Machine Learning Predicts Unplanned Care Escalations for Post-Anesthesia Care Unit Patients during the Perioperative Period: A Single-Center Retrospective Study.

Background:  Despite low mortality for elective procedures in the United States and developed countries, some patients have unexpected care escalations (UCE) following post-anesthesia care unit (PACU) discharge. Studies indicate patient risk factors for UCE, but determining which factors are most important is unclear. Machine learning (ML) can predict clinical events.

Tau and Aβ42 in lavage fluid of pneumonia patients are associated with end-organ dysfunction: A prospective exploratory study.

Background: Bacterial pneumonia and sepsis are both common causes of end-organ dysfunction, especially in immunocompromised and critically ill patients. Pre-clinical data demonstrate that bacterial pneumonia and sepsis elicit the production of cytotoxic tau and amyloids from pulmonary endothelial cells, which cause lung and brain injury in naïve animal subjects, independent of the primary infection. The contribution of infection-elicited cytotoxic tau and amyloids to end-organ dysfunction has not been examined in the clinical setting.

Sympathetic remodeling and altered angiotensin-converting enzyme 2 localization occur in patients with cardiac disease but are not exacerbated by severe COVID-19.

Purpose: Remodeling of sympathetic nerves and ACE2 has been implicated in cardiac pathology, and ACE2 also serves as a receptor for SARS-CoV-2. However, there is limited histological knowledge about the transmural distribution of sympathetic nerves and the cellular localization and distribution of ACE2 in human left ventricles from normal or diseased hearts. Goals of this study were to establish the normal pattern for these parameters and determine changes that occurred in decedents with cardiovascular disease alone compared to those with cardiac pathology and severe COVID-19.

Altered response to Toll-like receptor 4 activation in fibromyalgia: A low-dose, human experimental endotoxemia pilot study.

In this pilot study, a human intravenous injection of low-dose endotoxin (lipopolysaccharide, LPS) model was used to test if fibromyalgia is associated with altered immune responses to Toll-like receptor 4 (TLR4) activation. Eight women with moderately-severe fibromyalgia and eight healthy women were administered LPS at 0.1 ng/kg in session one and 0.

Lung endothelium, tau, and amyloids in health and disease.

Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes.

PFKFB3 Inhibits Fructose Metabolism in Pulmonary Microvascular Endothelial Cells.

Pulmonary microvascular endothelial cells contribute to the integrity of the lung gas exchange interface, and they are highly glycolytic. Although glucose and fructose represent discrete substrates available for glycolysis, pulmonary microvascular endothelial cells prefer glucose over fructose, and the mechanisms involved in this selection are unknown. 6-Phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) is an important glycolytic enzyme that drives glycolytic flux against negative feedback and links glycolytic and fructolytic pathways.

Massive Trauma and Resuscitation Strategies.

Massive trauma remains the leading cause of mortality among people aged younger than 45 years. In this review, we discuss the initial care and diagnosis of trauma patients followed by a comparison of resuscitation strategies. We discuss various strategies including use of whole blood and component therapy, examine viscoelastic techniques for management of coagulopathy, and consider the benefits and limitations of the resuscitation strategies and consider a series of questions that will be important for researchers to answer to provide the best and most cost-effective therapy for severely injured patients.

Sympathetic innervation of human and porcine spleens: implications for between species variation in function.

Background: The vagus nerve affects innate immune responses by activating spleen-projecting sympathetic neurons, which modulate leukocyte function. Recent basic and clinical research investigating vagus nerve stimulation to engage the cholinergic anti-inflammatory pathway (CAP) has shown promising therapeutic results for a variety of inflammatory diseases. Abundant sympathetic innervation occurs in rodent spleens, and use of these species has dominated mechanistic research investigating the CAP.

COVID-19 and Long-Term Outcomes: Lessons from Other Critical Care Illnesses and Potential Mechanisms.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that is currently causing a pandemic and has been termed coronavirus disease (COVID-19). The elderly or those with preexisting conditions like diabetes, hypertension, coronary heart disease, chronic obstructive pulmonary disease, cerebrovascular disease, or kidney dysfunction are more likely to develop severe cases when infected. Patients with COVID-19 admitted to the ICU have higher mortality than non-ICU patients.

ExoU Induces Lung Endothelial Cell Damage and Activates Pro-Inflammatory Caspase-1 during Infection.

The Gram-negative, opportunistic pathogen utilizes a type III secretion system to inject exoenzyme effectors into a target host cell. Of the four best-studied exoenzymes, ExoU causes rapid cell damage and death. ExoU is a phospholipase A (PLA) that hydrolyses host cell membranes, and strains expressing ExoU are associated with poor outcomes in critically ill patients with pneumonia.

Cytotoxic tau released from lung microvascular endothelial cells upon infection with Pseudomonas aeruginosa promotes neuronal tauopathy.

Patients who recover from nosocomial pneumonia oftentimes exhibit long-lasting cognitive impairment comparable with what is observed in Alzheimer's disease patients. We previously hypothesized that the lung endothelium contributes to infection-related neurocognitive dysfunction, because bacteria-exposed endothelial cells release a form(s) of cytotoxic tau that is sufficient to impair long-term potentiation in the hippocampus. However, the full-length lung and endothelial tau isoform(s) have yet to be resolved and it remains unclear whether the infection-induced endothelial cytotoxic tau triggers neuronal tau aggregation.

The Role of Virulence Factors in Cytoskeletal Dysregulation and Lung Barrier Dysfunction.

is an opportunistic pathogen that causes serious infections and hospital-acquired pneumonia in immunocompromised patients. accounts for up to 20% of all cases of hospital-acquired pneumonia, with an attributable mortality rate of ~30-40%. The poor clinical outcome of -induced pneumonia is ascribed to its ability to disrupt lung barrier integrity, leading to the development of lung edema and bacteremia.

Phosphodiesterase 4 mediates interleukin-8-induced heterologous desensitization of the β -adrenergic receptor.

Acute respiratory distress syndrome (ARDS) is a life-threatening illness characterized by decreased alveolar-capillary barrier function, pulmonary edema consisting of proteinaceous fluid, and inhibition of net alveolar fluid transport responsible for resolution of pulmonary edema. There is currently no pharmacotherapy that has proven useful to prevent or treat ARDS, and two trials using beta-agonist therapy to treat ARDS demonstrated no effect. Prior studies indicated that IL-8-induced heterologous desensitization of the beta2-adrenergic receptor (β -AR) led to decreased beta-agonist-induced mobilization of cyclic adenosine monophosphate (cAMP).

Pneumonia initiates a tauopathy.

Pneumonia causes short- and long-term cognitive dysfunction in a high proportion of patients, although the mechanism(s) responsible for this effect are unknown. Here, we tested the hypothesis that pneumonia-elicited cytotoxic amyloid and tau variants: (1) are present in the circulation during infection; (2) lead to impairment of long-term potentiation; and, (3) inhibit long-term potentiation dependent upon tau. Cytotoxic amyloid and tau species were recovered from the blood and the hippocampus following pneumonia, and they were present in the extracorporeal membrane oxygenation oxygenators of patients with pneumonia, especially in those who died.

Carbonic Anhydrase IX and Hypoxia Promote Rat Pulmonary Endothelial Cell Survival during Infection.

Low tidal volume ventilation protects the lung in mechanically ventilated patients. The impact of the accompanying permissive hypoxemia and hypercapnia on endothelial cell recovery from injury is poorly understood. CA (carbonic anhydrase) IX is expressed in pulmonary microvascular endothelial cells (PMVECs), where it contributes to CO and pH homeostasis, bioenergetics, and angiogenesis.

Estrogen Alleviates Sex-Dependent Differences in Lung Bacterial Clearance and Mortality Secondary to Bacterial Pneumonia after Traumatic Brain Injury.

Traumatic brain injury (TBI) is the leading cause of injury-related death and disability in patients under the age of 46 years. Survivors of the initial injury often endure systemic complications such as pulmonary infection, and is one of the most common causes of nosocomial pneumonia in intensive care units. Female patients are less likely to develop secondary pneumonia after TBI, and pre-clinical studies have revealed a salutary role for estrogen after trauma.

Role of angiotensin-converting enzyme 2 and pericytes in cardiac complications of COVID-19 infection.

The prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly reached pandemic proportions, and knowledge about this virus and coronavirus disease 2019 (COVID-19) has expanded rapidly. This review focuses primarily on mechanisms that contribute to acute cardiac injury and dysfunction, which are common in patients with severe disease. The etiology of cardiac injury is multifactorial, and the extent is likely enhanced by preexisting cardiovascular disease.

Exoenzyme Y Contributes to End-Organ Dysfunction Caused by Pneumonia in Critically Ill Patients: An Exploratory Study.

is an opportunistic pathogen that causes pneumonia in immunocompromised and intensive care unit (ICU) patients. During host infection, upregulates the type III secretion system (T3SS), which is used to intoxicate host cells with exoenzyme (Exo) virulence factors. Of the four known Exo virulence factors (U, S, T and Y), ExoU has been shown in prior studies to associate with high mortality rates.

Virulent Pseudomonas aeruginosa infection converts antimicrobial amyloids into cytotoxic prions.

Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host-pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa possessing a functional T3SS and effectors induced the production and release of cytotoxic amyloids from lung endothelium, including beta amyloid, and tau.

α-Tocopherol Attenuates the Severity of -induced Pneumonia.

is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The type III secretion system (T3SS) of mediates many of the adverse effects of infection with this pathogen, including increased lung permeability in a Toll-like receptor 4/RhoA/PAI-1 (plasminogen activator inhibitor-1)-dependent manner. α-Tocopherol has antiinflammatory properties that may make it a useful adjunct in treatment of this moribund infection.