Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) usually results in respiratory disease, but extrapulmonary manifestations are of major clinical interest. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Human induced pluripotent stem cell-derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium.

SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation.

Patients with coronavirus disease 2019 (COVID-19) present a wide range of acute clinical manifestations affecting the lungs, liver, kidneys and gut. Angiotensin converting enzyme (ACE) 2, the best-characterized entry receptor for the disease-causing virus SARS-CoV-2, is highly expressed in the aforementioned tissues. However, the pathways that underlie the disease are still poorly understood.

SARS-CoV-2 induces double-stranded RNA-mediated innate immune responses in respiratory epithelial-derived cells and cardiomyocytes.

Coronaviruses are adept at evading host antiviral pathways induced by viral double-stranded RNA, including interferon (IFN) signaling, oligoadenylate synthetase-ribonuclease L (OAS-RNase L), and protein kinase R (PKR). While dysregulated or inadequate IFN responses have been associated with severe coronavirus infection, the extent to which the recently emerged SARS-CoV-2 activates or antagonizes these pathways is relatively unknown. We found that SARS-CoV-2 infects patient-derived nasal epithelial cells, present at the initial site of infection; induced pluripotent stem cell-derived alveolar type 2 cells (iAT2), the major cell type infected in the lung; and cardiomyocytes (iCM), consistent with cardiovascular consequences of COVID-19 disease.

Differences in Family Involvement in the Bedside Care of Patients in the ICU Based on Self-Identified Race.

Objectives: Being a caregiver for a patient in the ICU can place emotional burden on families and engaging families in caregiving can reduce psychological distress. Our goal was to observe support methods used by families in the ICU and identify differences between race/ethnicity.

Design: A secondary analysis of a multicenter before-and-after clinical trial.

Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report.

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic.

Materials And Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed.

Comparing nurse leader and manager perceptions of and strategies for nurse engagement using a positive deviance approach: A qualitative analysis.

Aims: To understand nurse leader and manager perspectives on employee engagement and their own role to foster engagement. To examine differences between managers of units with high versus low engagement.

Background: Health systems recognize the impact of employee engagement, yet alignment of leader and frontline-manager perspectives remains unclear.

Long-term tolerability of phosphodiesterase-5 inhibitors in pulmonary hypertension of sickle cell disease.

Objectives: Sickle cell disease-related pulmonary hypertension (SCD-PH) is a complex disorder with multifactorial contributory mechanisms. Previous trials have evaluated the efficacy of pulmonary arterial hypertension (PAH) therapies in SCD-PH with mixed results. We hypothesized that a subset of patients with right heart catheterization (RHC) confirmed disease may benefit from PAH therapy.

Rationale and Design of the Awake Prone Position for Early Hypoxemia in COVID-19 Study Protocol: A Clinical Trial.

The unprecedented public health burdens of coronavirus disease (COVID-19) have intensified the urgency of identifying effective, low-cost treatments that limit the need for advanced life support measures and improve clinical outcomes. However, personal protective equipment and staffing shortages, disease virulence, and infectivity have created significant barriers to traditional clinical trial practices. We present the novel design of a pragmatic, adaptive, multicenter, international, prospective randomized controlled clinical trial evaluating the safety and effectiveness of awake prone positioning in spontaneously breathing patients with COVID-19 (APPEX-19 [Awake Prone Position for Early Hypoxemia in COVID-19]).

Professional Societies' Role in Addressing Member Burnout and Promoting Well-Being.

Critical care clinicians have high burnout rates. Previous studies have explored individual and organizational solutions to address burnout, but existing literature has not considered how professional societies can prevent burnout and promote member well-being. The Critical Care Society Collaborative convened a task force to document professional society initiatives to address burnout, explore perspectives on the role of societies to address burnout, and develop recommendations that could guide critical care societies' efforts to promote well-being.

Access to Lung Cancer Screening in the Veterans Health Administration: Does Geographic Distribution Match Need in the Population?

Background: Studies show uneven access to Medicare-approved lung cancer screening (LCS) programs across the United States. The Veterans Health Administration (VA), the largest national US integrated health system, is potentially well positioned to coordinate LCS services across regional units to ensure that access matches distribution of need nationally.

Research Question: To what extent does LCS access (considering both VA and partner sites) and use match the distribution of eligible Veterans at state and regional levels?

Methods: In this retrospective analysis, we identified LCS examinations in VA facilities between 2013 and 2019 from the VA Corporate Data Warehouse and plotted VA facilities with LCS geographically.

Critical Care of Patients With Cardiopulmonary Complications of Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease defined by the presence of aberrant granulomas affecting various organs. Due to its multisystem involvement, care of patients with established sarcoidosis becomes challenging, especially in the intensive care setting. While the lungs are typically involved, extrapulmonary manifestations also occur either concurrently or exclusively within a significant proportion of patients, complicating diagnostic and management decisions.

Development and Validation of an Automated Algorithm to Detect Atrial Fibrillation Within Stored Intensive Care Unit Continuous Electrocardiographic Data: Observational Study.

Background: Atrial fibrillation (AF) is the most common arrhythmia during critical illness, representing a sepsis-defining cardiac dysfunction associated with adverse outcomes. Large burdens of premature beats and noisy signal during sepsis may pose unique challenges to automated AF detection.

Objective: The objective of this study is to develop and validate an automated algorithm to accurately identify AF within electronic health care data among critically ill patients with sepsis.

Clinical predictors of poor outcomes in patients with sickle cell disease and COVID-19 infection.

We aimed to identify predictors of outcomes and survival in patients living in 4 major metropolitan areas who had sickle cell disease (SCD) and COVID-19 to inform best approaches to prevention and care. Data were collected at baseline and during the clinical course in SCD patients diagnosed with COVID-19 in four COVID-19 epicenters. Patients were followed up posthospital discharge for up to 3 months.

Guideline-Concordant Insulin Infusion Initiation Among Critically Ill Patients With Sepsis.

Objective: Our objective was to benchmark rates of guideline-concordant insulin infusion initiation, identify factors associated with guideline-concordant insulin practices, and examine the association between hospital-level guideline concordance and mortality among critically ill patients with sepsis.

Methods: We performed a multicenter retrospective cohort study of intensive care patients with sepsis who were eligible for insulin infusion initiation according to American Diabetes Association and Surviving Sepsis guidelines (persistent blood sugar ≥180 mg/dL). We then identified patients who were initiated on insulin infusions within 24 hours of eligibility.

Organizational Readiness for Lung Cancer Screening: A Cross-Sectional Evaluation at a Veterans Affairs Medical Center.

Objectives: Lung cancer has the highest cancer-related mortality in the United States and among Veterans. Screening of high-risk individuals with low-dose CT (LDCT) can improve survival through detection of early-stage lung cancer. Organizational factors that aid or impede implementation of this evidence-based practice in diverse populations are not well described.

Development and Validation of Algorithms to Identify Pulmonary Arterial Hypertension in Administrative Data.

Background: Pulmonary arterial hypertension (PAH) is a rare disease, and much of our understanding stems from single-center studies, which are limited by sample size and generalizability. Administrative data offer an appealing opportunity to inform clinical, research, and quality improvement efforts for PAH. Yet, currently no standardized, validated method exists to distinguish PAH from other subgroups of pulmonary hypertension (PH) within this data source.

Variation in Eligible Patients' Agreeing to and Receiving Lung Cancer Screening: A Cohort Study.

Introduction: Little is known about how clinicians make low-dose computed tomography lung cancer screening decisions in practice. Investigators assessed the factors associated with real-world decision making, hypothesizing that lung cancer risk and comorbidity would not be associated with agreeing to or receiving screening. Though these factors are key determinants of the benefit of lung cancer screening, they are often difficult to incorporate into decisions without the aid of decision tools.

Management Strategies to Promote Follow-Up Care for Incidental Findings: A Scoping Review.

Background: Incidentalomas, or unexpectedly identified masses, are frequently identified in diagnostic imaging studies. Incidentalomas may require timely follow-up care to determine if they are benign, disease-causing, or malignant lesions; however, many incidentalomas do not receive diagnostic workup. The most effective strategies to manage incidentalomas and optimal metrics for judging the efficacy of these strategies remain unclear.

Stability of Do-Not-Resuscitate Orders in Hospitalized Adults: A Population-Based Cohort Study.

Objectives: Prior work has shown substantial between-hospital variation in do-not-resuscitate orders, but stability of do-not-resuscitate preferences between hospitalizations and the institutional influence on do-not-resuscitate reversals are unclear. We determined the extent of do-not-resuscitate reversals between hospitalizations and the association of the readmission hospital with do-not-resuscitate reversal.

Design: Retrospective cohort study.

Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2.

Human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen of the COVID-19 pandemic, exerts a massive health and socioeconomic crisis. The virus infects alveolar epithelial type 2 cells (AT2s), leading to lung injury and impaired gas exchange, but the mechanisms driving infection and pathology are unclear. We performed a quantitative phosphoproteomic survey of induced pluripotent stem cell-derived AT2s (iAT2s) infected with SARS-CoV-2 at air-liquid interface (ALI).

Tobacco Treatment Program Models in US Hospitals and Outpatient Centers on Behalf of the SRNT Treatment Network.

Because tobacco use remains one of the leading causes of disease, disability, and mortality, tobacco treatment programs should be integrated into medical systems such as hospitals and outpatient centers. Medical providers have a unique, high-impact opportunity to initiate smoking cessation treatment with patients. However, there are several barriers that may hinder the development and implementation of these programs.

Guidelines for the Evaluation of Pulmonary Nodules Detected Incidentally or by Screening: A Survey of Radiologist Awareness, Agreement, and Adherence From the Watch the Spot Trial.

Purpose: The aim of this study was to examine radiologists' beliefs about existing guidelines for pulmonary nodule evaluation.

Methods: A self-administered survey was developed to ascertain awareness of, agreement with, and adherence to published guidelines, including those from the Fleischner Society and the Lung CT Screening Reporting and Data System (Lung-RADS™). Surveys were distributed to 514 radiologists at 13 health care systems that are participating in a large, pragmatic trial of pulmonary nodule evaluation.

Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018.

Importance: Generating robust and timely evidence about the respiratory health risks of electronic cigarettes (e-cigarettes) is critical for informing state and federal regulatory standards for product safety.

Objective: To examine the association of e-cigarette use with incident respiratory conditions, including chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, and asthma.

Design, Setting, And Participants: This prospective cohort study used data from the nationally representative cohort of US adults from the Population Assessment of Tobacco and Health (PATH) study, including wave 1 from 2013 to 2014, wave 2 from 2014 to 2015, wave 3 from 2015 to 2016, and wave 4 from 2016 to 2018.

Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells.

The derivation of tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would have broad reaching implications for regenerative medicine. Here, we report the directed differentiation of human iPSCs into airway basal cells ("iBCs"), a population resembling the stem cell of the airway epithelium. Using a dual fluorescent reporter system (NKX2-1;TP63), we track and purify these cells as they first emerge as developmentally immature NKX2-1 lung progenitors and subsequently augment a TP63 program during proximal airway epithelial patterning.