Comparison of four diagnostic criteria for invasive pulmonary aspergillosis-A diagnostic accuracy study in critically ill patients.

BACKGROUND: In the absence of lung biopsy, there are various algorithms for the diagnosis of invasive pulmonary aspergillosis (IPA) in critically ill patients that rely on clinical signs, underlying conditions, radiological features and mycology. The aim of the present study was to compare four diagnostic algorithms in their ability to differentiate between probable IPA (i.e., requiring treatment) and colonisation. METHODS: For this diagnostic accuracy study, we included a mixed ICU population with a positive Aspergillus culture from respiratory secretions and applied four different diagnostic algorithms to them. We compared agreement among the four algorithms. In a subgroup of patients with lung tissue histopathology available, we determined the sensitivity and specificity of the single algorithms. RESULTS: A total number of 684 critically ill patients (69% medical/31% surgical) were included between 2005 and 2020. Overall, 79% (n = 543) of patients fulfilled the criteria for probable IPA according to at least one diagnostic algorithm. Only 4% of patients (n = 29) fulfilled the criteria for probable IPA according to all four algorithms. Agreement among the four diagnostic criteria was low (Cohen's kappa 0.07-0.29). From 85 patients with histopathological examination of lung tissue, 40% (n = 34) had confirmed IPA. The new EORTC/MSGERC ICU working group criteria had high specificity (0.59 [0.41-0.75]) and sensitivity (0.73 [0.59-0.85]). CONCLUSIONS: In a cohort of mixed ICU patients, the agreement among four algorithms for the diagnosis of IPA was low. Although improved by the latest diagnostic criteria, the discrimination of invasive fungal infection from Aspergillus colonisation in critically ill patients remains challenging and requires further optimization.

High estradiol and low testosterone levels are associated with critical illness in male but not in female COVID-19 patients: a retrospective cohort study.

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.