Biological effects of corticosteroids on pneumococcal pneumonia in Mice-translational significance.

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model.

Neutrophil reduction attenuates the severity of lung injury in the early phase of pneumococcal pneumonia in mice.

Neutrophils are the first leukocytes to be recruited to sites of inflammation in response to chemotactic factors released by activated macrophages and pulmonary epithelial and endothelial cells in bacterial pneumonia, a common cause of acute respiratory distress syndrome (ARDS). Although neutrophilic inflammation facilitates the elimination of pathogens, neutrophils also may cause bystander tissue injury. Even though the presence of neutrophils in alveolar spaces is a key feature of acute lung injury and ARDS especially from pneumonia, their contribution to the pathogenesis of lung injury is uncertain.

Biological Effects of Corticosteroids on Pneumococcal Pneumonia in Mice and Humans.

Background: is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with .

A New Global Definition of Acute Respiratory Distress Syndrome.

Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would ) identify patients with the currently accepted conceptual framework for ARDS, ) facilitate rapid ARDS diagnosis for clinical care and research, ) be applicable in resource-limited settings, ) be useful for testing specific therapies, and ) be practical for communication to patients and caregivers.

Early plasma angiopoietin-2 is prognostic for ARDS and mortality among critically ill patients with sepsis.

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes.

Association of SARS-CoV-2 nucleocapsid viral antigen and the receptor for advanced glycation end products with development of severe disease in patients presenting to the emergency department with COVID-19.

Introduction: There remains a need to better identify patients at highest risk for developing severe Coronavirus Disease 2019 (COVID-19) as additional waves of the pandemic continue to impact hospital systems. We sought to characterize the association of receptor for advanced glycation end products (RAGE), SARS-CoV-2 nucleocapsid viral antigen, and a panel of thromboinflammatory biomarkers with development of severe disease in patients presenting to the emergency department with symptomatic COVID-19.

Methods: Blood samples were collected on arrival from 77 patients with symptomatic COVID-19, and plasma levels of thromboinflammatory biomarkers were measured.

Factors Associated With Total Discharge Opioid Prescription Morphine Milligram Equivalent Amounts Following Primary Anterior Cervical Spine Surgery.

Background: Opioid overuse is a substantial cause of morbidity and mortality in the United States, and orthopaedic surgeons are the third highest prescribers of opioids. Postoperative prescribing patterns vary widely, and there is a paucity of data evaluating patient and surgical factors associated with discharge opioid prescribing patterns after elective anterior cervical surgery (ACS). The purpose of this study was to evaluate the volume of postoperative opioids prescribed and factors associated with discharge opioid prescription volumes after elective ACS.

The prognostic value of early measures of the ventilatory ratio in the ARDS ROSE trial.

Background: The ventilatory ratio (VR, [minute ventilation × PaCO]/[predicted body weight × 100 × 37.5]) is associated with mortality in ARDS. The aims of this study were to test whether baseline disease severity or neuromuscular blockade (NMB) modified the relationship between VR and mortality.

Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19.

Background: Studies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes.

Opportunities for improved clinical trial designs in acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is a common critical illness syndrome with high morbidity and mortality. There are no proven pharmacological therapies for ARDS. The current definition of ARDS is based on shared clinical characteristics but does not capture the heterogeneity in clinical risk factors, imaging characteristics, physiology, timing of onset and trajectory, and biology of the syndrome.

Pulse oximetry for the diagnosis and management of acute respiratory distress syndrome.

The diagnosis of acute respiratory distress syndrome (ARDS) traditionally requires calculation of the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (PaO/FiO) using arterial blood, which can be costly and is not possible in many resource-limited settings. By contrast, pulse oximetry is continuously available, accurate, inexpensive, and non-invasive. Pulse oximetry-based indices, such as the ratio of pulse-oximetric oxygen saturation to FiO (SpO/FiO), have been validated in clinical studies for the diagnosis and risk stratification of patients with ARDS.

Impact of e-cigarette aerosol on primary human alveolar epithelial type 2 cells.

Electronic cigarettes (e-cigarettes) are designed to simulate combustible cigarette smoking and to aid in smoking cessation. Although the number of e-cigarette users has been increasing, the potential health impacts and biological effects of e-cigarettes are still not fully understood. Previous research has focused on the biological effects of e-cigarettes on lung cancer cell lines and distal airway epithelial cells; however, there have been few published studies on the effect of e-cigarettes on primary lung alveolar epithelial cells.

Ventilatory Ratio Is a Valuable Prognostic Indicator in an Observational Cohort of Patients With ARDS.

Background: How indices specific to respiratory compromise contribute to prognostication in patients with ARDS is not well characterized in general clinical populations. The primary objective of this study was to identify variables specific to respiratory failure that might add prognostic value to indicators of systemic illness severity in an observational cohort of subjects with ARDS.

Methods: Fifty subjects with ARDS were enrolled in a single-center, prospective, observational cohort.

Aerosolized vitamin E acetate causes oxidative injury in mice and in alveolar macrophages.

Although vitamin E acetate (VEA) is suspected to play a causal role in the development of electronic-cigarette, or vaping, product use-associated lung injury (EVALI), the underlying biological mechanisms of pulmonary injury are yet to be determined. In addition, no study has replicated the systemic inflammation observed in humans in a murine EVALI model, nor investigated potential additive toxicity of viral infection in the setting of exposure to vaping products. To identify the mechanisms driving VEA-related lung injury and test the hypothesis that viral infection causes additive lung injury in the presence of aerosolized VEA, we exposed mice to aerosolized VEA for extended times, followed by influenza infection in some experiments.

RAGE has potential pathogenetic and prognostic value in nonintubated hospitalized patients with COVID-19.

BackgroundThe value of the soluble receptor for advanced glycation end-products (sRAGE) as a biomarker in COVID-19 is not well understood. We tested the association between plasma sRAGE and illness severity, viral burden, and clinical outcomes in hospitalized patients with COVID-19 who were not mechanically ventilated.MethodsBaseline sRAGE was measured among participants enrolled in the ACTIV-3/TICO trial of bamlanivimab for hospitalized patients with COVID-19.

Gender, Racial, and Ethnic Differences in the Utilization of Cervical Disk Replacement for Cervical Radiculopathy.

Introduction: Cervical radiculopathy (CR) is commonly treated by spine surgeons, with surgical options including anterior cervical diskectomy and fusion (ACDF) and cervical disk replacement (CDR). CDR is a motion-sparing alternative to ACDF and was approved by the US FDA in 2007. CDR utilization has increased because evidence has emerged demonstrating its long-term efficacy.

Promises and challenges of personalized medicine to guide ARDS therapy.

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments.

Environmental Factors.

The acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality in the intensive care unit. Improving outcomes depends on not only evidence-based care once ARDS has already developed but also preventing ARDS incidence. Several environmental exposures have now been shown to increase the risk of ARDS and related adverse outcomes.

Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS.

BACKGROUNDWhether airspace biomarkers add value to plasma biomarkers in studying acute respiratory distress syndrome (ARDS) is not well understood. Mesenchymal stromal cells (MSCs) are an investigational therapy for ARDS, and airspace biomarkers may provide mechanistic evidence for MSCs' impact in patients with ARDS.METHODSWe carried out a nested cohort study within a phase 2a safety trial of treatment with allogeneic MSCs for moderate-to-severe ARDS.

Phenotypes and personalized medicine in the acute respiratory distress syndrome.

Although the acute respiratory distress syndrome (ARDS) is well defined by the development of acute hypoxemia, bilateral infiltrates and non-cardiogenic pulmonary edema, ARDS is heterogeneous in terms of clinical risk factors, physiology of lung injury, microbiology, and biology, potentially explaining why pharmacologic therapies have been mostly unsuccessful in treating ARDS. Identifying phenotypes of ARDS and integrating this information into patient selection for clinical trials may increase the chance for efficacy with new treatments. In this review, we focus on classifying ARDS by the associated clinical disorders, physiological data, and radiographic imaging.