Rationale: The contributions of diverse cell populations in the human lung to pulmonary fibrosis pathogenesis are poorly understood. Single-cell RNA sequencing can reveal changes within individual cell populations during pulmonary fibrosis that are important for disease pathogenesis. Objectives: To determine whether single-cell RNA sequencing can reveal disease-related heterogeneity within alveolar macrophages, epithelial cells, or other cell types in lung tissue from subjects with pulmonary fibrosis compared with control subjects. Methods: We performed single-cell RNA sequencing on lung tissue obtained from eight transplant donors and eight recipients with pulmonary fibrosis and on one bronchoscopic cryobiospy sample from a patient with idiopathic pulmonary fibrosis. We validated these data using in situ RNA hybridization, immunohistochemistry, and bulk RNA-sequencing on flow-sorted cells from 22 additional subjects. Measurements and Main Results: We identified a distinct, novel population of profibrotic alveolar macrophages exclusively in patients with fibrosis. Within epithelial cells, the expression of genes involved in Wnt secretion and response was restricted to nonoverlapping cells. We identified rare cell populations including airway stem cells and senescent cells emerging during pulmonary fibrosis. We developed a web-based tool to explore these data. Conclusions: We generated a single-cell atlas of pulmonary fibrosis. Using this atlas, we demonstrated heterogeneity within alveolar macrophages and epithelial cells from subjects with pulmonary fibrosis. These results support the feasibility of discovery-based approaches using next-generation sequencing technologies to identify signaling pathways for targeting in the development of personalized therapies for patients with pulmonary fibrosis.
Misharin et al. elucidate the fate and function of monocyte-derived alveolar macrophages during the course of pulmonary fibrosis. These cells persisted throughout the life span, were enriched for the expression of profibrotic genes, and their genetic ablation ameliorated development of pulmonary fibrosis.
Objectives The goal of this study was to determine the association of first pass success with the incidence of adverse events (AEs) during emergency department (ED) intubations. Methods This was a retrospective analysis of prospectively collected continuous quality improvement data based on orotracheal intubations performed in an academic ED over a 4-year period. Following each intubation, the operator completed a data form regarding multiple aspects of the intubation, including patient and operator characteristics, method of intubation, device used, the number of attempts required, and AEs. Numerous AEs were tracked and included events such as witnessed aspiration, oxygen desaturation, esophageal intubation, hypotension, dysrhythmia, and cardiac arrest. Multivariable logistic regression was used to assess the relationship between the primary predictor variable of interest, first pass success, and the outcome variable, the presence of one or more AEs, after controlling for various other potential risk factors and confounders. Results Over the 4-year study period, there were 1,828 orotracheal intubations. If the intubation was successful on the first attempt, the incidence of one or more AEs was 14.2% (95% confidence interval [CI] = 12.4% to 16.2%). In cases requiring two attempts, the incidence of one or more AEs was 47.2% (95% CI = 41.8% to 52.7%); in cases requiring three attempts, the incidence of one or more AEs was 63.6% (95% CI = 53.7% to 72.6%); and in cases requiring four or more attempts, the incidence of one or more AEs was 70.6% (95% CI = 56.2.3% to 82.5%). Multivariable logistic regression showed that more than one attempt at tracheal intubation was a significant predictor of one or more AEs (adjusted odds ratio [aOR] = 7.52, 95% CI = 5.86 to 9.63). Conclusions When performing orotracheal intubation in the ED, first pass success is associated with a relatively small incidence of AEs. As the number of attempts increases, the incidence of AEs increases substantially.
The coronavirus disease 2019 (COVID-19) pandemic has changed health care delivery worldwide. Although decreases in hospitalization for acute myocardial infarction (AMI) have been reported during the pandemic, the implication for in-hospital outcomes is not well understood. OBJECTIVE To define changes in AMI case rates, patient demographics, cardiovascular comorbidities, treatment approaches, and in-hospital outcomes during the pandemic. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study retrospectively analyzed AMI hospitalizations that occurred between December 30, 2018, and May 16, 2020, in 1 of the 49 hospitals in the Providence St Joseph Health system located in 6 states (Alaska, Washington, Montana, Oregon, California, and Texas). The cohort included patients aged 18 years or older who had a principal discharge diagnosis of AMI (ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI]). Segmented regression analysis was performed to assess changes in weekly case volumes. Cases were grouped into 1 of 3 periods:
Study objective We determine the proportion of successful intubations with the C-MAC video laryngoscope (C-MAC) compared with the direct laryngoscope in emergency department (ED) intubations. Methods This was a retrospective analysis of prospectively collected data entered into a continuous quality improvement database during a 28-month period in an academic ED. After each intubation, the operator completed a standardized data form evaluating multiple aspects of the intubation, including patient demographics, indication for intubation, device(s) used, reason for device selection, difficult airway characteristics, number of attempts, and outcome of each attempt. Intubation was considered ultimately successful if the endotracheal tube was correctly inserted into the trachea with the initial device. An attempt was defined as insertion of the device into the mouth regardless of whether there was an attempt to pass the tube. The primary outcome measure was ultimate success. Secondary outcome measures were first-attempt success, Cormack-Lehane view, and esophageal intubation. Multivariate logistic regression analyses, with the inclusion of a propensity score, were performed for the outcome variables ultimate success and first-attempt success. Results During the 28-month study period, 750 intubations were performed with either the C-MAC with a size 3 or 4 blade or a direct laryngoscope with a Macintosh size 3 or 4 blade. Of these, 255 were performed with the C-MAC as the initial device and 495 with a Macintosh direct laryngoscope as the initial device. The C-MAC resulted in successful intubation in 248 of 255 cases (97.3%; 95% confidence interval [CI] 94.4% to 98.9%). A direct laryngoscope resulted in successful intubation in 418 of 495 cases (84.4%; 95% CI 81.0% to 87.5%). In the multivariate regression model, with a propensity score included, the C-MAC was positively predictive of ultimate success (odds ratio 12.7; 95% CI 4.1 to 38.8) and first-attempt success (odds ratio 2.2; 95% CI 1.2 to 3.8). When the C-MAC was used as a video laryngoscope, a Cormack-Lehane grade I or II view (video) was obtained in 117 of 125 cases (93.6%; 95% CI 87.8% to 97.2%), whereas when a direct laryngoscope was used, a grade I or II view was obtained in 410 of 495 cases (82.8%; 95% CI 79.2% to 86.1%). The C-MAC was associated with immediately recognized esophageal intubation in 4 of 255 cases (1.6%; 95% CI 0.4% to 4.0%), whereas a direct laryngoscope was associated with immediately recognized esophageal intubation in 24 of 495 cases (4.8%; 95% CI 3.1% to 7.1%). Conclusion When used for emergency intubations in the ED, the C-MAC was associated with a greater proportion of successful intubations and a greater proportion of Cormack-Lehane grade I or II views compared with a direct laryngoscope.
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