Severe Toxic Epidermal Necrolysis and Drug Reaction with Eosinophilia and Systemic Symptoms Overlap Syndrome Treated with Benralizumab: A Case Report

TEN/DRESS overlap syndrome can be difficult to diagnose, especially if it is masked by comorbidities in critically ill patients in intensive care units. The existing therapy for the two conditions is also a major challenge for the treating team. A possible alternative, especially for refractory cases, is benralizumab as an IL-5-receptor alpha-chain-specific humanized monoclonal antibody (IgG1k). We are able to show a successful treatment in this case report

Eye-tracking to observe compliance with hand hygiene in the intensive care unit – a randomised feasibility study

Background: Healthcare-associated infections are associated with increased patient mortality. Hand hygiene is the most effective method to reduce these infections. Despite simplification of this easy intervention, compliance with hand disinfection remains low. Current assessment of hand hygiene is mainly based on observation by hygiene specialists. The aim of this study was to investigate additional benefits of eye-tracking during the analysis of hand hygiene compliance of healthcare professionals in the intensive care unit. Methods: In a simulated, randomised cross-over study conducted at the interdisciplinary intensive care unit of the University Hospital Zurich (Switzerland), doctors and nurses underwent eye-tracking and completed two everyday tasks (injection of 10 micrograms of norepinephrine via a central venous line, blood removal from the central line) in two scenarios where alcoholic dispenser locations differed ("in-sight" and "out-of-sight"). The primary outcomes were dwell time, revisits, first fixation duration and average fixation time on three areas of interest (central venous line, alcohol dispenser, protective glove box) for both scenarios. Compliance with hand hygiene guidelines was analysed. Findings: 49 participants (35 nurses, 14 doctors) were included. Eye-tracking provided additional useful information compared to conventional observations. Dwell time, revisits, first fixation duration and average fixation time did not differ between the two scenarios for all areas of interest. Overall compliance with recommended hand hygiene measures was low in both doctors (mean 20%) and nurses (mean 42.9%). Conclusion: Compared to conventional observations offered additional helpful insights and provided an in-depth analysis of gaze patterns during the recording of hand hygiene compliance in the intensive care unit. Keywords: compliance; eye-tracking; hand hygiene; intensive care unit

The importance of post marketing quality control

BACKGROUND A previously published study reported on the nonlinear behaviour for airway pressure and tidal volume of the adjustable pressure-limiting (APL) valve of the Aisys CS2 anaesthesia machine (GE Healthcare, Madison, Wisconsin, USA) during manual bag ventilation. In co-operation with the manufacturer, an adapted APL valve was developed. OBJECTIVE To test and characterise the performance of an adapted APL valve and assess its clinical usability. DESIGN Two-stage study, consisting of an in-vitro testing of an adapted APL valve in a baby and adolescent lung model, followed by a clinical experience survey of anaesthesia personnel after the official implementation of the new APL valve into clinical routine. SETTING Anaesthesia Department at the University Children's Hospital Zurich. MAIN OUTCOME MEASURES Airway pressures and inspiratory tidal volumes during opening and closure of the APL valve at different settings. Likert scale assessment of performance expectance, effort expectance, behavioural intention and safety of the APL valve during clinical use. RESULTS In contrast to the original APL valve of the GE Aisys CS2, the adapted APL valve showed a nearly linear increase in airway pressures as well as in the tidal volumes measured. Most importantly, the measured pressures never exceeded the set pressures. Based on the experimental findings, all original APL valves of the GE Aisys CS2 were replaced by the adapted APL valve. Two months later, an anonymised and standardised questionnaire was handed out to all employees working with the adapted APL valve. Analysis of the questionnaire indicated that the adapted APL valve is easier and more precise to handle in the daily routine than the original one. CONCLUSION The newly adapted APL valve for the GE Aisys CS2 has considerably improved its linearity at lower pressures and supports our institution's bag mask ventilation practices

Pulmonary Surfactant Proteins are Inhibited by IgA Autoantibodies in Severe COVID-19

Rationale: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome with fatal outcomes. Evidence suggests that dysregulated immune responses, including autoimmunity, are key pathogenic factors. Objectives: To assess whether IgA autoantibodies target lung-specific proteins and contribute to disease severity. Methods: We collected 147 blood, 9 lung tissue, and 36 bronchoalveolar lavage fluid samples from three tertiary hospitals in Switzerland and one in Germany. Severe COVID-19 was defined by the need to administer oxygen. We investigated the presence of IgA autoantibodies and their effects on pulmonary surfactant in COVID-19 using the following methods: immunofluorescence on tissue samples, immunoprecipitations followed by mass spectrometry on bronchoalveolar lavage fluid samples, enzyme-linked immunosorbent assays on blood samples, and surface tension measurements with medical surfactant. Measurements and main results: IgA autoantibodies targeting pulmonary surfactant proteins B and C were elevated in patients with severe COVID-19, but not in patients with influenza or bacterial pneumonia. Notably, pulmonary surfactant failed to reduce surface tension after incubation with either plasma or purified IgA from patients with severe COVID-19. Conclusions: Our data suggest that patients with severe COVID-19 harbor IgA against pulmonary surfactant proteins B and C and that these antibodies block the function of lung surfactant, potentially contributing to alveolar collapse and poor oxygenation. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Critically ill COVID-19 patients with neutralizing autoantibodies against type I interferons have increased risk of herpesvirus disease.

Autoantibodies neutralizing the antiviral action of type I interferons (IFNs) have been associated with predisposition to severe Coronavirus Disease 2019 (COVID-19). Here, we screened for such autoantibodies in 103 critically ill COVID-19 patients in a tertiary intensive care unit (ICU) in Switzerland. Eleven patients (10.7%), but no healthy donors, had neutralizing anti-IFNα or anti-IFNα/anti-IFNω IgG in plasma/serum, but anti-IFN IgM or IgA was rare. One patient had nonneutralizing anti-IFNα IgG. Strikingly, all patients with plasma anti-IFNα IgG also had anti-IFNα IgG in tracheobronchial secretions, identifying these autoantibodies at anatomical sites relevant for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Longitudinal analyses revealed patient heterogeneity in terms of increasing, decreasing, or stable anti-IFN IgG levels throughout the length of hospitalization. Notably, presence of anti-IFN autoantibodies in this critically ill COVID-19 cohort appeared to predict herpesvirus disease (caused by herpes simplex viruses types 1 and 2 (HSV-1/-2) and/or cytomegalovirus (CMV)), which has been linked to worse clinical outcomes. Indeed, all 7 tested COVID-19 patients with anti-IFN IgG in our cohort (100%) suffered from one or more herpesviruses, and analysis revealed that these patients were more likely to experience CMV than COVID-19 patients without anti-IFN autoantibodies, even when adjusting for age, gender, and systemic steroid treatment (odds ratio (OR) 7.28, 95% confidence interval (CI) 1.14 to 46.31, p = 0.036). As the IFN system deficiency caused by neutralizing anti-IFN autoantibodies likely directly and indirectly exacerbates the likelihood of latent herpesvirus reactivations in critically ill patients, early diagnosis of anti-IFN IgG could be rapidly used to inform risk-group stratification and treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04410263

The importance of intravenous immunoglobulin treatment in critically ill patients with necrotizing soft tissue infection: a retrospective cohort study.

BACKGROUND Necrotizing soft-tissue infections are infections with high mortality. The use of immunoglobulins within a combination therapy including broad-spectrum antibiotics has been debated. We assessed potential benefits of immunoglobulins and hypothesized that they were associated with a treatment benefit in a high-resource setting. METHODS Patients with necrotizing soft-tissue infection hospitalized in the tertiary intensive care unit of the University Hospital of Zurich, Switzerland, between 2008 and 2020 were included retrospectively. The association between immunoglobulin administration and in-hospital survival, intensive care unit length of stay, the incidences of acute renal failure, acute respiratory distress syndrome and septic shock were analyzed. RESULTS After adjustment for confounders, no difference for in-hospital survival (hazard ratio 2.20, 95% confidence interval [CI] 0.24-20.20, p = 0.5), intensive care unit length of stay (subhazard ratio [SHR] 0.90, CI 0.41-1.98, p = 0.8) and the development of acute respiratory distress syndrome (SHR 1.2, CI 0.36-4.03, p = 0.77) was observed in patients with or without immunoglobulin treatment. The Simplified Acute Physiology Score II, the risk of developing acute renal failure (SHR 2.86, CI 1.33-6.15, p = 0.01) and septic shock (SHR 1.86, CI 1.02-3.40, p = 0.04) was higher in patients treated with immunoglobulins, possibly reflecting a higher disease severity beyond measured confounders. CONCLUSIONS No clear evidence for a benefit of immunoglobulins in our cohort with consistent antibiotic use was found. Patients receiving immunoglobulins appeared more severely ill. Complementary to high treatment standards and appropriate antibiotics including beta lactams and protein synthesis inhibitors, immunoglobulins should be administered on a case-to-case basis, at least while more evidence from larger randomized controlled trials is missing

Bacterial but no SARS-CoV-2 contamination after terminal disinfection of tertiary care intensive care units treating COVID-19 patients

BACKGROUND In intensive care units (ICUs) treating patients with Coronavirus disease 2019 (COVID-19) invasive ventilation poses a high risk for aerosol and droplet formation. Surface contamination of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) or bacteria can result in nosocomial transmission. METHODS Two tertiary care COVID-19 intensive care units treating 53 patients for 870 patient days were sampled after terminal cleaning and preparation for regular use to treat non-COVID-19 patients. RESULTS A total of 176 swabs were sampled of defined locations covering both ICUs. No SARS-CoV-2 ribonucleic acid (RNA) was detected. Gram-negative bacterial contamination was mainly linked to sinks and siphons. Skin flora was isolated from most swabbed areas and Enterococcus faecium was detected on two keyboards. CONCLUSIONS After basic cleaning with standard disinfection measures no remaining SARS-CoV-2 RNA was detected. Bacterial contamination was low and mainly localised in sinks and siphons

Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms

Background: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. Methods: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. Results: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). Conclusion: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended. Keywords: Clinical prediction model; Long COVID; Prognostic factors; Stratified medicin