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Adjusting positive end-expiratory pressure (PEEP) to offset pleural pressure might attenuate lung injury and improve patient outcomes in acute respiratory distress syndrome (ARDS).To determine whether PEEP titration guided by esophageal pressure (PES), an estimate of pleural pressure, was more effective than empirical high PEEP-fraction of inspired oxygen (Fio2) in moderate to severe ARDS.Phase 2 randomized clinical trial conducted at 14 hospitals in North America. Two hundred mechanically ventilated patients aged 16 years and older with moderate to severe ARDS (Pao2:Fio2 ≤200 mm Hg) were enrolled between October 31, 2012, and September 14, 2017; long-term follow-up was completed July 30, 2018.Participants were randomized to PES-guided PEEP (n = 102) or empirical high PEEP-Fio2 (n = 98). All participants received low tidal volumes.The primary outcome was a ranked composite score incorporating death and days free from mechanical ventilation among survivors through day 28. Prespecified secondary outcomes included 28-day mortality, days free from mechanical ventilation among survivors, and need for rescue therapy.Two hundred patients were enrolled (mean [SD] age, 56 [16] years; 46% female) and completed 28-day follow-up. The primary composite end point was not significantly different between treatment groups (probability of more favorable outcome with PES-guided PEEP: 49.6% [95% CI, 41.7% to 57.5%]; P = .92). At 28 days, 33 of 102 patients (32.4%) assigned to PES-guided PEEP and 30 of 98 patients (30.6%) assigned to empirical PEEP-Fio2 died (risk difference, 1.7% [95% CI, -11.1% to 14.6%]; P = .88). Days free from mechanical ventilation among survivors was not significantly different (median [interquartile range]: 22 [15-24] vs 21 [16.5-24] days; median difference, 0 [95% CI, -1 to 2] days; P = .85). Patients assigned to PES-guided PEEP were significantly less likely to receive rescue therapy (4/102 [3.9%] vs 12/98 [12.2%]; risk difference, -8.3% [95% CI, -15.8% to -0.8%]; P = .04). None of the 7 other prespecified secondary clinical end points were significantly different. Adverse events included gross barotrauma, which occurred in 6 patients with PES-guided PEEP and 5 patients with empirical PEEP-Fio2.Among patients with moderate to severe ARDS, PES-guided PEEP, compared with empirical high PEEP-Fio2, resulted in no significant difference in death and days free from mechanical ventilation. These findings do not support PES-guided PEEP titration in ARDS.ClinicalTrials.gov Identifier NCT01681225.

Introduction: As the management of COVID-19 has continued to evolve, the question as to whether delaying intubation is beneficial or harmful for patients with COVID-19 induced hypoxic respiratory failure has yet to be answered. Early reports suggested that patients may benefit from early intubation during a period of severe hypoxia;later management shifted towards delaying intubation as much as possible using non-invasive ventilation. Additionally, the pathophysiologic implications of timing of intubation are poorly understood, including the potential for pulmonary vascular thrombosis and intussusceptive angiogenesis. This study examines the differences in outcomes and respiratory mechanics between subjects who are intubated earlier versus later in their COVID-19 disease course. Study Design and Methods: Retrospective single-center cohort study of subjects intubated for COVID-19 ARDS between March and June 2020. Patients were stratified by time to intubation: 30 subjects were intubated 4-24 hours after presentation and 24 subjects were intubated 5-10 days after presentation. Data regarding baseline characteristics, hospitalization, ventilator mechanics and outcomes were extracted and analyzed. 10 clinically available CT scans for these patients were manually reviewed to identify evidence of pulmonary vascular thrombosis and intussusceptive angiogenesis. Results: Median time from symptom onset to intubation was significantly different between the Early and Late Intubation Cohorts, with the latter being intubated later in the course of their illness (7.9 days vs 11.8 days;p=0.04). The Early Intubation Cohort had a lower mortality rate than the Late Intubation Cohort (6% vs 30%, p < 0.001) without significantly different ventilator mechanics at the time of intubation. However, the Late Intubation Cohort was noted to have higher dead space ratio (0.40 vs 0.52;p = 0.03). On review of CT scans, the Late Intubation Cohort also had more segments with dilated and tortuous peripheral vessels on imaging (2 segments vs 5 segments). Interpretation: As our approaches to treatment of COVID-19 continue to evolve, the decision of timing of intubation remains paramount. While non-invasive ventilation may allow for delaying intubation, it is possible that there are downstream effects of delayed intubation that should be considered.

Immunologic risk factors contribute to endothelial dysfunction and development of pulmonary vascular disease. Immune checkpoint inhibitors, used as immunotherapies for malignancies, have a wide range of reported immune-related adverse events. We retrospectively describe the impact of immune checkpoint inhibitors on the development of pulmonary vascular injury and right ventricular dysfunction as compared across both computed tomography and transthoracic echocardiography. Twenty-four of 389 patients treated with immune checkpoint inhibitors at a single academic center between 2015 and 2019 were evaluated. Thirteen (54%) patients were treated with anti-programmed cell death receptor 1 (PD-1), 8 (33%) with anti-programmed death receptor ligand 1 (PD-L1) therapy, and 3 (13%) with combination anti-PD-1 and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) therapy. At a median of 85 days of immune checkpoint inhibitor therapy, RVfwLS significantly increased from –20.6% to –16.7% ( p = 0.002). After a median of 59 days of immune checkpoint inhibitor therapy, median pulmonary artery to aorta ratio worsened from 0.83 to 0.89 ( p = 0.03). There was an correlation of duration of immune checkpoint inhibitor therapy (β = –0.574, p = 0.003) with percent change in RVfwLS. Patients who received anti-PD-1 therapy (β = –0.796, p = 0.001) showed the greatest correlation of duration of immune checkpoint inhibitor therapy with percent change in RVfwLS. Exposure to immune checkpoint inhibitors are associated with RV dysfunction and vascular changes as measured by strain and computed tomography, respectively.

Tocilizumab, an interleukin-6 receptor antagonist, has been used to treat critically ill patients with coronavirus disease-2019. We present the case of a previously immunocompetent man with coronavirus disease-2019 who developed invasive pulmonary aspergillosis after treatment with tocilizumab, illustrating the importance of considering opportunistic infections when providing immune modulating therapy.

Pulmonary embolism is associated with high rates of mortality and morbidity. It is important to understand direct comparisons of current interventions to differentiate favorable outcomes and complications. The objective of this study was to compare ultrasound-accelerated thrombolysis versus systemic thrombolysis versus anticoagulation alone and their effect on left ventricular outflow tract velocity time integral. This was a retrospective cohort study of subjects ≥18 years of age with a diagnosis of submassive or massive pulmonary embolism. The primary outcome was the percent change in left ventricular outflow tract velocity time integral between pre- and post-treatment echocardiograms. Ultrasound-accelerated thrombolysis compared to anticoagulation had a greater improvement in left ventricular outflow tract velocity time integral, measured by percent change. No significant change was noted between the ultrasound-accelerated thrombolysis and systemic thrombolysis nor systemic thrombolysis and anticoagulation groups. Pulmonary artery systolic pressure only showed a significant reduction in the ultrasound-accelerated thrombolysis versus anticoagulation group. The percent change of right ventricular to left ventricular ratios was improved when systemic thrombolysis was compared to both ultrasound-accelerated thrombolysis and anticoagulation. In this retrospective study of submassive or massive pulmonary embolisms, left ventricular outflow tract velocity time integral demonstrated greater improvement in patients treated with ultrasound-accelerated thrombolysis as compared to anticoagulation alone, a finding not seen with systemic thrombolysis. While this improvement in left ventricular outflow tract velocity time integral parallels the trend seen in mortality outcomes across the three groups, it only correlates with changes seen in pulmonary artery systolic pressure, not in other markers of echocardiographic right ventricular dysfunction (tricuspid annular plane systolic excursion and right ventricular to left ventricular ratios). Changes in left ventricular outflow tract velocity time integral, rather than echocardiographic markers of right ventricular dysfunction, may be considered a more useful prognostic marker of both dysfunction and improvement after reperfusion therapy.

We describe a male patient who presents 2 years posttransplant with cough and dyspnea. A negative pulmonary workup led to an endomyocardial biopsy and the diagnosis of cytomegalovirus (CMV) myocarditis. The patient was treated with ganciclovir and intravenous immunoglobulin. This illustrates a very late presentation of posttransplant CMV myocarditis and the usefulness of myocardial biopsy in diagnosis of CMV carditis.

Interstitial lung disease (ILD) is an inflammatory and fibrotic infiltrative process of the lung that is often associated with collagen vascular disease in women. Untreated, it results in collagen deposition in the lung interstitium that can lead to a slow suffocating death. Pregnancy planning is often not discussed with women who have ILD due to concerns about potentially aggravating the disease process, or due to lack of knowledge about the safety of medications used to treat ILD. With improved understanding of the pathophysiology of both autoimmune disease and ILD, it has become clear that safe, planned pregnancies are possible in most women with ILD. In this article, our aim is to review diagnosis, treatment, and disease course of ILD in women who are planning a pregnancy or are pregnant. Better understanding of the disease process and knowledge of safe treatments will likely lead to improved pregnancy planning in women with ILD.