Impact of Atrial Fibrillation on In-Hospital Mortality and Thromboembolic Complications after Left Ventricular Assist Device Implantation.

The association between atrial fibrillation (AF) and thromboembolic (TE) complications in left ventricular assist device (LVAD) recipients is controversial, and there is paucity of large-scale data evaluating the impact of AF on early outcomes after device implantation. Using the National Inpatient Sample, we identified hospitalizations where patients underwent LVAD implantation from 2010 to 2015. Multivariate logistic regression was used to evaluate the association of AF on in-hospital outcomes. A total of 18,378 patients (41.7% with AF) underwent LVAD implantation. Patients with AF were older (59.9 vs. 54.0 years, p < 0.001), more commonly male (79.9 vs. 74.1%, p < 0.001), and had a greater burden of comorbidities as measured by the Elixhauser comorbidity index (7.2 vs. 6.3, p < 0.001). Patients with AF had less incidence of ischemic stroke (3.1 vs. 4.7%, p = 0.04, OR 0.68), hemorrhagic stroke (1.0 vs. 2.4%, p = 0.006, OR 0.43), and other systemic embolism (1.8 vs. 3.7%, p = 0.01, OR 0.55). There was no significant difference in the incidence of bleeding requiring transfusion between AF and no AF cohorts (29.3 vs. 24.2%, p = 0.09, OR 1.15). LOS was shorter in patients with AF (32.9 vs. 36.7 mean days, p < 0.001). Patients with AF had lower in-hospital mortality (8.9 vs. 14.9%, p < 0.001, OR 0.48). In a large real-world US cohort of patients undergoing LVAD implantation, a diagnosis of AF was common among device recipients. After adjustment for demographics and comorbidities, AF was associated with reduced TE events and in-hospital mortality.

Lack of airway submucosal glands impairs respiratory host defenses.

Submucosal glands (SMGs) are a prominent structure that lines human cartilaginous airways. Although it has been assumed that SMGs contribute to respiratory defense, that hypothesis has gone without a direct test. Therefore, we studied pigs, which have lungs like humans, and disrupted the gene for ectodysplasin (EDA-KO), which initiates SMG development. EDA-KO pigs lacked SMGs throughout the airways. Their airway surface liquid had a reduced ability to kill bacteria, consistent with SMG production of antimicrobials. In wild-type pigs, SMGs secrete mucus that emerges onto the airway surface as strands. Lack of SMGs and mucus strands disrupted mucociliary transport in EDA-KO pigs. Consequently, EDA-KO pigs failed to eradicate a bacterial challenge in lung regions normally populated by SMGs. These in vivo and ex vivo results indicate that SMGs are required for normal antimicrobial activity and mucociliary transport, two key host defenses that protect the lung.

Heterogeneous expression of the SARS-Coronavirus-2 receptor ACE2 in the human respiratory tract.

BACKGROUND: Zoonotically transmitted coronaviruses are responsible for three disease outbreaks since 2002, including the current COVID-19 pandemic, caused by SARS-CoV-2. Its efficient transmission and range of disease severity raise questions regarding the contributions of virus-receptor interactions. ACE2 is a host ectopeptidase and the receptor for SARS-CoV-2. Numerous reports describe ACE2 mRNA abundance and tissue distribution; however, mRNA abundance is not always representative of protein levels. Currently, there is limited data evaluating ACE2 protein and its correlation with other SARS-CoV-2 susceptibility factors. MATERIALS AND METHODS: We systematically examined the human upper and lower respiratory tract using single-cell RNA sequencing and immunohistochemistry to determine receptor expression and evaluated its association with risk factors for severe COVID-19. FINDINGS: Our results reveal that ACE2 protein is highest within regions of the sinonasal cavity and pulmonary alveoli, sites of presumptive viral transmission and severe disease development, respectively. In the lung parenchyma, ACE2 protein was found on the apical surface of a small subset of alveolar type II cells and colocalized with TMPRSS2, a cofactor for SARS-CoV2 entry. ACE2 protein was not increased by pulmonary risk factors for severe COVID-19. Additionally, ACE2 protein was not reduced in children, a demographic with a lower incidence of severe COVID-19. INTERPRETATION: These results offer new insights into ACE2 protein localization in the human respiratory tract and its relationship with susceptibility factors to COVID-19.