Faculty Bibliography

BACKGROUND/UNASSIGNED:In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration. METHODS/UNASSIGNED:Patients with acute intermediate-risk PE admitted from October 2016 to July 2019 were included. CPES was calculated for each patient. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included individual components of the primary outcome. The association of CPES with primary and secondary outcomes was evaluated. RESULTS/UNASSIGNED:=0.005). CONCLUSIONS/UNASSIGNED:In patients with acute intermediate-risk PE, the CPES score effectively risk stratifies and prognosticates patients for the prediction of clinical events and provides incremental value over baseline demographics and European Society of Cardiology intermediate-risk subcategories.

INTRODUCTION/UNASSIGNED:Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. MATERIAL AND METHODS/UNASSIGNED:We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. RESULTS/UNASSIGNED:While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p<0.05), while there was no such association with antibody levels in the systemic circulation. DISCUSSION/UNASSIGNED:Our data highlight the critical role of local adaptive immunity in the airways as a key defence mechanism against primary SARS-CoV-2 infection.

BACKGROUND/UNASSIGNED:Clot-in-transit is associated with high mortality, but optimal management strategies remain uncertain. The aim of this study was to compare the outcomes of different treatment strategies in patients with clot-in-transit. METHODS/UNASSIGNED:This is a retrospective study of patients with documented clot-in-transit in the right heart on echocardiography across 2 institutions between January 2020 and October 2023. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. RESULTS/UNASSIGNED:=0.067). CONCLUSIONS/UNASSIGNED:In this study of CBT in patients with clot-in-transit, CBT or systemic thrombolysis was associated with a significantly lower rate of adverse clinical outcomes, including a lower rate of death compared with anticoagulation alone driven by the CBT group. CBT has the potential to improve outcomes. Further large-scale studies are needed to test these associations.

OBJECTIVES: Cather-directed therapies (CDTs) are an evolving therapeutic option for patients with intermediate-risk pulmonary embolism (PE). Although many techniques have been studied, there is limited evidence for the impact of timing of intervention on patient outcomes. Our objective was to assess the association between time to CDT in patients presenting with PE on patient-related outcomes such as length of stay (LOS) and mortality. DESIGN: Retrospective cohort study. SETTING: Single academic center. PATIENTS: We identified patients for which the PE response team had been activated from January 2014 to October 2021. Patients were split into two cohorts depending on whether they went to CDT less than 24 hours from admission (early) versus greater than 24 hours (late). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data on demographics, timing of interventions, pulmonary hemodynamics, and outcomes were collected. Sixty-four patients were included in analysis. Thirty-nine (63.8%) underwent their procedure less than 24 hours from admission, whereas 25 (36.2%) underwent the procedure after 24 hours. The time from admission to CDT was 15.9 hours (9.1-20.3 hr) in the early group versus 33.4 (27.9-41) in the late group (p ≤ 0.001). There was a greater decrease in pulmonary artery systolic pressure after intervention in the early cohort (14 mm Hg [6-20 mm Hg] vs 6 mm Hg [1-10 mm Hg]; p = 0.022). Patients who received earlier intervention were found to have shorter hospital LOS (4 vs 7 d; p = 0.038) and ICU LOS (3 vs 5 d; p = 0.004). There was no difference in inhospital mortality between the groups (17.9% vs 12%; p = 0.523). CONCLUSIONS: Patients who underwent CDT within 24 hours of admission were more likely to have shorter hospital and ICU LOS. The magnitude of change in LOS between the two cohorts was not fully explained by the difference in time to CDT. There were modest improvements in pulmonary hemodynamics in the patients who underwent CDT earlier.

OBJECTIVES/OBJECTIVE:This study sought to evaluate the efficacy and safety of tissue-plasminogen activator (t-PA) infused via a Pharmacomechanical catheter-directed thrombolysis (PM-CDT) device called the Bashir Catheter in intermediate-risk acute pulmonary embolism (PE) patients. BACKGROUND:Catheter-directed thrombolysis (CDT) has been associated with rapid recovery of right ventricular (RV) function. The Bashir catheter was developed for enhanced thrombolysis in large vessels like the pulmonary artery (PA) with lower doses of t-PA. METHODS:Patients with symptoms of acute PE with CT evidence of RV dilatation were enrolled. The Bashir Catheter was used to deliver 7 mgs of t-PA into each PA over 5 hours. The primary efficacy endpoint was the core laboratory assessed change in CTA-derived right ventricular/left ventricular (RV/LV) diameter ratio at 48 hours and the primary safety endpoint was serious adverse events including major bleeding at 72 hours. RESULTS:At 18 US sites, 109 patients were enrolled. The median device placement time was 15 minutes. At 48 hours after PM-CDT the RV/LV ratio decreased by 0.56 (33.3%: p<0.0001). The PA obstruction as measured by the Refined Modified Miller Index (RMMI) was reduced by 35.9% (p <0.0001). One patient (0.92%) had two serious adverse events (SAE) which included a retroperitoneal bleed (procedure-related) and iliac vein thrombosis (device-related). Two other procedure-related SAEs included epistaxis, and non-access site hematoma with anemia. CONCLUSIONS:PM-CDT with the Bashir endovascular catheter is associated with significant reduction in RV/LV ratio and a very low rate of adverse events or major bleeding in intermediate-risk acute PE patients. The notable finding was a significant reduction in PA obstruction with low dose t-PA. (Recombinant tPA by Endovascular Administration for the treatment of Submassive pulmonary embolism using pharmaco-mechanical Catheter directed thrombolysis for the redUction of thrombus burdEn - The RESCUE Study IDE # G200009 NCT - 04248868).

BACKGROUND:The impact of pulmonary embolism response teams (PERTs) on treatment choice and outcomes of patients with acute pulmonary embolism (PE) is still uncertain. OBJECTIVE:To determine the effect of PERTs in the management and outcomes of patients with PE. METHODS:PubMed, Embase, Web of Science, CINAHL, WorldWideScience and MedRxiv were searched for original articles reporting PERT patient outcomes from 2009. Data were analysed using a random effects model. RESULTS:16 studies comprising 3827 PERT patients and 3967 controls met inclusion criteria. The PERT group had more patients with intermediate and high-risk PE (66.2%) compared to the control group (48.5%). Meta-analysis demonstrated an increased risk of catheter-directed interventions, systemic thrombolysis and surgical embolectomy (odds ratio (OR) 2.10, 95% confidence interval (CI) 1.74-2.53; p<0.01), similar bleeding complications (OR 1.10, 95% CI 0.88-1.37) and decreased utilisation of inferior vena cava (IVC) filters (OR 0.71, 95% CI 0.58-0.88; p<0.01) in the PERT group. Furthermore, there was a nonsignificant trend towards decreased mortality (OR 0.87, 95% CI 0.71-1.07; p=0.19) with PERTs. CONCLUSIONS:The PERT group showed an increased use of advanced therapies and a decreased utilisation of IVC filters. This was not associated with increased bleeding. Despite comprising more severe PE patients, there was a trend towards lower mortality in the PERT group.

BACKGROUND/UNASSIGNED:Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE/UNASSIGNED:The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS/UNASSIGNED:This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS/UNASSIGNED:= 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS/UNASSIGNED:In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

PURPOSE/OBJECTIVE:Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS:ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS:, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION/CONCLUSIONS:Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.

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.