Plasminogen Degradation by Neutrophil Elastase in Pleural Infection, Not High Plasminogen Activator Inhibitor 1, Is the Cause of Intrapleural Lytic Failure.

BACKGROUND: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. RESEARCH QUESTION: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? STUDY DESIGN AND METHODS: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of 0.05. RESULTS: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. INTERPRETATION: Inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03583931; URL: www. CLINICALTRIALS: gov.

Glucocorticoid Therapy in COVID-19-Induced Organizing Pneumonia: A Rare Occurrence.

Background Although the incidence of post-COVID-19 organizing pneumonia (OP) is low, the mortality and morbidity in select patients appear to be high. Anticipating specific populations who may be at higher risk and initiating treatment earlier could reduce mortality. Research question Does treatment with high dose, standard dose, or no glucocorticoids for COVID-19 infection impact the incidence and clinical outcome in COVID-19-induced OP? Study design and methods This was a single-center, retrospective, observational cohort study conducted from 03/01/2020 to 06/30/2021 in hospitalized patients over the age of 18 with confirmed COVID-19 infection and computed tomography (CT) scan evidence of OP. Institutional review board (IRB) approval was obtained from the institution (STUDY00002241). Patients' demographics and oxygen requirements at the time of diagnosis, at the time of discharge, and at one, three, six, 10, and 12 months post-discharge were obtained. The dose, duration, and choice of glucocorticoid therapy were recorded for each subject, as well as oxygen requirements during hospitalization. Despite radiological evidence of OP, patients on minimal supplemental oxygen requirements did not receive high-dose or long-duration glucocorticoid therapy. Results A total of 881 patients were admitted with COVID-19, of which 42 met the study criteria. Three patients underwent a lung biopsy to confirm the diagnosis of organizing pneumonia. All other patients were diagnosed based on CT imaging and clinical presentation. Of the patients, 17% did not receive any steroid treatment, while 36% received dexamethasone and 43% received prednisone. The most common oxygen requirement at the time of discharge for steroid-treated patients was nasal cannula (55%) and room air (29%). The incidence of OP in this patient population was 0.05 with a mortality rate of 14%. Interpretation and relevance The incidence of post-COVID-19 OP appears to be lower than anticipated. Steroids for patients on lower supplemental oxygen requirements were discontinued although they had radiological evidence of OP. Patients who were on higher supplemental oxygen requirements at 10 days were continued on steroids regardless of imaging. The decision to continue steroids should be based on individual patient characteristics such as oxygen requirements. In the future, larger multicenter cohort studies would help understand further treatment of post-COVID-19-associated OP. Anticipating specific populations who may be at higher risk and starting treatment earlier could help reduce mortality.

Using Shared Medical Appointments for Delivering Patient-Centered Care to Cancer Survivors: A Feist-Weiller Cancer Center Pilot Study.

Background: Shared medical appointments (SMAs) have shown promise in the care of patients with conditions such as diabetes; however, the impact of lifestyle medicine-based SMAs on the overall health status of cancer survivors remains poorly understood. Materials and Methods: This cross-sectional survey of patients was conducted to study the impact of a unique lifestyle medicine-based survivorship program on cancer survivors. Results: A total of 64 patients were telephonically contacted for the survey, out of which 39 (60.9%) patients responded. All patients (39 of 39, 100%) found the program to be helpful in some way; 26 patients (66.7%) found SMAs to be significantly helpful, while 13 patients (33.3%) found SMAs as only somewhat helpful. The majority noted feeling a great sense of support (35 of 39, 89.7%), followed by improvement in appetite (21 of 39, 54%) and improvement in pain (14 of 39, 35.9%). All patients reported at least some improvement in subjective well-being (SWB); patients who attended >3 appointments reported significant/very significant improvement in SWB (P = .03). Conclusion: SMAs offer promise in the effective delivery of lifestyle medicine-focused care to cancer survivors. Further prospective studies are needed to validate these findings.