Faculty Bibliography

Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.

Lung transplant is increasingly performed for the treatment of end-stage lung disease. As the number of lung transplants and transplant centers continues to rise, radiologists will more frequently participate in the care of patients undergoing lung transplant, both before and after transplant. Potential donors and recipients undergo chest radiography and CT as part of their pretransplant assessment to evaluate for contraindications to transplant and to aid in surgical planning. After transplant, recipients undergo imaging during the postoperative hospitalization and also in the long-term outpatient setting. Radiologists encounter a wide variety of conditions leading to end-stage lung disease and a myriad of posttransplant complications, some of which are unique to lung transplantation. Familiarity with these pathologic conditions, including their imaging findings and their temporal relationship to the transplant, is crucial to accurate radiologic interpretation. Knowledge of the surgical techniques and expected postoperative appearance prevents confusing normal posttransplant imaging findings with complications. A basic understanding of the indications, contraindications, and surgical considerations of lung transplant aids in imaging interpretation and protocoling and also facilitates communication between radiologists and transplant physicians. Despite medical and surgical advances over the past several decades, lung transplant recipients currently have an average posttransplant life expectancy of only 6.7 years. As members of the transplant team, radiologists can help maximize patient survival and hopefully increase posttransplant life expectancy and quality of life in the coming decades. ^©RSNA, 2021 An invited commentary by Bierhals is available online. Online supplemental material is available for this article.

OBJECTIVES/OBJECTIVE:To assess the impact of percutaneous dilational tracheostomy in coronavirus disease 2019 patients requiring mechanical ventilation and the risk for healthcare providers. DESIGN/METHODS:Prospective cohort study; patients were enrolled between March 11, and April 29, 2020. The date of final follow-up was July 30, 2020. We used a propensity score matching approach to compare outcomes. Study outcomes were formulated before data collection and analysis. SETTING/METHODS:Critical care units at two large metropolitan hospitals in New York City. PATIENTS/METHODS:Five-hundred forty-one patients with confirmed severe coronavirus disease 2019 respiratory failure requiring mechanical ventilation. INTERVENTIONS/METHODS:Bedside percutaneous dilational tracheostomy with modified visualization and ventilation. MEASUREMENTS AND MAIN RESULTS/RESULTS:Required time for discontinuation off mechanical ventilation, total length of hospitalization, and overall patient survival. Of the 541 patients, 394 patients were eligible for a tracheostomy. One-hundred sixteen were early percutaneous dilational tracheostomies with median time of 9 days after initiation of mechanical ventilation (interquartile range, 7-12 d), whereas 89 were late percutaneous dilational tracheostomies with a median time of 19 days after initiation of mechanical ventilation (interquartile range, 16-24 d). Compared with patients with no tracheostomy, patients with an early percutaneous dilational tracheostomy had a higher probability of discontinuation from mechanical ventilation (absolute difference, 30%; p < 0.001; hazard ratio for successful discontinuation, 2.8; 95% CI, 1.34-5.84; p = 0.006) and a lower mortality (absolute difference, 34%, p < 0.001; hazard ratio for death, 0.11; 95% CI, 0.06-0.22; p < 0.001). Compared with patients with late percutaneous dilational tracheostomy, patients with early percutaneous dilational tracheostomy had higher discontinuation rates from mechanical ventilation (absolute difference 7%; p < 0.35; hazard ratio for successful discontinuation, 1.53; 95% CI, 1.01-2.3; p = 0.04) and had a shorter median duration of mechanical ventilation in survivors (absolute difference, -15 d; p < 0.001). None of the healthcare providers who performed all the percutaneous dilational tracheostomies procedures had clinical symptoms or any positive laboratory test for severe acute respiratory syndrome coronavirus 2 infection. CONCLUSIONS:In coronavirus disease 2019 patients on mechanical ventilation, an early modified percutaneous dilational tracheostomy was safe for patients and healthcare providers and associated with improved clinical outcomes.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

Importance/UNASSIGNED:Decision-making in the timing of tracheostomy in patients with coronavirus disease 2019 (COVID-19) has centered on the intersection of long-standing debates on the benefits of early vs late tracheostomy, assumptions about timelines of infectivity of the novel coronavirus, and concern over risk to surgeons performing tracheostomy. Multiple consensus guidelines recommend avoiding or delaying tracheostomy, without evidence to indicate anticipated improvement in outcomes as a result. Objective/UNASSIGNED:To assess outcomes from early tracheostomy in the airway management of patients with COVID-19 requiring mechanical ventilation. Design, Setting, and Participants/UNASSIGNED:A retrospective medical record review was completed of 148 patients with reverse transcriptase-polymerase chain reaction-confirmed COVID-19 requiring mechanical ventilation at a single tertiary-care medical center in New York City from March 1 to May 7, 2020. Interventions/UNASSIGNED:Open or percutaneous tracheostomy. Main Outcomes and Measures/UNASSIGNED:The primary outcomes were time from symptom onset to (1) endotracheal intubation, (2) tracheostomy; time from endotracheal intubation to tracheostomy; time from tracheostomy to (1) tracheostomy tube downsizing, (2) decannulation; total time on mechanical ventilation; and total length of stay. Results/UNASSIGNED:Participants included 148 patients, 120 men and 28 women, with an overall mean (SD) age of 58.1 (15.8) years. Mean (SD; median) time from symptom onset to intubation was 10.57 (6.58; 9) days; from symptom onset to tracheostomy, 22.76 (8.84; 21) days; and from endotracheal intubation to tracheostomy, 12.23 (6.82; 12) days. The mean (SD; median) time to discontinuation of mechanical ventilation was 33.49 (18.82; 27) days; from tracheostomy to first downsize, 23.02 (13.76; 19) days; and from tracheostomy to decannulation, 30.16 (16.00; 26) days. The mean (SD; median) length of stay for all patients was 51.29 (23.66; 45) days. Timing of tracheostomy was significantly associated with length of stay: median length of stay was 40 days in those who underwent early tracheostomy (within 10 days of endotracheal intubation) and 49 days in those who underwent late tracheostomy (median difference, -8; 95% CI, -15 to -1). In a competing risks model with death as the competing risk, the late tracheostomy group was 16% less likely to discontinue mechanical ventilation (hazard ratio, 0.84; 95% CI, 0.55 to 1.28). Conclusions and Relevance/UNASSIGNED:This cohort study from the first 2 months of the pandemic in New York City provides an opportunity to reconsider guidelines for tracheostomy for patients with COVID-19. Findings demonstrated noninferiority of early tracheostomy and challenges recommendations to categorically delay or avoid tracheostomy in this patient population. When aligned with emerging evidence about the timeline of infectivity of the novel coronavirus, this approach may optimize outcomes from tracheostomy while keeping clinicians safe.

BACKGROUND:The lung allocation score (LAS) was designed to optimize the utilization of pulmonary allografts based on anticipated pre-transplant survival and post-transplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regards to organ allocation. The objective of this study was to determine if pre-transplant hospital admission status is independently associated with post-transplant mortality and to determine if high center volume is associated with improved survival in that cohort.background METHODS: All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Group stratification was performed based on admission status at the time of transplantation. A Cox proportional hazard regression was used to determine independent associations with post-transplant mortality. RESULTS:During the study period, 20% (3,747/18,416) of recipients were admitted to the hospital at the time of transplantation. Compared to non-admitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of post-transplant dialysis, and longer post-transplant lengths of stay. Pre-transplant admission to a low volume center conferred significantly worse survival compared to non-admitted patients, and high volume centers were independently associated with improved survival compared to low volume centers.results CONCLUSIONS: Hospital admission status is associated with increased post-transplant mortality independent from the LAS and the factors from which it is calculated. However, adjusted survival analysis demonstrates that admission to a high volume center appears to be independently associated with improved survival compared to low volume centers. CONCLUSION/CONCLUSIONS/:

BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS≥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.