Screening for Incidental Sars-Cov-2 Infection in a Neurocritical Care Unit: A Longitudinal Diagnostic Prediction Model

Background: Rapid diagnosis of SARS-CoV-2 infection in patients not primarily assigned with the diagnosis of COVID-19 is highly relevant to effectively rule out virus transmission among patients and medical staff. The purpose is to develop a model for the prediction of the actual presence of a SARS-CoV-2 infection before a valid test result is available and to avoid unnecessary testing in Critical Care Units. Methods: Datasets of laboratory and blood gas analysis tests were collected retrospectively for the development and subsequent validation of machine learning (ML) based models. The data set was composed of 1. 254 SARS-CoV-2 positive cases, collected in an ICU dedicated to patients with COVID-19 pneumonia, 2a. 914 SARS-CoV-2 negative patients treated in a Neurocritical Care Unit and 2b. 32 patients treated for severe influenza pneumonia in a Medical ICU at the same hospital. The models were subsequently validated on a dataset collected from the Neurocritical Care Unit that consisted of data from 7 positive and 42 negative patients. Models were adapted to newly available laboratory values throughout their ICU stay. Extremely Randomized Trees (ERT) and Random Forest (RF) models were evaluated. A baseline model comprising fully grown trees, an optimized model including optimal values for the maximum depth, and a simplified model that only uses the 6 most important features were trained. Results: The overall best model, evaluated via crossvalidation on the development set, is an optimized ERT model with a ROC AUC value of 0.946. The model performance on the validation set is best for the simplified RF model achieving a ROC AUC value of 0.701. Gini feature and permutation importance for the simplified RF model revealed hemoglobin, procalcitonin, C-reactive protein, glomerular filtration rate based on CKD-EPI equation, creatinine, and urea as the most important input features. Using the simplified RF model and a threshold of 0.012 for the probability, a sensitivity above 80% with a specificity of 43% is achieved. Compared to a hypothetical daily testing regimen, using a threshold of 0.145, the simplified RF model detects all positive cases, and, with a false positive rate of 35%, daily tests might be reduced by two thirds. Conclusions: The model developed may support the medical staff in the ICUs by enabling faster and more reliable recognition of COVID-19. Unnecessary serial test sampling might be reduced. To ensure the quality of the model before clinical use, it should be further validated in prospective patient cohorts

Factors associated with death and limitation of life-sustaining therapies in patients with traumatic brain injury

Aim of the Study: A substantial proportion of deaths of patients in the Intensive Care Unit (ICU) follow a decision to limit life-sustaining therapies. Patients with moderate to severe Traumatic Brain Injury (TBI) differ from the general ICU population: They are usually younger, previously healthy, and often with no advance directives. The objective of this study was to identify factors associated with mortality and limitation of life-sustaining therapies in patients with moderate to severe traumatic brain injury in a Swiss academic tertiary care hospital. Methods: This study was a retrospective single center analysis of 170 non-elective admissions to the surgical ICU of a Swiss academic tertiary care hospital over a three-year period. Patients were eligible for the study if diagnosed with moderate to severe blunt TBI, and if the ICU length of stay was at least 48 hrs. Factors associated with mortality were investigated. Results: Mean age was 48 ± 21 years, 72.3% were male, and pre-existing medical conditions were overall rare. Forty-five patients (26.5%) died within 6 months after TBI (Non-survivors group). Most deaths (n=43, 95.5%) occurred after limitation of life-sustaining therapies. In the multiple binary logistic regression model age, Protestant religion, hypoxemia during the rescue phase, a higher category in the Marshall classification and a higher Injury Severity Score were independently associated with death. Conclusion: At our institution, most deaths of patients with moderate to severe TBI occurred after a deliberate decision to limit life-sustaining therapies. This decision was associated with age, spiritual belief of the patient, hypoxemia in the pre-hospital setting, radiological findings, and severity scores. Written advance directives should be encouraged to help surrogate decision makers and physicians in the acute and sudden setting of TBI to respect the patient’s willed

Factors associated with intravenous lidocaine in pediatric patients undergoing laparoscopic appendectomy – a retrospective, single-centre experience

Abstract Background Due to its potential beneficial effects, intra- and postoperative application of intravenous lidocaine has become increasingly accepted over the last couple of years, e.g. in patients undergoing laparoscopic surgical procedures. Based on its beneficial properties, lidocaine was introduced to the standard of care for all pediatric laparoscopic procedures in our institution in mid-2016. In contrast to adult care, scarce data is available regarding the use of perioperative intravenous lidocaine administration in children undergoing laparoscopic procedures, such as an appendectomy. Methods Retrospective analysis of all pediatric patients undergoing laparoscopic appendectomy at the University Children’s Hospital Zurich in 2016. Perioperative data, as recorded in the electronic patient data management system, were evaluated for any signs of systemic lidocaine toxicity (neurological and cardiovascular), behavioral deterioration, as well as for hemodynamic instability. Additionally, the incidence of postoperative nausea and vomiting, administration of pain rescue medication, time to hospital discharge and to first bowel movement, as well as any postoperative complications were recorded. Starting on 01/07/2016, all patients undergoing laparoscopic surgery received intravenous lidocaine (1.5 mg/kg body weight (BW) bolus after induction of anesthesia followed by continuous infusion of 1.5 mg/kgBW/h). These patients were then compared to children without lidocaine administration who had undergone laparoscopic appendectomy between 01/01/2016 and 30/06/2016. Results Data of 116 patients was analyzed. Of these, 60 patients received lidocaine. No signs of systemic toxicity, neurologic impairment or circulatory disturbances were noted in any of these patients. A (non-significant) difference in the incidence of emergence delirium was observed (0 cases in the lidocaine group vs. 4 cases in the control group, p = 0.05). Conclusion This retrospective analysis did not reveal any adverse effects in pediatric patients receiving intravenous lidocaine for laparoscopic appendectomy under general anesthesia. However, further trials investigating beneficial effects as well as pharmacokinetic properties of intravenous lidocaine in children are required

Quantifying Variation in Bacterial Reproductive Fitness: a High-Throughput Method

To evaluate changes in reproductive fitness of bacteria, e.g., after acquisition of antimicrobial resistance, a low-cost high-throughput method to analyze bacterial growth on agar is desirable for broad usability. In our bacterial quantitative fitness analysis (BaQFA), arrayed cultures are spotted on agar and photographed sequentially while growing. These time-lapse images are analyzed using a purpose-built open-source software to derive normalized image intensity (NI) values for each culture spot. Subsequently, a Gompertz growth model is fitted to NI values, and fitness is calculated from model parameters. To represent a range of clinically important pathogenic bacteria, we used different strains of Enterococcus faecium, Escherichia coli, and Staphylococcus aureus, with and without antimicrobial resistance. Relative competitive fitness (RCF) was defined as the mean fitness ratio of two strains growing competitively on one plate.BaQFA permitted the accurate construction of growth curves from bacteria grown on semisolid agar plates and fitting of Gompertz models. Normalized image intensity values showed a strong association with the total CFU/ml count per spotted culture (P < 0.001) for all strains of the three species. BaQFA showed relevant reproductive fitness differences between individual strains, suggesting substantially higher fitness of methicillin-resistant S. aureus JE2 than Cowan (RCF, 1.58; P < 0.001). Similarly, the vancomycin-resistant E. faecium ST172b showed higher competitive fitness than susceptible E. faecium ST172 (RCF, 1.59; P < 0.001). Our BaQFA method allows detection of fitness differences between bacterial strains and may help to estimate epidemiological antimicrobial persistence or contribute to the prediction of clinical outcomes in severe infections.IMPORTANCE Reproductive fitness of bacteria is a major factor in the evolution and persistence of antimicrobial resistance and may play an important role in severe infections. With a computational approach to quantify fitness in bacteria growing competitively on agar plates, our high-throughput method has been designed to obtain additional phenotypic data for antimicrobial resistance analysis at a low cost. Furthermore, our bacterial quantitative fitness analysis (BaQFA) enables the investigation of a link between bacterial fitness and clinical outcomes in severe invasive bacterial infections. This may allow future use of our method for patient management and risk stratification of clinical outcomes. Our proposed method uses open-source software and a hardware setup that can utilize consumer electronics. This will enable a wider community of researchers, including those from low-resource countries, where the burden of antimicrobial resistance is highest, to obtain valuable information about emerging bacterial strains

Quantifying Variation in Bacterial Reproductive Fitness: a High-Throughput Method.

To evaluate changes in reproductive fitness of bacteria, e.g., after acquisition of antimicrobial resistance, a low-cost high-throughput method to analyze bacterial growth on agar is desirable for broad usability. In our bacterial quantitative fitness analysis (BaQFA), arrayed cultures are spotted on agar and photographed sequentially while growing. These time-lapse images are analyzed using a purpose-built open-source software to derive normalized image intensity (NI) values for each culture spot. Subsequently, a Gompertz growth model is fitted to NI values, and fitness is calculated from model parameters. To represent a range of clinically important pathogenic bacteria, we used different strains of Enterococcus faecium, Escherichia coli, and Staphylococcus aureus, with and without antimicrobial resistance. Relative competitive fitness (RCF) was defined as the mean fitness ratio of two strains growing competitively on one plate.BaQFA permitted the accurate construction of growth curves from bacteria grown on semisolid agar plates and fitting of Gompertz models. Normalized image intensity values showed a strong association with the total CFU/ml count per spotted culture (P < 0.001) for all strains of the three species. BaQFA showed relevant reproductive fitness differences between individual strains, suggesting substantially higher fitness of methicillin-resistant S. aureus JE2 than Cowan (RCF, 1.58; P < 0.001). Similarly, the vancomycin-resistant E. faecium ST172b showed higher competitive fitness than susceptible E. faecium ST172 (RCF, 1.59; P < 0.001). Our BaQFA method allows detection of fitness differences between bacterial strains and may help to estimate epidemiological antimicrobial persistence or contribute to the prediction of clinical outcomes in severe infections.IMPORTANCE Reproductive fitness of bacteria is a major factor in the evolution and persistence of antimicrobial resistance and may play an important role in severe infections. With a computational approach to quantify fitness in bacteria growing competitively on agar plates, our high-throughput method has been designed to obtain additional phenotypic data for antimicrobial resistance analysis at a low cost. Furthermore, our bacterial quantitative fitness analysis (BaQFA) enables the investigation of a link between bacterial fitness and clinical outcomes in severe invasive bacterial infections. This may allow future use of our method for patient management and risk stratification of clinical outcomes. Our proposed method uses open-source software and a hardware setup that can utilize consumer electronics. This will enable a wider community of researchers, including those from low-resource countries, where the burden of antimicrobial resistance is highest, to obtain valuable information about emerging bacterial strains

Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies

BACKGROUND Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), our approach focused on antiphospholipid antibodies (aPL). METHODS In this retrospective cohort study clinical data and aPL from 64 patients with COVID-19 were compared from three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 2020. RESULTS Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID) (41%), a discovery cohort with severe illness (sdCOVID) (22%) and a confirmation cohort with severe illness (scCOVID) (38%). Total IgA, IgG and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity

Erratum to: Severe Coronavirus Disease 2019 (COVID-19) is Associated With Elevated Serum Immunoglobulin (Ig) A and Antiphospholipid IgA Antibodies

BACKGROUND Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), our approach focused on antiphospholipid antibodies (aPL). METHODS In this retrospective cohort study clinical data and aPL from 64 patients with COVID-19 were compared from three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 2020. RESULTS Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID) (41%), a discovery cohort with severe illness (sdCOVID) (22%) and a confirmation cohort with severe illness (scCOVID) (38%). Total IgA, IgG and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity