Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Circulating dipeptidyl peptidase 3 and bio-adrenomedullin levels are associated with impaired outcomes in critically ill COVID-19 patients: a prospective international multicentre study

INTRODUCTION: Dipeptidyl-peptidase-3 (DPP3) is a protease involved in the degradation of several cardiovascular mediators. Adrenomedullin (bio-ADM) is a peptide essential for regulation of endothelial barrier function. In different shock-pathologies, both biomarkers are associated with disease-severity, organ dysfunction and mortality. Associations with outcome in critically ill COVID-19 patients are unknown. OBJECTIVES: To investigate associations of bio-ADM and cDPP3 with short-term outcome in critically ill COVID-19 patients (n=80). METHODS: Multicenter prospective cohort study. Primary endpoint was 28-day mortality. Secondary endpoints included different severities of acute kidney injury (AKI). RESULTS: cDPP3 levels were mainly associated with 28-day mortality; AUROC's of 0.69 (0.56–0.82, p=0.023), 0.77 (0.64–0.90, p<0.001) and 0.81 (0.65–0.96, p<0.001) at admission, day 3 and day 7, respectively. In contrast, bio-ADM levels were mainly associated with AKI: AUROC's of 0.64 (0.51–0.77, p=0.048), 0.75 (0.64–0.86, p<0.001) and 0.83 (0.74–0.93, p<0.001) for day 1, 3 and 7, respectively. Interestingly, patients with high levels of both cDPP3 and bio-ADM at day 7 had an additionally increased risk of 28-day-mortality; HR 11.8 (2.5–55.3, p<0.001). CONCLUSIONS: cDPP3 and bio-ADM responses were associated with short-term mortality and AKI in critically ill COVID-19 patients, respectively. These findings suggest that treatment with specific antibodies modulating cDPP3 or bio-ADM related pathways may improve outcome of COVID-19

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

International audienceDiagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients (n = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (Af-qPCR), and galactomannan testing were performed on all respiratory samples (n = 350). Serum galactomannan, β-d-glucan, and plasma Af-qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test, P = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) (P < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately

Combination of Mycological Criteria: a Better Surrogate to Identify COVID-19-Associated Pulmonary Aspergillosis Patients and Evaluate Prognosis?

International audienceDiagnosis of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remains unclear especially in nonimmunocompromised patients. The aim of this study was to evaluate seven mycological criteria and their combination in a large homogenous cohort of patients. All successive patients (n = 176) hospitalized for COVID-19 requiring mechanical ventilation and who clinically worsened despite appropriate standard of care were included over a 1-year period. Direct examination, culture, Aspergillus quantitative PCR (Af-qPCR), and galactomannan testing were performed on all respiratory samples (n = 350). Serum galactomannan, β-d-glucan, and plasma Af-qPCR were also assessed. The criteria were analyzed alone or in combination in relation to mortality rate. Mortality was significantly different in patients with 0, ≤2, and ≥3 positive criteria (log rank test, P = 0.04) with death rate of 43.1, 58.1, and 76.4%, respectively. Direct examination, plasma qPCR, and serum galactomannan were associated with a 100% mortality rate. Bronchoalveolar lavage (BAL) galactomannan and positive respiratory sample culture were often found as isolated markers (28.1 and 34.1%) and poorly repeatable when a second sample was obtained. Aspergillus DNA was detected in 13.1% of samples (46 of 350) with significantly lower quantitative cycle (Cq) when associated with at least one other criterion (30.2 versus 35.8) (P < 0.001). A combination of markers and/or blood biomarkers and/or direct respiratory sample examination seems more likely to identify patients with CAPA. Af-qPCR may help identifying false-positive results of BAL galactomannan testing and culture on respiratory samples while quantifying fungal burden accurately

Etomidate has no effect on hypoxia reoxygenation and hypoxic preconditioning in isolated human right atrial myocardium

BACKGROUND: We examined the effects of etomidate on recovery of contractile function after hypoxia reoxygenation and hypoxic preconditioning in vitro using isolated human myocardium. METHODS: Human right atrial myocardium were obtained at the time of cardiac surgery from 38 adults patients. We recorded isometric force of contraction (FoC) of atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation (HR). In separate groups, muscles were exposed to etomidate (10(-7), 10(-6), 10(-5) M) 10 min before and throughout the HR periods. Hypoxic preconditioning was induced by 4-min hypoxia followed by 7-min reoxygenation applied before HR periods. Etomidate 10(-5) M was administered before, throughout, and after the hypoxic preconditioning stimulus. Recovery of FoC (expressed as % of baseline value) at the end of HR was compared among groups. RESULTS: Compared with the control group (FoC: 52%+/-10%), etomidate 10(-7) M (FoC: 57%+/-9%; P=0.24), 10(-6) M (FoC: 61%+/-11%; P=0.10), and 10(-5) M (FoC: 54%+/-9%; P=0.29) did not modify the recovery of FoC after HR. Hypoxic preconditioning-induced increase in the recovery of FoC (87%+/-5%; P<0.001 vs control group) was not modified in the presence of etomidate 10(-5) M (FoC: 86%+/-7%; P=0.74 vs hypoxic preconditioning group). CONCLUSIONS: Etomidate did not modify the in vitro FoC of human myocardium exposed to HR. Furthermore, etomidate did not modify the protective effect of hypoxic preconditioning

Risk factors associated with Covid-19-associated pulmonary aspergillosis in ICU patients: a French multicentric retrospective cohort

International audienceObjectivesThe main objective of this study was to determine invasive pulmonary aspergillosis (IPA) incidence in the COVID-19 patients admitted to the intensive care unit (ICU), describe the patient characteristics associated with its occurrence and evaluate the impact on prognosis.MethodsWe conducted a retrospective cohort study including all successive COVID-19 patients hospitalized in four ICUs with secondary deterioration and ≥1 respiratory sample sent to the mycology department. A strengthened IPA testing strategy including seven mycological criteria was used. Patients were classified as probable IPA according to the EORTC/MSGERC classification if immunocompromised and to the recent COVID-19-associated IPA classification otherwise.ResultsProbable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio, 3.1; 95%-confidence interval, 1.1-8.5; p=0.02). A trend was observed with high dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% vs. 32/87, 36.8%; p<0.01).ConclusionIPA is a relatively frequent complication in severe COVID-19 patients responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient susceptibility to IPA