Macrophages modulate skeletal muscle wasting and recovery in acute lung injury in mice.

Skeletal muscle dysfunction in critical illnesses leaves survivors weak and functionally impaired. Macrophages infiltrate muscles; however, their functional role is unclear. We aim to examine muscle leukocyte composition and the effect of macrophages on muscle mass and function in the murine acute lung injury (ALI)-associated skeletal muscle wasting model.

Phase I pilot safety and feasibility of a novel restraint device for critically ill patients requiring mechanical ventilation.

Background: Mechanically ventilated Intensive Care Unit (ICU) patients often require wrist restraints, contributing to immobility and agitation, over-sedation, and delirium. The ® ® (Healthy Design, LLC), a novel restraint alternative, may be safe and facilitate greater mobility than traditional restraints.

Objective: This National Institutes of Health Small Business Technology Transfer (STTR) Program Grant-funded single-site Phase I feasibility study evaluated ® safety and feasibility in anticipation of a multi-site Phase II randomized controlled trial (RCT).

Area deprivation index, a marker of socioeconomic disadvantage, may predict severity of COVID-19 in patients and which families may experience worse symptoms of PTSD, anxiety, and depression post-ICU.

Background: COVID-19 disproportionately impacted marginalized populations early in the pandemic. Families of patients admitted to the intensive care unit (ICU) experienced significant psychological effects. Little is known about whether individual and patient psychological outcomes after a loved ones stay in the ICU differs by socioeconomic status, as measured by the area deprivation index (ADI).

PD-L1 and PD-1 Are Associated with Clinical Outcomes and Alveolar Immune Cell Activation in Acute Respiratory Distress Syndrome.

The relationship between the PD-L1 (Programmed Death-Ligand 1)/PD-1 pathway, lung inflammation, and clinical outcomes in acute respiratory distress syndrome (ARDS) is poorly understood. We sought to determine whether PD-L1/PD-1 in the lung or blood is associated with ARDS and associated severity. We measured soluble PD-L1 (sPD-L1) in plasma and lower respiratory tract samples (ARDS1 [ = 59] and ARDS2 [ = 78]) or plasma samples alone (ARDS3 [ = 149]) collected from subjects with ARDS and tested for associations with mortality using multiple regression.

Evaluation of Three Cytomegalovirus IgG Lateral Flow Assays for Rapid Determination of CMV Serostatus.

Background: Cytomegalovirus (CMV) serostatus is a major determinant of CMV infection, disease risk, and transplant outcomes. Current clinical serology assays are limited by relatively slow turnaround time, design for batched testing, need for trained personnel, and/or specialized equipment. Rapid diagnostic assays in development have a role in emerging settings, such as critically ill patients, but have not been systematically evaluated.

How the Hospital Works: An Interdisciplinary, Systems-Based Practice Medical Student Elective.

Objectives: Although proficient systems-based practice is a foundational skill for physicians, how best to teach it has not been well established. An elective course for fourth-year medical students wherein participants had an immersive experience with multiple interprofessional staff was created and analyzed. The authors hypothesized that participating students and interprofessional staff would show gains in systems-based knowledge and interprofessional communication.

Research Bronchoscopies in Critically Ill Research Participants: An Official American Thoracic Society Workshop Report.

Bronchoscopy for research purposes is a valuable tool to understand lung-specific biology in human participants. Despite published reports and active research protocols using this procedure in critically ill patients, no recent document encapsulates the important safety considerations and downstream applications of this procedure in this setting. The objectives were to identify safe practices for patient selection and protection of hospital staff, provide recommendations for sample procurement to standardize studies, and give guidance on sample preparation for novel research technologies.

Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19.

Background: Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19.

Methods: Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC.

25-Hydroxycholesterol exacerbates vascular leak during acute lung injury.

Cholesterol-25-hydroxylase (CH25H), the biosynthetic enzyme for 25-hydroxycholesterol (25HC), is most highly expressed in the lung, but its role in lung biology is poorly defined. Recently, we reported that Ch25h is induced in monocyte-derived macrophages recruited to the airspace during resolution of lung inflammation and that 25HC promotes liver X receptor-dependent (LXR-dependent) clearance of apoptotic neutrophils by these cells. Ch25h and 25HC are, however, also robustly induced by lung-resident cells during the early hours of lung inflammation, suggesting additional cellular sources and targets.

Alveolar Biomarker Profiles in Subphenotypes of the Acute Respiratory Distress Syndrome.

Objectives: We sought to determine whether hyperinflammatory acute respiratory distress syndrome (ARDS) and hypoinflammatory ARDS, which have been associated with differences in plasma biomarkers and mortality risk, also display differences in bronchoalveolar lavage (BALF) biomarker profiles. We then described the relationship between hyperinflammatory ARDS and hypoinflammatory ARDS to novel subphenotypes derived using BALF biomarkers.

Design: Secondary analysis of a randomized control trial testing omega-3 fatty acids for the treatment of ARDS.

One Year Later: Family Members of Patients with COVID-19 Experience Persistent Symptoms of Posttraumatic Stress Disorder.

Family members of critically ill patients with coronavirus disease (COVID-19) have described increased symptoms of posttraumatic stress disorder (PTSD). Little is known about how these symptoms may change over time. We studied changes in PTSD symptoms in family members of critically ill patients with COVID-19 over 12 months.

Wellness and Coping of Physicians Who Worked in ICUs During the Pandemic: A Multicenter Cross-Sectional North American Survey.

Objectives: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic.

Design: Cross-sectional survey using four validated instruments.

Skeletal muscle macrophage ablation in mice.

Macrophages are important mediators of skeletal muscle function in both healthy and diseased states. In vivo specific depletion of macrophages provides an experimental method to understand physiological and pathophysiological effects of macrophages. Systemic depletion of macrophages can deplete skeletal muscle macrophages but also alters systemic inflammatory responses and metabolism, which confounds the muscle specific effects of macrophage depletion.

Skeletal Muscle Myofibers Directly Contribute to LPS-Induced Systemic Inflammatory Tone.

The abundance, anatomical distribution, and vascularity of skeletal muscle make it a potentially important contributor to local cytokine production and systemic cytokine abundance during inflammatory events. An orchestrated balance between the production of pro- and anti-inflammatory mediators is necessary for proper immune function, yet the contribution of the body's largest organ system, comprised primarily of skeletal muscle myocytes that fuse to form myofibers, to this process is largely unknown. Endotoxin (lipopolysaccharide, LPS) stimulates toll-like receptor 4 (TLR4) to induce the production of several pro-inflammatory cytokines, including interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2), by a of myriad cell types.

Stress-Related Disorders of Family Members of Patients Admitted to the Intensive Care Unit With COVID-19.

Importance: The psychological symptoms associated with having a family member admitted to the intensive care unit (ICU) during the COVID-19 pandemic are not well defined.

Objective: To examine the prevalence of symptoms of stress-related disorders, primarily posttraumatic stress disorder (PTSD), in family members of patients admitted to the ICU with COVID-19 approximately 90 days after admission.

Design, Setting, And Participants: This prospective, multisite, mixed-methods observational cohort study assessed 330 family members of patients admitted to the ICU (except in New York City, which had a random sample of 25% of all admitted patients per month) between February 1 and July 31, 2020, at 8 academic-affiliated and 4 community-based hospitals in 5 US states.

Content of Tele-Palliative Care Consultations with Patients Receiving Dialysis.

Little is known about the content of communication in palliative care telehealth conversations in the dialysis population. Understanding the content and process of these conversations may lead to insights about how palliative care improves quality of life. We conducted a qualitative analysis of video recordings obtained during a pilot palliative teleconsultation program.

Nutrition priorities in obese critically ill patients.

Purpose Of Review: During critical illness, several neuroendocrine, inflammatory, immune, adipokine, and gastrointestinal tract hormone pathways are activated; some of which are more intensified among obese compared with nonobese patients. Nutrition support may mitigate some of these effects. Nutrition priorities in obese critically ill patients include screening for nutritional risk, estimation of energy and protein requirement, and provision of macronutrients and micronutrients.

Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS-induced acute lung injury.

Muscle may contribute to the systemic inflammatory environment during critical illness, but leukocyte interaction and cytokine influence on muscle and its response has not been fully explored in this context. Using an in vivo model of intratracheal lipopolysaccharide (IT LPS)-induced acute lung injury, we show that skeletal muscle rapidly responds with expression of proinflammatory genes, which may be explained by migration of LPS into the circulation. Treatment of mature C2C12 myotubes with LPS at a level achieved in the circulation following IT LPS elicited a proinflammatory cytokine expression profile similar to that of in vivo murine muscle following IT LPS.

Feasibility and Acceptability of Telemedicine-Facilitated Palliative Care Consultations in Rural Dialysis Units.

Patients receiving dialysis have unmet palliative care needs. Limited access to palliative care is a key barrier to its integration into routine dialysis care. To determine the feasibility and acceptability of telepalliative care in rural dialysis units.

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

Purpose: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings.

Risk Factors for Cytomegalovirus Reactivation and Association With Outcomes in Critically Ill Adults With Sepsis: A Pooled Analysis of Prospective Studies.

We performed multivariable analysis of potential risk factors (including cytomegalovirus [CMV] reactivation) for clinical outcomes by day 28 (death or continued hospitalization, ventilator-free days, intensive care unit (ICU)-free days, hospital-free days) from pooled cohorts of 2 previous prospective studies of CMV-seropositive adults with sepsis. CMV reactivation at any level, >100 IU/mL, >1000 IU/mL, peak viral load, and area under the curve were independently associated with the clinical outcomes. We identified the potential effect size of CMV on outcomes that could be used as end points for future interventional trials of CMV prevention using antiviral prophylaxis in ICU patients with sepsis.

Kinetics and isotype assessment of antibodies targeting the spike protein receptor-binding domain of severe acute respiratory syndrome-coronavirus-2 in COVID-19 patients as a function of age, biological sex and disease severity.

Objectives: There is an incomplete understanding of the host humoral immune response to severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2, which underlies COVID-19, during acute infection. Host factors such as age and sex as well as the kinetics and functionality of antibody responses are important factors to consider as vaccine development proceeds. The receptor-binding domain of the CoV spike (RBD-S) protein mediates host cell binding and infection and is a major target for vaccine design to elicit neutralising antibodies.