Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation (the PROMIZING study): update to the statistical analysis plan for a randomized controlled trial.

Background: We previously published the protocol and statistical analysis plan for a randomized controlled trial of Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: the PROMIZING study in Trials ( https://doi.org/10.1186/s13063-023-07163-w ).

Proportional modes to hasten weaning.

Purpose Of Review: The purpose of this review is to examine the current state of the evidence, including several recent systematic reviews and meta-analyses, to determine if proportional modes of ventilation have the potential to hasten weaning from mechanical ventilation for adult critically ill patients, compared to pressure support ventilation (PSV), the current standard of care during the recovery and weaning phases of mechanical ventilation.

Recent Findings: Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) are two commercially available proportional modes that have been studied in randomized controlled trials (RCTs). Although several feasibility studies were not powered to detect differences in clinical outcomes, emerging evidence suggests that both PAV and NAVA may reduce duration of mechanical ventilation, intensive care unit (ICU) length of stay, and hospital mortality compared to PSV, as shown in some small, primarily single-centre studies.

Intensive care unit interventions to promote sleep and circadian biology in reducing incident delirium: a scoping review.

Rationale/objectives: Despite plausible pathophysiological mechanisms, research is needed to confirm the relationship between sleep, circadian rhythm and delirium in patients admitted to the intensive care unit (ICU). The objective of this review is to summarise existing studies promoting, in whole or in part, the normalisation of sleep and circadian biology and their impact on the incidence, prevalence, duration and/or severity of delirium in ICU.

Methods: A sensitive search of electronic databases and conference proceedings was completed in March 2023.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD.

Macrophages and neutrophils are necessary for ER stress-induced β cell loss.

Persistent endoplasmic reticulum (ER) stress induces islet inflammation and β cell loss. How islet inflammation contributes to β cell loss remains uncertain. We have reported previously that chronic overnutrition-induced ER stress in β cells causes Ripk3-mediated islet inflammation, macrophage recruitment, and a reduction of β cell numbers in a zebrafish model.

When donor T cells attack: The curious case of liver transplant-associated acute graft-versus-host-disease.

Graft versus host disease is a rare but deadly complication of solid organ transplant. Clinical features of graft-versus-host-disease are non-specific, which may lead to delayed diagnosis as more common conditions including infections or drug reactions are considered. We describe a 54-year-old male patient who underwent liver transplantation for alcohol use disorder-related cirrhosis and developed acute graft-versus-host disease.

Clinical characteristics, multiorgan dysfunction and outcomes of patients with COVID-19: a prospective case series.

Background: Characterizing the multiorgan manifestations and outcomes of patients hospitalized with COVID-19 will inform resource requirements to address the long-term burden of this disease. We conducted a descriptive analysis using prospectively collected data to describe the clinical characteristics and spectrum of organ dysfunction, and in-hospital and longer-term clinical outcomes of patients hospitalized with COVID-19 during the first wave of the pandemic at a Canadian centre.

Methods: We conducted a prospective case series involving adult patients (aged ≥ 18 yr) with COVID-19 admitted to 1 of 2 hospitals in London, Ontario, from Mar.

Liberation from Mechanical Ventilation: Established and New Insights.

A substantial proportion of critically ill patients require ventilator support with the majority requiring invasive mechanical ventilation. Timely and safe liberation from invasive mechanical ventilation is a critical aspect of patient care in the intensive care unit (ICU) and is a top research priority for patients and clinicians. In this article, we discuss how to (1) identify candidates for liberation from mechanical ventilation, (2) conduct spontaneous breathing trials (SBTs), and (3) optimize patients for liberation from mechanical ventilation.

The PROMIZING trial enrollment algorithm for early identification of patients ready for unassisted breathing.

Background: Liberating patients from mechanical ventilation (MV) requires a systematic approach. In the context of a clinical trial, we developed a simple algorithm to identify patients who tolerate assisted ventilation but still require ongoing MV to be randomized. We report on the use of this algorithm to screen potential trial participants for enrollment and subsequent randomization in the Proportional Assist Ventilation for Minimizing the Duration of MV (PROMIZING) study.

The physiological underpinnings of life-saving respiratory support.

Treatment of respiratory failure has improved dramatically since the polio epidemic in the 1950s with the use of invasive techniques for respiratory support: mechanical ventilation and extracorporeal respiratory support. However, respiratory support is only a supportive therapy, designed to "buy time" while the disease causing respiratory failure abates. It ensures viable gas exchange and prevents cardiorespiratory collapse in the context of excessive loads.

Effects of Arachidonic Acid and Its Metabolites on Functional Beta-Cell Mass.

Arachidonic acid (AA) is a polyunsaturated 20-carbon fatty acid present in phospholipids in the plasma membrane. The three primary pathways by which AA is metabolized are mediated by cyclooxygenase (COX) enzymes, lipoxygenase (LOX) enzymes, and cytochrome P450 (CYP) enzymes. These three pathways produce eicosanoids, lipid signaling molecules that play roles in biological processes such as inflammation, pain, and immune function.

Pharmacological modulation of prostaglandin E (PGE ) EP receptors improves cardiomyocyte function under hyperglycemic conditions.

Type 2 diabetes (T2D) affects >30 million Americans and nearly 70% of individuals with T2D will die from cardiovascular disease (CVD). Circulating levels of the inflammatory signaling lipid, prostaglandin E (PGE ), are elevated in the setting of obesity and T2D and are associated with decreased cardiac function. The EP3 and EP4 PGE receptors have opposing actions in several tissues, including the heart: overexpression of EP3 in cardiomyocytes impairs function, while EP4 overexpression improves function.

Glucose-6-phosphatase catalytic subunit 2 negatively regulates glucose oxidation and insulin secretion in pancreatic β-cells.

Elevated fasting blood glucose (FBG) is associated with increased risks of developing type 2 diabetes (T2D) and cardiovascular-associated mortality. G6PC2 is predominantly expressed in islets, encodes a glucose-6-phosphatase catalytic subunit that converts glucose-6-phosphate (G6P) to glucose, and has been linked with variations in FBG in genome-wide association studies. Deletion of G6pc2 in mice has been shown to lower FBG without affecting fasting plasma insulin levels in vivo.

Proportional-assist ventilation with load-adjustable gain factors for mechanical ventilation: a cost-utility analysis.

Background: Mechanical ventilation is an important component of patient critical care, but it adds expense to an already high-cost setting. This study evaluates the cost-utility of 2 modes of ventilation: proportional-assist ventilation with load-adjustable gain factors (PAV+ mode) versus pressure-support ventilation (PSV).

Methods: We adapted a published Markov model to the Canadian hospital-payer perspective with a 1-year time horizon.

Nonsynonymous single-nucleotide polymorphisms in the G6PC2 gene affect protein expression, enzyme activity, and fasting blood glucose.

G6PC2 encodes a glucose-6-phosphatase (G6Pase) catalytic subunit that modulates the sensitivity of insulin secretion to glucose and thereby regulates fasting blood glucose (FBG). A common single-nucleotide polymorphism (SNP) in G6PC2, rs560887 is an important determinant of human FBG variability. This SNP has a subtle effect on G6PC2 RNA splicing, which raises the question as to whether nonsynonymous SNPs with a major impact on G6PC2 stability or enzyme activity might have a broader disease/metabolic impact.

Pharmacological blockade of the EP3 prostaglandin E receptor in the setting of type 2 diabetes enhances β-cell proliferation and identity and relieves oxidative damage.

Objective: Type 2 diabetes is characterized by hyperglycemia and inflammation. Prostaglandin E, which signals through four G protein-coupled receptors (EP1-4), is a mediator of inflammation and is upregulated in diabetes. We have shown previously that EP3 receptor blockade promotes β-cell proliferation and survival in isolated mouse and human islets ex vivo.

Acute Hemorrhagic Encephalitis Related to COVID-19.

Purpose Of Review: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the most critical public health challenge in recent history. In this report, we present a case of suspected acute hemorrhagic encephalitis with bilateral intracranial hemorrhages associated with coronavirus disease 2019 (COVID-19) infection.

Recent Findings: A 48-year-old female COVID-19-positive patient developed acute changes in her neurologic status.

Knowledge translation tools to guide care of non-intubated patients with acute respiratory illness during the COVID-19 Pandemic.

Providing optimal care to patients with acute respiratory illness while preventing hospital transmission of COVID-19 is of paramount importance during the pandemic; the challenge lies in achieving both goals simultaneously. Controversy exists regarding the role of early intubation versus use of non-invasive respiratory support measures to avoid intubation. This review summarizes available evidence and provides a clinical decision algorithm with risk mitigation techniques to guide clinicians in care of the hypoxemic, non-intubated, patient during the COVID-19 pandemic.

Endothelial Injury and Glycocalyx Degradation in Critically Ill Coronavirus Disease 2019 Patients: Implications for Microvascular Platelet Aggregation.

Objectives: Coronavirus disease 2019 is caused by the novel severe acute respiratory syndrome coronavirus 2 virus. Patients admitted to the ICU suffer from microvascular thrombosis, which may contribute to mortality. Our aim was to profile plasma thrombotic factors and endothelial injury markers in critically ill coronavirus disease 2019 ICU patients to help understand their thrombotic mechanisms.

G6PC2 confers protection against hypoglycemia upon ketogenic diet feeding and prolonged fasting.

Objective: G6PC2 is predominantly expressed in pancreatic islet beta cells. G6PC2 hydrolyzes glucose-6-phosphate to glucose and inorganic phosphate, thereby creating a futile substrate cycle that opposes the action of glucokinase. This substrate cycle determines the sensitivity of glucose-stimulated insulin secretion to glucose and hence regulates fasting blood glucose (FBG) but not fasting plasma insulin (FPI) levels.

Pulmonary Functional MRI and CT in a Survivor of Bronchiolitis and Respiratory Failure Caused by e-Cigarette Use.

Although nearly 3,000 e-cigarette-related hospitalizations have been reported in North America, the long-term outcomes in these patients have not been described. We followed an 18-year-old boy who survived acute critical illness and respiratory failure related to 5 months of e-cigarette use. Chronic irreversible airflow obstruction and markedly abnormal Xe MRI ventilation heterogeneity was observed and persisted 8 months after hospital discharge, despite improvement in quality-of-life and chest CT findings.