Functional differences between human NKp44- and NKp44+ RORC+ innate lymphoid cells

Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC+ innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC+ innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44+ IL-22 producing cells are present in tonsils while NKp44- IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44+ ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44+ ILC are the main ILC subset producing IL-22. NKp44- ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Diagnostic accuracy of 64 slice multidetector coronary computed tomographic angiography in left ventricular systolic dysfunction

Detecting coronary artery disease (CAD) is pivotal in etiologic assessment and management of left ventricular (LV) systolic dysfunction. Only a limited number of studies have specifically addressed the accuracy of coronary computed tomographic angiography (CCTA) in detection/exclusion of CAD in patients with LV systolic dysfunction. We included patients who were referred for CCTA and invasive coronary angiography within 6 months of each other because of chest pain, either as part of clinical work-up in two Los Angeles medical centers from September 2006 to May 2010 or as part of the multicenter ACCURACY trial. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of 64 slice multidetector CCTA against coronary angiography were calculated. Five hundred and thirty-seven patients were included: 228 (42.5%) were women, mean age was 62 ± 12 years, 82 (15.3%) had LV systolic dysfunction (defined by LVEF < 50%). On a patient-based model, the sensitivity of CCTA to detect 50% and 70% coronary lesions was excellent across all LVEF-derived cohorts, ranging from 92% to 100%. The negative predictive value was similarly excellent, ranging from 88% to 100%. CCTA was fairly specific for CAD, with specificity ranging from 83% to 93%, and positive predictive value from 81% to 92%. There was no significant between-group difference for any of the accuracy measures for detecting coronary stenosis at 50% or 70% cutoff. Sixty-four slice multidetector CCTA is a very sensitive and fairly specific noninvasive diagnostic procedure for detecting coronary stenosis in patients with chest pain regardless of LV systolic function at presentation

Bronchoalveolar Lung Carcinoma Manifesting Itself as a Swinging Heart

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Diagnostic accuracy of 64 slice multidetector coronary computed tomographic angiography in left ventricular systolic dysfunction.

BackgroundDetecting coronary artery disease (CAD) is pivotal in etiologic assessment and management of left ventricular (LV) systolic dysfunction. Only a limited number of studies have specifically addressed the accuracy of coronary computed tomographic angiography (CCTA) in detection/exclusion of CAD in patients with LV systolic dysfunction.MethodsWe included patients who were referred for CCTA and invasive coronary angiography within 6 months of each other because of chest pain, either as part of clinical work-up in two Los Angeles medical centers from September 2006 to May 2010 or as part of the multicenter ACCURACY trial. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of 64 slice multidetector CCTA against coronary angiography were calculated.ResultsFive hundred and thirty-seven patients were included: 228 (42.5%) were women, mean age was 62 ± 12 years, 82 (15.3%) had LV systolic dysfunction (defined by LVEF &lt; 50%). On a patient-based model, the sensitivity of CCTA to detect 50% and 70% coronary lesions was excellent across all LVEF-derived cohorts, ranging from 92% to 100%. The negative predictive value was similarly excellent, ranging from 88% to 100%. CCTA was fairly specific for CAD, with specificity ranging from 83% to 93%, and positive predictive value from 81% to 92%. There was no significant between-group difference for any of the accuracy measures for detecting coronary stenosis at 50% or 70% cutoff.ConclusionSixty-four slice multidetector CCTA is a very sensitive and fairly specific noninvasive diagnostic procedure for detecting coronary stenosis in patients with chest pain regardless of LV systolic function at presentation

Diagnostic accuracy of 64 slice multidetector coronary computed tomographic angiography in left ventricular systolic dysfunction

Background: Detecting coronary artery disease (CAD) is pivotal in etiologic assessment and management of left ventricular (LV) systolic dysfunction. Only a limited number of studies have specifically addressed the accuracy of coronary computed tomographic angiography (CCTA) in detection/exclusion of CAD in patients with LV systolic dysfunction. Methods: We included patients who were referred for CCTA and invasive coronary angiography within 6 months of each other because of chest pain, either as part of clinical work-up in two Los Angeles medical centers from September 2006 to May 2010 or as part of the multicenter ACCURACY trial. Sensitivity, specificity, positive and negative predictive value, and likelihood ratios of 64 slice multidetector CCTA against coronary angiography were calculated. Results: Five hundred and thirty-seven patients were included: 228 (42.5%) were women, mean age was 62 ± 12 years, 82 (15.3%) had LV systolic dysfunction (defined by LVEF <50%). On a patient-based model, the sensitivity of CCTA to detect 50% and 70% coronary lesions was excellent across all LVEF-derived cohorts, ranging from 92% to 100%. The negative predictive value was similarly excellent, ranging from 88% to 100%. CCTA was fairly specific for CAD, with specificity ranging from 83% to 93%, and positive predictive value from 81% to 92%. There was no significant between-group difference for any of the accuracy measures for detecting coronary stenosis at 50% or 70% cutoff. Conclusion: Sixty-four slice multidetector CCTA is a very sensitive and fairly specific noninvasive diagnostic procedure for detecting coronary stenosis in patients with chest pain regardless of LV systolic function at presentation