Sonal Pannu

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018–2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0–0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00–1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT 03255057).

Clinical data demonstrate an increased predisposition to cardiovascular disease (CVD) following severe COVID-19 infection. This may be driven by a dysregulated immune response associated with severe disease. Monocytes and vascular tissue resident macrophages play a critical role in atherosclerosis, the main pathology leading to ischemic CVD. Natural killer (NK) cells are a heterogenous group of cells that are critical during viral pathogenesis and are known to be dysregulated during severe COVID-19 infection. Their role in atherosclerotic cardiovascular disease has recently been described. However, the contribution of their altered phenotypes to atherogenesis following severe COVID-19 infection is unknown. We demonstrate for the first time that during and after severe COVID-19, circulating proinflammatory monocytes and activated NK cells act synergistically to increase uptake of oxidized low-density lipoprotein (Ox-LDL) into vascular tissue with subsequent foam cell generation leading to atherogenesis despite recovery from acute infection. Our data provide new insights, revealing the roles of monocytes/macrophages, and NK cells in COVID-19-related atherogenesis.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS□CoV□ 2) is a highly pathogenic corona virus which causes COVID-19 and resulted in millions of deaths and led to a global public health emergency. An effective and appropriate immune response is essential to control and eliminate viral infections, however, dysregulated immune responses may lead to immunopathology in viral infections. Clinical data showed that COVID-19 may promote the development of cardiovascular disorders (CVDs). However, exact mechanism associated with CVDs in COVID-19 patients is currently unknown. Monocytes are one of the major immune cell subsets that contribute to host defense against many infections but also associated with immunopathology and development of CVDs. Thus, in this study we investigated the role of monocyte subsets in COVID-19 associated CVDs. By using high dimensional flowcytometry, immune biomarker assays and multi variant data analysis in healthy donors (n=17), severe-COVID-19 patients (n=20) (ICU) and COVID-19 recovered individuals (n=30), we found elevated intermediate monocytes and Monocyte chemoattractant protein-1, one of the most important chemokines that regulates migration and infiltration of monocytes to the subendothelial space, where they may become foam cells. Spearman correlation network analysis showed that strong correlation between increase intermediate monocytes in the whole blood and plasma cardimetabolic biomarkers such as fatty acid binding protein 4, C-reactive protein, soluble CD14 and LPS binding protein in ICU patients. Our data show for the first time that the possible role of monocytes in the development of CVDs in ICU patients.

Rationale: The nature, variability, and extent of early warning clinical practice alerts derived from automated query of electronic health records (e-alerts) currently used in acute care settings for clinical care or research is unknown. Objectives: To describe e-alerts in current use in acute care settings at medical centers participating in a nationwide critical care research network. Methods: We surveyed investigators at 38 institutions involved in the National Institutes of Health–funded Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) for quantitative and qualitative analysis. Measurements and Main Results: Thirty sites completed the survey (79% response rate). All sites used electronic health record systems. Epic Systems was used at 56% of sites; the others used alternate commercially available vendors or homegrown systems. Respondents at 57% of sites represented in this survey used e-alerts. All but 1 of these 17 sites used an e-alert for early detection of sepsis-related syndromes, and 35% used an e-alert for pneumonia. E-alerts were triggered by abnormal laboratory values (37%), vital signs (37%), or radiology reports (15%) and were used about equally for clinical decision support and research. Only 59% of sites with e-alerts have evaluated them either for accuracy or for validity. Conclusions: A majority of the research network sites participating in this survey use e-alerts for early notification of potential threats to hospitalized patients; however, there was significant variability in the nature of e-alerts between institutions. Use of one common electronic health record vendor at more than half of the participating sites suggests that it may be possible to standardize e-alerts across multiple sites in research networks, particularly among sites using the same medical record platform.