scholarly journals SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Clemens Gutmann ◽  
Kaloyan Takov ◽  
Sean A. Burnap ◽  
Bhawana Singh ◽  
Hashim Ali ◽  
...  
Keyword(s):  
Intensive Care ◽  
Neutralizing Antibody ◽  
Icu Mortality ◽  
Icu Patients ◽  
Interaction Partners ◽  
Mannose Binding ◽  
Galectin 3 ◽  
The Complement System ◽  
Mortality Hazard Ratio

AbstractPrognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro.

scholarly journals SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

2020 ◽  
Author(s):  
Manuel Mayr ◽  
Clemens Gutmann ◽  
Kaloyan Takov ◽  
Sean Burnap ◽  
Bhawana Singh ◽  
...  
Keyword(s):  
Intensive Care ◽  
Neutralizing Antibody ◽  
Icu Mortality ◽  
Icu Patients ◽  
Mortality Hazard ◽  
Interaction Partners ◽  
Galectin 3 ◽  
The Complement System ◽  
Mortality Hazard Ratio ◽  
Age And Sex

Abstract Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.

scholarly journals Accurate Measurement of Functional Residual Capacity and Oxygen Consumption of Patients on Mechanical Ventilation

1983 ◽  
Vol 11 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Kevin R. Cooper ◽  
Peter A. Boswell
Keyword(s):  
Intensive Care Unit ◽  
Mechanical Ventilation ◽  
Intensive Care ◽  
Oxygen Consumption ◽  
Functional Residual Capacity ◽  
Lung Model ◽  
Capacity Measurement ◽  
Icu Patients ◽  
Residual Capacity

We developed an apparatus and technique for the simultaneous measurement of functional residual capacity and oxygen uptake (V̇O2) for use in intensive care unit (ICU) patients. The accuracy of the functional residual capacity measurement was proven using an in vitro lung model and the reproducibility of this measurement was established by use in ICU patients. We tested the accuracy of the V̇O2 measurement in comparison with two other methods in common use among ICU patients and our method proved accurate. We conclude that this technique for measurement of functional residual capacity and V̇O2 is highly accurate and easily applied to patients on any mode of mechanical ventilation.

scholarly journals Lactate Kinetics Reflect Organ Dysfunction and Are Associated with Adverse Outcomes in Intensive Care Unit Patients with COVID-19 Pneumonia: Preliminary Results from a GREEK Single-Centre Study

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 386
Author(s):  
Alice G. Vassiliou ◽  
Edison Jahaj ◽  
Ioannis Ilias ◽  
Vassiliki Markaki ◽  
Sotirios Malachias ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Blood Lactate ◽  
Organ Dysfunction ◽  
Apache Ii ◽  
Icu Mortality ◽  
Icu Patients ◽  
Time Pattern ◽  
Cox Regression Analysis ◽  
Icu Admission

Coronavirus disease-19 (COVID-19) continues to be a health threat worldwide. Increased blood lactate is common in intensive care unit (ICU) patients; however, its association with outcomes in ICU COVID-19 patients remains currently unexplored. In this retrospective, observational study we assessed whether lactate is associated with outcomes in COVID-19 patients. Blood lactate was measured on ICU admission and thereafter daily up to day 14 in 45 patients with confirmed COVID-19 pneumonia. Acute physiology and chronic health evaluation (APACHE II) was calculated on ICU admission, and sequential organ failure assessment (SOFA) score was assessed on admission and every second day. The cohort was divided into survivors and non-survivors based on 28-day ICU mortality (24.4%). Cox regression analysis revealed that maximum lactate on admission was independently related to 28-day ICU mortality with time in the presence of APACHE II (RR = 2.45, p = 0.008). Lactate’s area under the curve for detecting 28-day ICU mortality was 0.77 (p = 0.008). Mixed model analysis showed that mean daily lactate levels were higher in non-survivors (p < 0.0001); the model applied on SOFA scores showed a similar time pattern. Thus, initial blood lactate was an independent outcome predictor in COVID-19 ICU patients. The time course of lactate mirrors organ dysfunction and is associated with poor clinical outcomes.

scholarly journals Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system

2013 ◽  
Vol 304 (12) ◽  
pp. L863-L872 ◽  
Author(s):  
Daniel Rittirsch ◽  
Michael A. Flierl ◽  
Brian A. Nadeau ◽  
Danielle E. Day ◽  
Markus S. Huber-Lang ◽  
...  
Keyword(s):  
Complement System ◽  
Serine Proteases ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Neutrophil Accumulation ◽  
The Complement System ◽  
Dose Dependent

Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.

scholarly journals Activity of a New Cephalosporin, CXA-101 (FR264205), against β-Lactam-Resistant Pseudomonas aeruginosa Mutants Selected In Vitro and after Antipseudomonal Treatment of Intensive Care Unit Patients

2010 ◽  
Vol 54 (3) ◽  
pp. 1213-1217 ◽  
Author(s):  
Bartolome Moya ◽  
Laura Zamorano ◽  
Carlos Juan ◽  
José L. Pérez ◽  
Yigong Ge ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Pseudomonas Aeruginosa ◽  
Intensive Care ◽  
Efflux Pump ◽  
Multidrug Resistant ◽  
Icu Patients ◽  
Resistant Strains ◽  
High Level ◽  
Level Resistance

ABSTRACT CXA-101, previously designated FR264205, is a new antipseudomonal cephalosporin. We evaluated the activity of CXA-101 against a highly challenging collection of β-lactam-resistant Pseudomonas aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit (ICU) patients. The in vitro mutants investigated included strains with multiple combinations of mutations leading to several degrees of AmpC overexpression (ampD, ampDh2, ampDh3, and dacB [PBP4]) and porin loss (oprD). CXA-101 remained active against even the AmpD-PBP4 double mutant (MIC = 2 μg/ml), which shows extremely high levels of AmpC expression. Indeed, this mutant showed high-level resistance to all tested β-lactams, except carbapenems, including piperacillin-tazobactam (PTZ), aztreonam (ATM), ceftazidime (CAZ), and cefepime (FEP), a cephalosporin considered to be relatively stable against hydrolysis by AmpC. Moreover, CXA-101 was the only β-lactam tested (including the carbapenems imipenem [IMP] and meropenem [MER]) that remained fully active against the OprD-AmpD and OprD-PBP4 double mutants (MIC = 0.5 μg/ml). Additionally, we tested a collection of 50 sequential isolates that were susceptible or resistant to penicillicins, cephalosporins, carbapenems, or fluoroquinolones that emerged during treatment of ICU patients. All of the mutants resistant to CAZ, FEP, PTZ, IMP, MER, or ciprofloxacin showed relatively low CXA-101 MICs (range, 0.12 to 4 μg/ml; mean, 1 to 2 μg/ml). CXA-101 MICs of pan-β-lactam-resistant strains ranged from 1 to 4 μg/ml (mean, 2.5 μg/ml). As described for the in vitro mutants, CXA-101 retained activity against the natural AmpD-PBP4 double mutants, even when these exhibited additional overexpression of the MexAB-OprM efflux pump. Therefore, clinical trials are needed to evaluate the usefulness of CXA-101 for the treatment of P. aeruginosa nosocomial infections, particularly those caused by multidrug-resistant isolates that emerge during antipseudomonal treatments.

scholarly journals ICU-Mortality in Old and Very Old Patients Suffering From Sepsis and Septic Shock

2021 ◽  
Vol 8 ◽  
Author(s):  
Raphael Romano Bruno ◽  
Bernhard Wernly ◽  
Behrooz Mamandipoor ◽  
Richard Rezar ◽  
Stephan Binnebössel ◽  
...  
Keyword(s):  
Septic Shock ◽  
Intensive Care ◽  
Length Of Stay ◽  
Research Database ◽  
Icu Mortality ◽  
Icu Patients ◽  
Old Patients ◽  
Very Old ◽  
Sepsis And Septic Shock ◽  
Very Old Patients

Purpose: Old (&gt;64 years) and very old (&gt;79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care.Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65–79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients (n = 1054) was also conducted.Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p &lt; 0.001), and the rate of a prolonged ICU stay was lower (&gt;168 h; 9 vs. 12%; p &lt; 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09–1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10–2.06; p = 0.01).Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.

scholarly journals Hyperchloremia in critically ill patients: association with outcomes and prediction using electronic health record data

2020 ◽  
Vol 20 (S14) ◽  
Author(s):  
Pete Yeh ◽  
Yiheng Pan ◽  
L. Nelson Sanchez-Pinto ◽  
Yuan Luo
Keyword(s):  
Intensive Care ◽  
Supervised Learning ◽  
Medical Information ◽  
Kidney Injury ◽  
Learning Model ◽  
Multiple Organ ◽  
Icu Mortality ◽  
Electronic Health Record Data ◽  
Icu Patients ◽  
Clinical Records

Abstract Background Increased chloride in the context of intravenous fluid chloride load and serum chloride levels (hyperchloremia) have previously been associated with increased morbidity and mortality in select subpopulations of intensive care unit (ICU) patients (e.g patients with sepsis). Here, we study the general ICU population of the Medical Information Mart for Intensive Care III (MIMIC-III) database to corroborate these associations, and propose a supervised learning model for the prediction of hyperchloremia in ICU patients. Methods We assessed hyperchloremia and chloride load and their associations with several outcomes (ICU mortality, new acute kidney injury [AKI] by day 7, and multiple organ dysfunction syndrome [MODS] on day 7) using regression analysis. Four predictive supervised learning classifiers were trained to predict hyperchloremia using features representative of clinical records from the first 24h of adult ICU stays. Results Hyperchloremia was shown to have an independent association with increased odds of ICU mortality, new AKI by day 7, and MODS on day 7. High chloride load was also associated with increased odds of ICU mortality. Our best performing supervised learning model predicted second-day hyperchloremia with an AUC of 0.76 and a number needed to alert (NNA) of 7—a clinically-actionable rate. Conclusions Our results support the use of predictive models to aid clinicians in monitoring for and preventing hyperchloremia in high-risk patients and offers an opportunity to improve patient outcomes.

Plasma 25-Hydroxyvitamin D Level at Admission Predicts Unfavorable Outcome in Intensive Care Unit Patients

2020 ◽  
Vol 22 (3) ◽  
pp. 388-396
Author(s):  
Dhouha Maamer ◽  
Ahlem Trifi ◽  
Mohamed Kacem Ben Fradj ◽  
Foued Daly ◽  
Mohamed Bassem Hammami ◽  
...  
Keyword(s):  
Adverse Event ◽  
Intensive Care ◽  
Adverse Events ◽  
Major Adverse Event ◽  
Icu Mortality ◽  
Icu Patients ◽  
Hydroxyvitamin D ◽  
Icu Stay ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Introduction: Patients in intensive care units (ICUs) are at high risk of unfavorable outcomes. Considering the role of vitamin D (Vit D) in cardiovascular and immune functions, Vit D deficiency could affect ICU patients’ outcomes. This study aimed to evaluate Vit D status and its predictive value for outcome in ICU patients. Patients and Methods: A total of 169 ICU patients were followed during ICU stay. Primary outcome was the occurrence of at least one major adverse event; secondary outcomes were organ failure, septic shock, ICU-acquired infection, other adverse events, and ICU mortality. Plasma 25-hydroxyvitamin D (25(OH)D) was assessed by immunoassay. Multivariate Cox regression analyses were performed to test the associations of low 25(OH)D levels with poor outcomes. Results: Around 75% of patients had 25(OH)D levels <12 ng/ml. During their ICU stay, 114 patients experienced a major adverse event, 85 patients presented an ICU-acquired infection, and 22 patients died. Plasma 25(OH)D levels <12 ng/ml were associated with higher risk of major adverse events, Hazard ratio [95% CI], 4.47 [1.77, 11.3], p = .020, and ICU-acquired infection, 2.67 [1.01, 7.42], p = .049, but not with increased risk of ICU mortality. Conclusions: Hypovitaminosis D is very common in ICU patients. Results of the present study show that low plasma 25(OH)D levels are associated with increased risk of unfavorable outcomes in these patients. Additional research is needed to investigate the impact of Vit D status and effect of Vit D supplementation in ICU patients.

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