant .

: Pulmonary sepsis is a leading cause of hospital mortality, and sepses arising from antimicrobial-resistant (AMR) bacterial strains are particularly difficult to treat. Here we investigated the potential of mesenchymal stromal cells (MSCs) to combat established pneumosepsis and further evaluated MSC preconditioning and pre-activation methods. : The potential for naïve and preconditioned MSCs to enhance wound healing, reduce inflammation, preserve metabolic activity, and enhance bacterial killing was assessed in vitro.

Multiple Dosing and Preactivation of Mesenchymal Stromal Cells Enhance Efficacy in Established Pneumonia Induced by Antimicrobial-Resistant in Rodents.

Antimicrobial-resistant (AMR) bacteria, such as species, are an increasingly common cause of hospital-acquired pneumonia, resulting in high mortality and morbidity. Harnessing the host immune response to AMR bacterial infection using mesenchymal stem cells (MSCs) is a promising approach to bypass bacterial AMR mechanisms. The administration of single doses of naïve MSCs to ARDS clinical trial patient cohorts has been shown to be safe, although efficacy is unclear.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148).

A new multiplex SARS-CoV-2 antigen microarray showed correlation of IgG, IgA, and IgM antibodies from patients with COVID-19 disease severity and maintenance of relative IgA and IgM antigen binding over time.

Zoonotic spillover of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to humans in December 2019 caused the coronavirus disease 2019 (COVID-19) pandemic. Serological monitoring is critical for detailed understanding of individual immune responses to infection and protection to guide clinical therapeutic and vaccine strategies. We developed a high throughput multiplexed SARS-CoV-2 antigen microarray incorporating spike (S) and nucleocapsid protein (NP) and fragments expressed in various hosts which allowed simultaneous assessment of serum IgG, IgA, and IgM responses.

Chronic Kidney Disease Is Characterized by Expansion of a Distinct Proinflammatory Intermediate Monocyte Subtype and by Increased Monocyte Adhesion to Endothelial Cells.

Significance Statement: CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function.

The development and preliminary evaluation of a clinician e-learning training platform for a neonatal sepsis risk monitor for use in ICU settings.

Background: Training clinicians on the use of hospital-based patient monitoring systems (PMS) is vital to mitigate the risk of use errors and of frustration using these devices, especially when used in ICU settings. PMS training is typically delivered through face-to-face training sessions in the hospital. However, it is not always feasible to deliver training in this format to all clinical staff given some constraints (e.

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study.

Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation.

Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries.

Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study.

Background: Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.

Methods: Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied.

Feasibility of pair-housing of rats after cranial implant surgery.

Rat models employing cranial implants are increasingly employed to facilitate neural stimulation and recording in freely moving animals. Due to possible damage to wound, implant or attached devices, rats with cranial implants are traditionally housed singly, and little information is available on group- or pair-housing. Here we describe a protocol for pair-housing rats following cranial implant surgery and describe our experience with pair-housing during post-surgical recovery and up to 16 weeks following surgery.

Monitoring Lung Injury Severity and Ventilation Intensity during Mechanical Ventilation.

Acute respiratory distress syndrome (ARDS) is a severe form of respiratory failure burden by high hospital mortality. No specific pharmacologic treatment is currently available and its ventilatory management is a key strategy to allow reparative and regenerative lung tissue processes. Unfortunately, a poor management of mechanical ventilation can induce ventilation induced lung injury (VILI) caused by physical and biological forces which are at play.

Stimulation-induced changes at the electrode-tissue interface and their influence on deep brain stimulation.

. During deep brain stimulation (DBS) the electrode-tissue interface (ETI) forms a critical path between device and brain tissue. Although changes in the electrical double layer (EDL) and glial scar can impact stimulation efficacy, the effects of chronic DBS on the ETI have not yet been established.