Balancing Cost and Efficiency in Screening Potential Organ Donors With Whole Body CT

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Exposure to intravenous posaconazole in critically ill patients with influenza : a pharmacokinetic analysis of the POSA‐FLU study

Background Data on posaconazole in the critically ill are scarce. In the POSA-FLU study, we examined the prevention of influenza-associated pulmonary aspergillosis with posaconazole in this population. Methods In this observational sub-study, we performed a pharmacokinetic analysis, including protein binding and target attainment (TA). Blood samples were collected over a 24 h-dosing interval on both an early (Day 2 or 3) and a later (>= Day 4) treatment day. Results Target attainment was shown for AUC(0-24) and C-min prophylaxis but not for C-min treatment. Moreover, a saturable protein binding with a significant, positive relationship between albumin concentrations and the maximum binding capacity was observed. Conclusions Our analysis indicates that posaconazole may be a suitable drug to further investigate for prophylaxis, as TA for prophylaxis was reached. Exposure targets for treatment were insufficiently attained in this population

Acute kidney injury in critical COVID-19 : a multicenter cohort analysis in seven large hospitals in Belgium

Background Acute kidney injury (AKI) has been reported as a frequent complication of critical COVID-19. We aimed to evaluate the occurrence of AKI and use of kidney replacement therapy (KRT) in critical COVID-19, to assess patient and kidney outcomes and risk factors for AKI and differences in outcome when the diagnosis of AKI is based on urine output (UO) or on serum creatinine (sCr). Methods Multicenter, retrospective cohort analysis of patients with critical COVID-19 in seven large hospitals in Belgium. AKI was defined according to KDIGO within 21 days after ICU admission. Multivariable logistic regression analysis was used to explore the risk factors for developing AKI and to assess the association between AKI and ICU mortality. Results Of 1286 patients, 85.1% had AKI, and KRT was used in 9.8%. Older age, obesity, a higher APACHE II score and use of mechanical ventilation at day 1 of ICU stay were associated with an increased risk for AKI. After multivariable adjustment, all AKI stages were associated with ICU mortality. AKI was based on sCr in 40.1% and UO in 81.5% of patients. All AKI stages based on sCr and AKI stage 3 based on UO were associated with ICU mortality. Persistent AKI was present in 88.6% and acute kidney disease (AKD) in 87.6%. Rapid reversal of AKI yielded a better prognosis compared to persistent AKI and AKD. Kidney recovery was observed in 47.4% of surviving AKI patients. Conclusions Over 80% of critically ill COVID-19 patients had AKI. This was driven by the high occurrence rate of AKI defined by UO criteria. All AKI stages were associated with mortality (NCT04997915)

Successful double-lung transplantation from a donor previously infected with SARS-CoV-2

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Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study.

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers

Multinational Observational Cohort Study of COVID-19-Associated Pulmonary Aspergillosis(1)

International audienceWe performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%

Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial

PURPOSE: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA. METHODS: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population). RESULTS: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment. CONCLUSION: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU