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Purpose Corticosteroids, in particular dexamethasone, are one of the primary treatment options for critically ill COVID-19 patients. However, there are a growing number of cases that involve COVID-19-associated pulmonary aspergillosis (CAPA), and it is unclear whether dexamethasone represents a risk factor for CAPA. Our aim was to investigate a possible association of the recommended dexamethasone therapy with a risk of CAPA. Methods We performed a study based on a cohort of COVID-19 patients treated in 2020 in our 13 intensive care units at Charité Universitätsmedizin Berlin. We used ECMM/ISHM criteria for the CAPA diagnosis and performed univariate and multivariable analyses of clinical parameters to identify risk factors that could result in a diagnosis of CAPA. Results Altogether, among the n  = 522 intensive care patients analyzed, n  = 47 (9%) patients developed CAPA. CAPA patients had a higher simplified acute physiology score (SAPS) (64 vs. 53, p  < 0.001) and higher levels of IL-6 (1,005 vs. 461, p  < 0.008). They more often had severe acute respiratory distress syndrome (ARDS) (60% vs. 41%, p  = 0.024), renal replacement therapy (60% vs. 41%, p  = 0.024), and they were more likely to die (64% vs. 48%, p  = 0.049). The multivariable analysis showed dexamethasone (OR 3.110, CI95 1.112–8.697) and SAPS (OR 1.063, CI95 1.028–1.098) to be independent risk factors for CAPA. Conclusion In our study, dexamethasone therapy as recommended for COVID-19 was associated with a significant three times increase in the risk of CAPA. Trial registration Registration number DRKS00024578, Date of registration March 3rd, 2021.

Computerized critical care information systems (CCIS) can have a range of positive to negative impacts on clinical care in ICUs and the job satisfaction of ICU staff. Key factors influencing these effects include the usability of the IT system and the level of training provided. Resistance to using the system may arise from users due to increased control imposed by the system and from insufficient participation in its development and configuration. The usability of CCIS, along with other important barriers such as co-determination, has not been thoroughly examined. The study investigates barriers to using CCIS and aims to provide actionable recommendations for manufacturing companies and hospitals to ensure the successful implementation and use of CCIS. It focuses on known usability factors while incorporating open feedback from current users to uncover new insights and identify additional usability factors not previously documented in the literature. We conducted 10 semistructured qualitative interviews with ICU staff (4 nurses and 6 doctors) from 3 ICUs at a large German university hospital. Each interview lasted 1 hour and focused on providing a collective assessment of the CCIS. The interviews were recorded, transcribed, and coded using MAXQDA and then analyzed through both deductive and inductive content structure methods. A total of 86 distinct usability issues were identified and categorized into 7 main groups and 23 subgroups. The most common usability issues were (1) unclear information presentation, especially for medication; (2) overly lengthy or small interaction steps in documentation; (3) missing or scattered information across sections; (4) redundant data entry requirements; and (5) slow system speed. Additionally, other challenges associated with system usage included training, co-determination, the perception of feeling constrained, adherence to standard operating procedures, and changes in processes. Participants in the study highlighted that the level of contentment with the system has a direct influence on their job satisfaction. CCIS usability greatly influences satisfaction with the information technology system. Enhancing CCIS usability requires ongoing user testing and transparent employee involvement. Adequate training and standard operating procedure implementation are crucial. Investing time and financial resources in organizational frameworks and feedback mechanisms is an imperative for the successful implementation of CCIS.

Background Mobilisation and exercise intervention in general are safe and feasible in critically ill patients. For patients requiring catecholamines, however, doses of norepinephrine safe for mobilisation in the intensive care unit (ICU) are not defined. This study aimed to describe mobilisation practice in our hospital and identify doses of norepinephrine that allowed a safe mobilisation. Methods We conducted a retrospective single-centre cohort study of 16 ICUs at a university hospital in Germany with patients admitted between March 2018 and November 2021. Data were collected from our patient data management system. We analysed the effect of norepinephrine on level (ICU Mobility Scale) and frequency (units per day) of mobilisation, early mobilisation (within 72 h of ICU admission), mortality, and rate of adverse events. Data were extracted from free-text mobilisation entries using supervised machine learning (support vector machine). Statistical analyses were done using (generalised) linear (mixed-effect) models, as well as chi-square tests and ANOVAs. Results A total of 12,462 patients were analysed in this study. They received a total of 59,415 mobilisation units. Of these patients, 842 (6.8%) received mobilisation under continuous norepinephrine administration. Norepinephrine administration was negatively associated with the frequency of mobilisation (adjusted difference -0.07 mobilisations per day; 95% CI − 0.09, − 0.05; p  ≤ 0.001) and early mobilisation (adjusted OR 0.83; 95% CI 0.76, 0.90; p  ≤ 0.001), while a higher norepinephrine dose corresponded to a lower chance to be mobilised out-of-bed (adjusted OR 0.01; 95% CI 0.00, 0.04; p  ≤ 0.001). Mobilisation with norepinephrine did not significantly affect mortality ( p  > 0.1). Higher compared to lower doses of norepinephrine did not lead to a significant increase in adverse events in our practice ( p  > 0.1). We identified that mobilisation was safe with up to 0.20 µg/kg/min norepinephrine for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0–1) mobilisation. Conclusions Mobilisation with norepinephrine can be done safely when considering the status of the patient and safety guidelines. We demonstrated that safe mobilisation was possible with norepinephrine doses up to 0.20 µg/kg/min for out-of-bed (IMS ≥ 2) and 0.33 µg/kg/min for in-bed (IMS 0–1) mobilisation.

The COVID-19 pandemic has posed a major challenge to healthcare systems globally. Millions of people have been infected, and millions of deaths have been reported worldwide. Glucocorticoids have attracted worldwide attention for their potential efficacy in the treatment of COVID-19. Various glucocorticoids with different dosages and treatment durations have been studied in patients with different severities, with a suitable dosage and treatment duration not yet defined. This study aimed to investigate whether in-hospital survival differs between critically ill patients treated with low-dose glucocorticoids, high-dose glucocorticoids or no glucocorticoids. All critically ill patients admitted to the intensive care unit of the Charité Hospital—Universitätsmedizin Berlin between February 2020 and December 2021 with COVID-19 pneumonia receiving supplemental oxygen were eligible to participate in this multicenter real-world data study. Patients were retrospectively assigned to one of three groups: the high corticosteroid dose (HighC) group (receiving 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), the low corticosteroid dose (LowC) group (receiving less than 6 mg parenteral dexamethasone or an equivalent corticosteroid dosage for ten days), or the no corticosteroid (NoC) group. Overall survival and risk effects were compared among groups within the total observation period, as well as at 35 days after the onset of COVID-19 symptoms. Adjusted multivariable Cox proportional hazard regression analysis was performed to compare the risk of death between the treatment groups. Out of 1561 critically ill COVID-19 patients, 1014 were included in the baseline analysis. In the survival study, 1009 patients were assigned to the NoC (n = 346), HighC (n = 552), or LowC group (n = 111). The baseline characteristics were balanced between groups, except for age, BMI, APACHE II score, SOFA and SAPS II. While the 35-day survival did not show any differences, a landmark analysis of the patients surviving beyond 35 days revealed differences between groups. The restricted mean survival time was 112 days in the LowC group [95% CI: 97 – 128], 133 days in the HighC group [95% CI: 124 – 141] and 144 days in the NoC group [95% CI: 121 – 167]. The multivariable-adjusted Cox proportional hazard analysis indicated that, regardless of age, sex, health status or invasive oxygenation, a low-dose treatment increased the hazard of death of critically ill COVID-19 patients by a factor of 2.09 ([95% CI: 0.99, 4.4], p  = 0.05) and a high-dose corticosteroid treatment increased the risk by a factor of 1.07 ([95% CI: 0.53, 2.15], p  = 0.85) compared to no treatment with glucocorticoids. The analysis reveals that corticosteroid treatment does not influence the survival of critically ill COVID-19 patients in the intensive care unit within 35 days. Our evaluations further suggest that regardless of ventilation status, the decision-making process for administering corticosteroid therapy should account for the individual severity of the illness.

Interleukin (IL)-6 and IL-1 blockade showed beneficial results in patients with severe COVID-19 pneumonia and evidence of cytokine release at the early disease stage. Here, we report outcomes of open-label therapy with a combination of blocking IL-6 with tocilizumab 8 mg/kg up to 800 mg and IL-1 receptor antagonist anakinra 100–300 mg over 3–5 days. Thirty-one adult patients with severe COVID-19 pneumonia and signs of cytokine release, mean age 54 (30–79) years, 5 female, 26 male, and mean symptom duration 6 (3–10) days were treated. Patients with more than 10 days of symptoms, evidence of bacterial infection/elevated procalcitonin and other severe lung diseases were excluded. Computed tomography (CT) scans of the lung were performed initially and after 1 month; inflammatory activity was assessed on a scale 0–25. Twenty-five patients survived without intubation and mechanical lung ventilation, two patients died. C-reactive protein decreased in 19/31 patients to normal ranges. The mean activity CT score decreased from 14 (8–20) to 6 (0–16, n = 16). In conclusion, most of our patients recovered fast and sustained, indicating that early interruption of cytokine release might be very effective in preventing patients from mechanical ventilation, death, and long-term damage.

Background Passive immunization against SARS-CoV-2 limits viral burden and death from COVID-19; however, it poses a theoretical risk of disease exacerbation through antibody-dependent enhancement (ADE). ADE after anti-SARS-CoV2 antibody treatment has not been reported, and therefore the potential risk and promoting factors remain unknown. Case presentation A 75-year-old female was admitted to the emergency room with recurrent, unexplained bruises and leukocytopenia, anemia, and thrombocytopenia. Evaluation of a bone marrow biopsy established the diagnosis of an acute promyelocytic leukemia (APL). SARS-CoV-2 RT-PCR testing of nasal and throat swabs on admission was negative. During the routine SARS-CoV-2 testing of inpatients, our patient tested positive for SARS-CoV-2 on day 14 after admission without typical COVID-19 symptoms. Due to disease- and therapy-related immunosuppression and advanced age conferring a high risk of progressing to severe COVID-19 , casirivimab and imdevimab were administered as a preemptive approach. The patient developed immune activation and cytokine release syndrome (CRS) occurring within four hours of preemptive anti-SARS-CoV2 antibody (casirivimab/imdevimab) infusion. Immune activation and CRS were evidenced by a rapid increase in serum cytokines (IL-6, TNFα, IL-8, IL-10), acute respiratory insufficiency, and progressive acute respiratory distress syndrome. Discussion and conclusion The temporal relationship between therapeutic antibody administration and the rapid laboratory, radiological, and clinical deterioration suggests that CRS was an antibody-related adverse event, potentially exacerbated by APL treatment-mediated differentiation of leukemic blasts and promyelocytes. This case highlights the need for careful assessment of life-threatening adverse events after passive SARS-CoV-2 immunization, especially in the clinical context of patients with complex immune and hematological landscapes.

Purpose CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22). There is limited clinical data on the effect of CS on the plasma concentrations of beta-lactams. We aimed to evaluate the statistical and clinical impact of CS in a post-filter CKRT-CS setting on the plasma concentrations of the antibiotics meropenem and piperacillin in critically ill patients. Methods Patients admitted to the intensive care unit (ICU) who received a prolonged infusion of piperacillin or meropenem with CS-combined CKRT were included in this retrospective analysis. TDM (therapeutic drug monitoring) plasma blood samples were collected at three different points. The differences in antibiotic concentrations between Pre, Intra, and Post were statistically compared to evaluate the total and isolated contributions of CKRT and CS to antibiotic removal. CS, CKRT and combined clearance (CL) values were calculated. The hypothesis was that the CS filter would have no clinically relevant impact on antibiotic levels. Results 207 TDM samples were taken from 24 critically ill patients requiring beta-lactam antibiotics. Among these, 129 were meropenem samples, and 78 were piperacillin samples. A decrease in both antibiotic levels was observed between Pre and Intra, and Pre and Post, and the median relative difference between was >15% (meropenem: Pre–Intra 34.8%, Pre–Post 35.8%; piperacillin: Pre–Intra 41.1%, Pre–Post 34.7%), indicating a statistically and clinically significant effect of CKRT on both antibiotic exposures. No significant difference was observed between Intra and Post indicating no clinically relevant drug removal via the CS filter. Changes in CL attributed to CS were minimal, with combined CL differing by ≤8.60% compared to CKRT clearance. Conclusion The application of CS does not appear to significantly affect plasma concentrations of meropenem and piperacillin in critically ill patients.

Emphysematous diseases of the abdomen are rare with an often inconspicuous presentation of symptoms and rapid lethal outcome if untreated. We report the first successfully treated case of Clostridium perfringens -associated emphysematous hepatitis. In the emergency room, a 79-year-old man presented with shortness of breath and deteriorated general condition since the morning of admission. Initial CT scans showed a small but rapidly expanding gas collection in liver segment 6. Emergency surgery with atypical liver resection was performed immediately. With early resection and prolonged administration of antibiotics in the presence of sepsis, the patient recovered successfully and was discharged 37 days after admission. As in our case, prompt diagnosis with early surgical treatment is crucial for the management of emphysematous hepatitis.