scholarly journals Endothelial, Immunothrombotic, and Inflammatory Biomarkers in the Risk of Mortality in Critically Ill COVID-19 Patients: The Role of Dexamethasone

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1249
Author(s):  
Chrysi Keskinidou ◽  
Alice G. Vassiliou ◽  
Alexandros Zacharis ◽  
Edison Jahaj ◽  
Parisis Gallos ◽  
...  

Endothelial dysfunction, coagulation and inflammation biomarkers are increasingly emerging as prognostic markers of poor outcomes and mortality in severe and critical COVID-19. However, the effect of dexamethasone has not been investigated on these biomarkers. Hence, we studied potential prognostic biomarkers of mortality in critically ill COVID-19 patients who had either received or not dexamethasone. Biomarker serum levels were measured on intensive care unit (ICU) admission (within 24 h) in 37 dexamethasone-free and 29 COVID-19 patients who had received the first dose (6 mg) of dexamethasone. Receiver operating characteristic (ROC) curves were generated to assess their value in ICU mortality prediction, while Kaplan–Meier analysis was used to explore associations between biomarkers and survival. In the dexamethasone-free COVID-19 ICU patients, non-survivors had considerably higher levels of various endothelial, immunothrombotic and inflammatory biomarkers. In the cohort who had received one dexamethasone dose, non-survivors had higher ICU admission levels of only soluble (s) vascular cell adhesion molecule-1 (VCAM-1), soluble urokinase-type plasminogen activator receptor (suPAR) and presepsin. As determined from the generated ROC curves, sVCAM-1, suPAR and presepsin could still be reliable prognostic ICU mortality biomarkers, following dexamethasone administration (0.7 < AUC < 0.9). Moreover, the Kaplan–Meier survival analysis showed that patients with higher than the median values for sVCAM-1 or suPAR exhibited a greater mortality risk than patients with lower values (Log-Rank test, p < 0.01). In our single-center study, sVCAM-1, suPAR and presepsin appear to be valuable prognostic biomarkers in assessing ICU mortality risk in COVID-19 patients, even following dexamethasone administration.

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3773
Author(s):  
Alice G. Vassiliou ◽  
Edison Jahaj ◽  
Maria Pratikaki ◽  
Stylianos E. Orfanos ◽  
Ioanna Dimopoulou ◽  
...  

We aimed to examine whether low intensive care unit (ICU) admission 25-hydroxyvitamin D (25(OH)D) levels are associated with worse outcomes of COVID-19 pneumonia. This was a prospective observational study of SARS-CoV2 positive critically ill patients treated in a multidisciplinary ICU. Thirty (30) Greek patients were included, in whom 25(OH)D was measured on ICU admission. Eighty (80%) percent of patients had vitamin D deficiency, and the remaining insufficiency. Based on 25(OH)D levels, patients were stratified in two groups: higher and lower than the median value of the cohort (15.2 ng/mL). The two groups did not differ in their demographic or clinical characteristics. All patients who died within 28 days belonged to the low vitamin D group. Survival analysis showed that the low vitamin D group had a higher 28-day survival absence probability (log-rank test, p = 0.01). Critically ill COVID-19 patients who died in the ICU within 28 days appeared to have lower ICU admission 25(OH)D levels compared to survivors. When the cohort was divided at the median 25(OH)D value, the low vitamin D group had an increased risk of 28-day mortality. It seems plausible, therefore, that low 25(OH)D levels may predispose COVID-19 patients to an increased 28-day mortality risk.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 186
Author(s):  
Alice G. Vassiliou ◽  
Chrysi Keskinidou ◽  
Edison Jahaj ◽  
Parisis Gallos ◽  
Ioanna Dimopoulou ◽  
...  

Endotheliopathy is suggested to be an important feature of COVID-19 in hospitalized patients. To determine whether endotheliopathy is involved in COVID-19-associated mortality, markers of endothelial damage were assessed in critically ill COVID-19 patients upon intensive care unit (ICU) admission. Thirty-eight critically ill COVID-19 patients were included in this observational study, 10 of whom died in the ICU. Endothelial biomarkers, including soluble (s)E-selectin, sP-selectin, angiopoietin 1 and 2 (Ang-1 and Ang-2, respectively), soluble intercellular adhesion molecule 1 (sICAM-1), vascular endothelial growth factor (VEGF), soluble vascular endothelial (VE)-cadherin, and von Willebrand factor (vWf), were measured upon ICU admission. The ICU cohort was subsequently divided into survivors and non-survivors; Kaplan–Meier analysis was used to explore associations between biomarkers and survival, while receiver operating characteristic (ROC) curves were generated to determine their potential prognostic value. sE-selectin, sP-selectin, Ang-2, and sICAM-1 were significantly elevated in ICU non-survivors compared to survivors, and also associated with a higher mortality probability in the Kaplan–Meier analysis. The prognostic values of sE-selectin, Ang-2, and sICAM-1 from the generated ROC curves were greater than 0.85. Hence, we conclude that in our cohort, ICU non-survivors had higher levels of specific endothelial markers compared to survivors. Elevated levels of these markers upon ICU admission could possibly predict mortality in COVID-19.


2021 ◽  
Vol 10 (12) ◽  
pp. 2576
Author(s):  
Izabela Duda ◽  
Łukasz Krzych

Elevated neutrophil gelatinase-associated lipocalin (NGAL) occurs in a wide range of systemic diseases. This study examined the clinical utility of plasma NGAL to predict intensive care unit (ICU) and in-hospital mortality in critically ill patients. A total of 62 patients hospitalized in a mixed ICU were included; pNGAL, creatinine, and C-reactive protein (CRP) were assayed on four consecutive days (D1-D4) following ICU admission. APACHE II score (Acute Physiology and Chronic Health Evaluation) was calculated 24 h post-admission. ICU mortality reached 35% and in-hospital mortality was 39%. The median pNGAL at admission was 142.5 (65.6–298.3) ng/mL. pNGAL was significantly higher in non-survivors compared to survivors. The highest accuracy for ICU mortality prediction was achieved at the pNGAL cutoff of 93.91 ng/mL on D4 area under the curve (AUC) = 0.89; 95%CI 0.69–0.98 and for in-hospital mortality prediction was achieved at the pNGAL cutoff of 176.64 ng/mL on D3 (AUC = 0.86; 95%CI 0.69–0.96). The APACHE II score on ICU admission predicted ICU mortality with AUC = 0.89 (95%CI 0.79–0.96) and in-hospital mortality with AUC = 0.86 (95%CI 0.75–0.94). Although pNGAL on D1 poorly correlated with APACHE II (R = 0.3; p = 0.01), the combination of APACHE II and pNGAL on D1 predicted ICU mortality with AUC = 0.90 (95%CI 0.79–0.96) and in-hospital mortality with AUC = 0.95 (95%CI 0.78–0.99). Maximal CRP during study observation failed to predict ICU mortality (AUC = 0.62; 95%CI 0.49–0.74), but helped to predict in-hospital mortality (AUC = 0.67; 95%CI 0.54–0.79). Plasma NGAL with combination with the indices of critical illness is a useful biomarker for predicting mortality in heterogeneous population of ICU patients.


2021 ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Alaa Alhubaishi ◽  
Ohoud Al Juhani ◽  
Khalid Eljaaly ◽  
Omar Al Harbi ◽  
...  

Abstract Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.


2020 ◽  
Author(s):  
Alcade Rudakemwa ◽  
Amy Lucille Cassidy ◽  
Theogene Twagirumugabe

Abstract Background Reasons for admission at the intensive care units (ICU) for obstetric patients vary from a setting to another. Outcomes from ICU and its prediction models are not well explored in Rwanda because of lack of appropriate scores. This study intended to assess profile and accuracy of predictive models for obstetric patients admitted in ICU in the two public tertiary hospitals in Rwanda.Methods We prospectively collected data from all obstetric patients admitted in the ICU of public referral hospitals in Rwanda from March 2017 to February 2018 to identify reasons for admissions and factors for prognosis. We analysed the accuracy of mortality prediction models including the quick Sequential Organ Failure Assessment (qSOFA) and Modified Early Obstetric Warning Score (MEOWS) by using the Logistic Regression and adjusted Receiver Operating characteristic (ROC) curves. Results Obstetric patients represented 12.8% of all ICU admissions and 1.8% of all deliveries. Sepsis (31.9%) and haemorrhage (25.5%) were the two commonest reasons for ICU admission in our study participants. The overall ICU mortality for our obstetric patients was 54.3% while the average length of stay was 6.6 days. MEOWS score was an independent predictor to mortality (adjusted OR=1.25[1.07-1.46]; p=0.005) and so was the qSOFA score (adjusted OR=2.81[1.25-6.30]; p=0.012). The adjusted Area Under the ROC (AUROC) for MEOWS was 0.773[0.666-0.880] and that of the qSOFA was 0.764[0.654-0.873] signing fair accuracies for ICU mortality prediction in these settings for both models.Conclusion Sepsis is the commonest reason for admissions to ICU for obstetric patients in Rwanda. Simple models comprising MEOWS and qSOFA could accurately predict the mortality for those patients but further larger studies are needed before generalization.


2020 ◽  
pp. 109980042094448
Author(s):  
Alice G. Vassiliou ◽  
Zafeiria Mastora ◽  
Edison Jahaj ◽  
Chrysi Keskinidou ◽  
Maria E. Pratikaki ◽  
...  

Background: The increased oxidative stress resulting from the inflammatory responses in sepsis initiates changes in mitochondrial function which may result in organ damage, the most common cause of death in the intensive care unit (ICU). Deficiency of coenzyme Q10 (CoQ10), a key cofactor in the mitochondrial respiratory chain, could potentially disturb mitochondrial bioenergetics and oxidative stress, and may serve as a biomarker of mitochondrial dysfunction. Hence, we aimed to investigate in initially non-septic patients whether CoQ10 levels are decreased in sepsis and septic shock compared to ICU admission, and to evaluate its associations with severity scores, inflammatory biomarkers, and ICU outcomes. Methods: Observational retrospective analysis on 86 mechanically-ventilated, initially non-septic, ICU patients. CoQ10 was sequentially measured on ICU admission, sepsis, septic shock or at ICU discharge. CoQ10 was additionally measured in 25 healthy controls. Inflammatory biomarkers were determined at baseline and sepsis. Results: On admission, ICU patients who developed sepsis had lower CoQ10 levels compared to healthy controls (0.89 vs. 1.04 µg/ml, p < 0.05), while at sepsis and septic shock CoQ10 levels decreased further (0.63 µg/ml; p < 0.001 and 0.42 µg/ml; p < 0.0001, respectively, from admission). In ICU patients who did not develop sepsis, admission CoQ10 levels were also lower than healthy subjects (0.81 µg/ml; p < 0.001) and were maintained at the same levels until discharge. Conclusion: CoQ10 levels in critically-ill patients are low on ICU admission compared to healthy controls and exhibit a further decrease in sepsis and septic shock. These results suggest that sepsis severity leads to CoQ10 depletion.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Zeyu Zhang ◽  
Yufan Zhou ◽  
Kuan Hu ◽  
Yun Huang

Abstract Introduction Intrahepatic cholangiocarcinoma (ICC) stands as the second most common malignant tumor in the liver with poor patient prognosis. Increasing evidences have shown that inflammation plays a significant role in tumor progression, angiogenesis, and metastasis. However, the prognosis significance of inflammatory biomarkers on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is poorly recognized. Methods ICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII), were investigated. Results Receiver operating characteristic (ROC) curves showed no significance in NLR, PLR, and LMR in RFS and OS, while significant results were shown on SII in both RFS (P = 0.035) and OS (P = 0.034) with areas under ROC curve as 0.63 (95%CI 0.52–0.74) and 0.62 (95%CI 0.51–0.72), respectively. Kaplan-Meier curves revealed a statistically significant better survival data in SII-low groups on both RFS (P < 0.001) and OS (P < 0.001). The univariate and multivariate analyses revealed that higher level of SII was independently associated with both poorer RFS time and OS time. However, no significant result was shown on NLR, PLR, or LMR. Conclusion SII is an effective prognostic factor for predicting the prognosis of ICC patient undergone curative hepatectomy, while NLR, PLR, and LMR are not associated with clinical outcomes of these patients.


Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1523
Author(s):  
Huimin Li ◽  
Longxiang Xie ◽  
Qiang Wang ◽  
Yifang Dang ◽  
Xiaoxiao Sun ◽  
...  

Myxofibrosarcoma is a complex genetic disease with poor prognosis. However, more effective biomarkers that forebode poor prognosis in Myxofibrosarcoma remain to be determined. Herein, utilizing gene expression profiling data and clinical follow-up data of Myxofibrosarcoma cases in three independent cohorts with a total of 128 Myxofibrosarcoma samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we constructed an easy-to-use web tool, named Online consensus Survival analysis for Myxofibrosarcoma (OSmfs) to analyze the prognostic value of certain genes. Through retrieving the database, users generate a Kaplan–Meier plot with log-rank test and hazard ratio (HR) to assess prognostic-related genes or discover novel Myxofibrosarcoma prognostic biomarkers. The effectiveness and availability of OSmfs were validated using genes in ever reports predicting the prognosis of Myxofibrosarcoma patients. Furthermore, utilizing the cox analysis data and transcriptome data establishing OSmfs, seven genes were selected and considered as more potentially prognostic biomarkers through overlapping and ROC analysis. In conclusion, OSmfs is a promising web tool to evaluate the prognostic potency and reliability of genes in Myxofibrosarcoma, which may significantly contribute to the enrichment of novelly potential prognostic biomarkers and therapeutic targets for Myxofibrosarcoma.


2021 ◽  
Vol 16 (2) ◽  
pp. 207-215
Author(s):  
Cheah Saw Kian ◽  

Optimal nutritional therapy is important to improve outcome in critically ill population in an intensive care unit (ICU). Although indirect calorimetry (IC) is currently a gold standard for resting energy expenditure (REE) measurement, yet it is still not routinely used in the ICU. A total of 146 mechanically ventilated patients were randomised to receive enteral nutrition (EN) with energy targeted based on continuous indirect calorimetry (IC) measurements (IC group, n=73) or according to 25 kcal/kg/day (SWB group, n=73). Patient characteristics were equally distributed and the IC group showed lower mean measured REE (1668.1 + 231.7 vs 1512.0 + 177.1 kcal, p<0.001). Results also showed a significant deficiency in the daily (-148.8 + 105.1 vs. -4.99 + 44.0 kcal, p<0.001) and total cumulative energy balances (-1165.3 + 958.1 vs. 46.5 + 369.5 kcal, p<0.001) in the SWB group as compared to the IC group. From the Kaplan-Meier survival analysis, we found that ICU mortality was significantly lower in the IC group with better survival probability compared to the SWB group (log-rank test, p = 0.03). However, both groups showed comparable results in terms of ICU length of stay, duration of mechanical ventilation and incidence of feeding intolerance. In conclusion, this study showed that tightly supervised nutritional therapy based on continuous IC measurement provides significantly less mean daily and cumulative energy deficits as well as significantly reduced ICU mortality rate.


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