scholarly journals Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis

2020 ◽  
Vol 48 (3) ◽  
pp. 221-228
Author(s):  
Daniëlle MH Beurskens ◽  
Martine E Bol ◽  
Tammo Delhaas ◽  
Marcel CG van de Poll ◽  
Chris PM Reutelingsperger ◽  
...  
Keyword(s):  
Organ Failure ◽  
Early Stage ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Pathophysiological Mechanism ◽  
Heparin Binding ◽  
Sidestream Dark Field ◽  
Glycocalyx Thickness

Microcirculatory alterations play an important role in the early phase of sepsis. Shedding of the endothelial glycocalyx is regarded as a central pathophysiological mechanism causing microvascular dysfunction, contributing to multiple organ failure and death in sepsis. The objective of this study was to investigate whether endothelial glycocalyx thickness at an early stage in septic patients relates to clinical outcome. We measured the perfused boundary region (PBR), which is inversely proportional to glycocalyx thickness, of sublingual microvessels (5–25 µm) using sidestream dark field imaging. The PBR in 21 patients with sepsis was measured within 24 h of admission to the intensive care unit (ICU). In addition, we determined plasma markers of microcirculatory dysfunction and studied their correlation with PBR and mortality. Endothelial glycocalyx thickness in sepsis was significantly lower for non-survivors as compared with survivors, indicated by a higher PBR of 1.97 [1.85, 2.19]µm compared with 1.76 [1.59, 1.97] µm, P=0.03. Admission PBR was associated with hospital mortality with an area under the curve of 0.778 based on the receiver operating characteristic curve. Furthermore, PBR correlated positively with angiopoietin-2 (rho=0.532, P=0.03), indicative of impaired barrier function. PBR did not correlate with Acute Physiology and Chronic Health Evaluation IV (APACHE IV), Sequential Organ Failure Assessment score (SOFA score), lactate, syndecan-1, angiopoietin-1 or heparin-binding protein. An increased PBR within the first 24 h after ICU admission is associated with mortality in sepsis. Further research should be aimed at the pathophysiological importance of glycocalyx shedding in the development of multi-organ failure and at therapies attempting to preserve glycocalyx integrity.

scholarly journals Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs

2019 ◽  
Vol 316 (6) ◽  
pp. H1538-H1551 ◽  
Author(s):  
Boris Schmitz ◽  
Hannah Niehues ◽  
Malte Lenders ◽  
Lothar Thorwesten ◽  
Andreas Klose ◽  
...  
Keyword(s):  
High Intensity ◽  
Interval Training ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
High Intensity Interval Training ◽  
Sidestream Dark Field ◽  
Sidestream Dark Field Imaging ◽  
High Intensity Interval ◽  
Glycocalyx Thickness

High-intensity interval training (HIIT) has been proposed to exert vasculoprotective effects. This study aimed to evaluate whether HIIT affects the microvasculature, including the endothelial glycocalyx barrier, and to identify associated microRNAs (miRNAs). Fifty healthy participants (23.1 ± 3.0 yr) performed a 4-wk 4 × 30-s all-out running HIIT. Sidestream dark-field imaging was performed at baseline and follow-up to detect changes of the sublingual microvasculature including the endothelial glycocalyx. Exercise parameters were determined by continuous running field test and documentation of high-intensity runs. miRNAs potentially associated with glycocalyx thickness were selected by structured literature search and blood samples for miRNA, and lactate measurements were drawn at baseline and follow-up HIIT. At baseline, a correlation between maximal exercise performance capacity and glycocalyx thickness (determined by perfused boundary region) was detected ( P = 0.045, r = 0.303). Increased exercise performance at follow-up also correlated with glycocalyx thickness ( P = 0.031, r = 0.416), and increased high-intensity sprinting speed was associated with an increased number of perfused vessels ( P = 0.0129, r = 0.449). Literature search identified miR-143, -96-5p, and -24, which were upregulated by HIIT already at baseline and showed an association with peak blood lactate levels after sprints (all P < 0.05). Moreover, increased baseline miR-143 levels predicted increased glycocalyx thickness at follow-up (AUCmiR-143 = 0.92, 95% confidence interval, 0.81–1.0, P = 0.0008). Elevated resting miR-126 levels after the intervention were associated with cell-free versican mRNA levels. We conclude that HIIT induces changes in the endothelial glycocalyx of the microvasculature. Associated miRNAs such as miR-143 may represent a tool for monitoring early vasculoprotective adaptations to physical activity. NEW & NOTEWORTHY High-intensity interval training is known to improve health-related fitness in general and in lifestyle-induced chronic diseases. To visualize microvasculature structure and to detect exercise-induced changes, sublingual sidestream dark-field imaging microscopy was used, and circulating miRNAs were measured. This study shows that exercise-induced changes correlate with associated circulating miRNA, which might be useful for monitoring vasculoprotective effects. Furthermore, sidestream dark-field imaging may represent a sensitive tool for the early detection of exercise-induced systemic vascular changes.

Abstract MP61: Evidence of Impaired Microvascular Function a Decade After Delivery in Women With Placental Malperfusion Lesions

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Alisse Hauspurg ◽  
Judith Brands ◽  
Robin Gandley ◽  
Matthew F Muldoon ◽  
William Tony Parks ◽  
...  
Keyword(s):  
Disease Risk ◽  
Gestational Hypertension ◽  
Boundary Region ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation ◽  
Dark Field Imaging ◽  
Median Diameter ◽  
History Of

Introduction: Maternal vascular malperfusion (MVM) lesions in the placenta are characterized by incomplete vascular remodeling and vessel features similar to atherosclerosis. MVM lesions indicate a maladaptive maternal vascular response to pregnancy, are often detected in hypertensive disorders of pregnancy (HDP), and may provide a pathologic link to future cardiovascular disease. The endothelial glycocalyx is a glycoprotein-rich layer that is critical for microvascular health and damage may have an important role in the pathophysiology of microcardiovascular disease risk. Hypothesis: We hypothesized that women with malperfusion lesions of the placenta are more likely to evidence microvascular glycocalyx derangement a decade after delivery compared to women without these lesions and that this effect would be most pronounced among women with a history of HDP. Methods: A total of 412 women with placental pathology (N=129 with MVM lesions, N=283 without MVM lesions) were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a blinded perinatal pathologist . HDP (including preeclampsia and gestational hypertension) were abstracted from the medical record. Glycocalyx barrier function was assessed using sublingual sidestream dark field imaging, with reduction defined as deeper penetration of red blood cells (RBCs) into the glycocalyx of the sublingual microcirculation (5-25μm diameter). We compared the median diameter (size) of microvessels, penetration of RBCs into the glycocalyx (perfused boundary region, PBR) and microvascular density (total length of perfused microvessels/mm 2 surface area) in women with and without MVM lesions. Results: Women with placental MVM lesions had smaller-sized sublingual vessels (median 8.59 μM [IQR 8.12, 9.19] vs. 9.01 μM [IQR 8.37, 9.64]; p<0.001), and a lower density of vessels compared to women without lesions. Glycocalyx perfused boundary region was unexpectedly lower in women with MVM lesions (median 2.20 μM [IQR 2.06, 2.43] vs. 2.32 μM [IQR 2.15, 2.50]; p=0.003) in 10-19 μM vessels. Women with HDP and MVM lesions appear to be the most impacted, with the smallest size vessels (median 8.47 [IQR 8.09-9.13]) and the lowest glycocalyx PBR across all vessel sizes. Women with MVM lesions without a HDP similarly had evidence of microvascular glycocalyx derangement whereas women with HDP without placental lesions had a glycocalyx profile similar to women without MVM or a history of HDP. Conclusions: A decade after delivery, women with a history of placental malperfusion lesions had alterations in microvascular perfusion. Women with MVM lesions and a history of HDP appear to be the most severely impacted, which may reflect an underlying maladaptive vascular phenotype detected in the placenta at the time of pregnancy that might provide pathologic insight into future maternal microvascular health.

New insights into antiphospholipid-related endothelial dysfunction by assessment of vascular glycocalyx layer: results from a preliminary cross-sectional study

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 157-164 ◽  
Author(s):  
S Miranda ◽  
P Billoir ◽  
M Le Besnerais ◽  
R Joannides ◽  
V Richard ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Plasma Level ◽  
Thiobarbituric Acid ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Cross Sectional ◽  
Early Atherosclerosis

Introduction Antiphospholipid syndrome (APS) is associated with greater atherothrombotic risk and endothelial dysfunction, suggesting that endothelial glycocalyx is impaired in this disease. Objectives The aim was to investigate the endothelial glycocalyx and the relationship between glycocalyx markers, endothelial dysfunction parameters and atherosclerotic markers in APS. Methods A total of 15 primary arterial APS patients and healthy controls were included in the study. Glycocalyx was assessed in both groups by sublingual sidestream dark field imaging and syndecan-1 plasma level. Endothelial function was evaluated by brachial artery flow-mediated dilatation (FMD) and early atherosclerosis by carotid intima media thickness (IMT). Thrombotic profile was also performed by measuring the plasma level of the tissue factor (TF). Results APS patients had significantly increased syndecan-1 plasma level 38.6 ± 5.0 pg/ml vs. 19.1 ± 3.5 pg/ml; p < 0.01 and a reduced glycocalyx thickness 0.26 ± 0.03 µm vs. 0.75 ± 0.07 µm; p < 0.01 compared with control. FMD was impaired in APS patients compared with control, 5.68% ± 0.42 vs. 8.29 ± 0.30, p < 0.01, respectively. IMT was significantly increased in APS patients compared with control, 0.52 ± 0.13 mm vs. 0.40 ± 0.06 mm, p < 0.01, respectively. Soluble TF, thiobarbituric acid-reactive substances levels were increased in the sera from APS patients compared with control. Conclusions This preliminary study supports, for the first time, that in APS patients endothelial glycocalyx is impaired, which could lead to thrombosis, endothelial dysfunction and early atherosclerosis.

scholarly journals From Macrohemodynamic to the Microcirculation

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Abele Donati ◽  
Roberta Domizi ◽  
Elisa Damiani ◽  
Erica Adrario ◽  
Paolo Pelaia ◽  
...  
Keyword(s):  
Organ Failure ◽  
Imaging Technique ◽  
Round Table ◽  
Dark Field ◽  
Leukocyte Rolling ◽  
Capillary Leakage ◽  
Therapeutic Approaches ◽  
Sidestream Dark Field ◽  
Heterogeneous Distribution ◽  
Information Focus

ICU patients need a prompt normalization of macrohemodynamic parameters. Unfortunately, this optimization sometimes does not protect patients from organ failure development. Prevention or treatment of organ failure needs another target to be pursued: the microcirculatory restoration. Microcirculation is the ensemble of vessels of maximum 100 m in diameter. Nowadays the Sidestream Dark Field (SDF) imaging technique allows its bedside investigation and a recent round-table conference established the criteria for its evaluation. First, microcirculatory derangements have been studied in sepsis: they are mainly characterized by a reduction of vessel density, an alteration of flow, and a heterogeneous distribution of perfusion. Endothelial malfunction and glycocalyx rupture were proved to be the main reasons for the observed microthrombi, capillary leakage, leukocyte rolling, and rouleaux phenomenon, even if further studies are necessary for a better explanation. Therapeutic approaches targeting microcirculation are under investigation. Microcirculatory alterations have been recently demonstrated in other diseases such as hypovolemia and cardiac failure but this issue still needs to be explored. The aim of this paper is to gather the already known information, focus the reader’s attention on the importance of microvascular physiopathology in critical illness, and prompt him to actively participate to achieve a more comprehensive understanding of the issue.

scholarly journals A Nomogram-Based Model to Predict Neoplastic Risk For Patients With Gallbladder Polyps

2021 ◽  
Author(s):  
Xudong Zhang ◽  
Jin-Cheng Wang ◽  
Baoqiang Wu ◽  
Tao Li ◽  
Lei Jin ◽  
...  
Keyword(s):  
Clinical Decision Making ◽  
Early Stage ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Training Group ◽  
Clinical Decision ◽  
Polyp Size ◽  
Training Cohort ◽  
Discrimination Ability ◽  
Gallbladder Polyps

Abstract Background: Gallbladder polyps (GBPs) assessment seeks to identify early-stage gallbladder carcinoma (GBC). Many studies have analyzed the risk factors for malignant GBPs, and we try to establish a more accurate predictive model for potential neoplastic polyps in patients with GBPs.Methods: This retrospective study developed a nomogram-based model in a training cohort of 233 GBP patients. Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. Spearman correlation and logistic regression analysis were used to identify independent predictors and establish a nomogram model. An internal validation was conducted in 225 consecutive patients. Performance of models was evaluated through the receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Results: Age, cholelithiasis, CEA, polyp size and sessile were confirmed as independent predictors for neoplastic potential of GBPs in the training group. Compared with other proposed prediction methods, the established nomogram model presented good discrimination ability in the training cohort (area under the curve [AUC]: 0.845) and the validation cohort (AUC: 0.836). DCA demonstrated the most clinical benefits can be provided by the nomogram. Conclusions: Our developed preoperative nomogram model can successfully evaluate the neoplastic potential of GBPs based on simple clinical variables, that maybe useful for clinical decision-making.

scholarly journals C-Reactive Protein Level May Predict the Risk of COVID-19 Aggravation

2020 ◽  
Vol 7 (5) ◽  
Author(s):  
Guyi Wang ◽  
Chenfang Wu ◽  
Quan Zhang ◽  
Fang Wu ◽  
Bo Yu ◽  
...  
Keyword(s):  
Early Stage ◽  
Characteristic Curve ◽  
Laboratory Data ◽  
Area Under The Curve ◽  
Threshold Value ◽  
Clinical Findings ◽  
Optimal Threshold ◽  
C Reactive Protein ◽  
Related Factors ◽  
Reactive Protein

Abstract Background Clinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study aimed to describe the clinical characteristics of these patients, analyze related factors, and explore predictive markers of the disease aggravation. Methods Clinical and laboratory data of nonsevere adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. The receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP). Results About 7.7% (16/209) of nonsevere adult COVID-19 patients progressed to severe cases after admission. Compared with nonsevere patients, the aggravated patients had much higher levels of CRP (median [range], 43.8 [12.3–101.9] mg/L vs 12.1 [0.1–91.4] mg/L; P = .000). A regression analysis showed that CRP was significantly associated with aggravation of nonsevere COVID-19 patients, with an area under the curve of 0.844 (95% confidence interval, 0.761–0.926) and an optimal threshold value of 26.9 mg/L. Conclusions CRP could be a valuable marker to anticipate the possibility of aggravation of nonsevere adult COVID-19 patients, with an optimal threshold value of 26.9 mg/L.

scholarly journals An App for Detecting Bullying of Nurses Using Convolutional Neural Networks and Web-Based Computerized Adaptive Testing: Development and Usability Study (Preprint)

2019 ◽  
Author(s):  
Shu-Ching Ma ◽  
Willy Chou ◽  
Tsair-Wei Chien ◽  
Julie Chi Chow ◽  
Yu-Tsen Yeh ◽  
...  
Keyword(s):  
Neural Networks ◽  
Convolutional Neural Networks ◽  
Workplace Bullying ◽  
Computerized Adaptive Testing ◽  
Early Stage ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Adaptive Testing ◽  
Web Based ◽  
Nurse Bullying

BACKGROUND Workplace bullying has been measured in many studies to investigate its effects on mental health issues. However, none have used web-based computerized adaptive testing (CAT) with bully classifications and convolutional neural networks (CNN) for reporting the extent of individual bullying in the workplace. OBJECTIVE This study aims to build a model using CNN to develop an app for automatic detection and classification of nurse bullying-levels, incorporated with online Rasch computerized adaptive testing, to help assess nurse bullying at an earlier stage. METHODS We recruited 960 nurses working in a Taiwan Ch-Mei hospital group to fill out the 22-item Negative Acts Questionnaire-Revised (NAQ-R) in August 2012. The k-mean and the CNN were used as unsupervised and supervised learnings, respectively, for: (1) dividing nurses into three classes (n=918, 29, and 13 with suspicious mild, moderate, and severe extent of being bullied, respectively); and (2) building a bully prediction model to estimate 69 different parameters. Finally, data were separated into training and testing sets in a proportion of 70:30, where the former was used to predict the latter. We calculated the sensitivity, specificity, and receiver operating characteristic curve (area under the curve [AUC]), along with the accuracy across studies for comparison. An app predicting the respondent bullying-level was developed, involving the model’s 69 estimated parameters and the online Rasch CAT module as a website assessment. RESULTS We observed that: (1) the 22-item model yields higher accuracy rates for three categories, with an accuracy of 94% for the total 960 cases, and accuracies of 99% (AUC 0.99; 95% CI 0.99-1.00) and 83% (AUC 0.94; 95% CI 0.82-0.99) for the lower and upper groups (cutoff points at 49 and 66 points) based on the 947 cases and 42 cases, respectively; and (2) the 700-case training set, with 95% accuracy, predicts the 260-case testing set reaching an accuracy of 97. Thus, a NAQ-R app for nurses that predicts bullying-level was successfully developed and demonstrated in this study. CONCLUSIONS The 22-item CNN model, combined with the Rasch online CAT, is recommended for improving the accuracy of the nurse NAQ-R assessment. An app developed for helping nurses self-assess workplace bullying at an early stage is required for application in the future.

scholarly journals An App Developed for Detecting Nurse Burnouts Using the Convolutional Neural Networks in Microsoft Excel: Population-Based Questionnaire Study (Preprint)

2019 ◽  
Author(s):  
Yi-Lien Lee ◽  
Willy Chou ◽  
Tsair-Wei Chien ◽  
Po-Hsin Chou ◽  
Yu-Tsen Yeh ◽  
...  
Keyword(s):  
Predictive Accuracy ◽  
Early Stage ◽  
Medical Center ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Maslach Burnout Inventory ◽  
Well Being ◽  
Population Based ◽  
Psychological Status ◽  
Sensitivity Specificity

BACKGROUND Burnout (BO), a critical syndrome particularly for nurses in health care settings, substantially affects their physical and psychological status, the institute’s well-being, and indirectly, patient outcomes. However, objectively classifying BO levels has not been defined and noticed in the literature. OBJECTIVE The aim of this study is to build a model using the convolutional neural network (CNN) to develop an app for automatic detection and classification of nurse BO using the Maslach Burnout Inventory–Human Services Survey (MBI-HSS) to help assess nurse BO at an earlier stage. METHODS We recruited 1002 nurses working in a medical center in Taiwan to complete the Chinese version of the 20-item MBI-HSS in August 2016. The k-mean and CNN were used as unsupervised and supervised learnings for dividing nurses into two classes (n=531 and n=471 of suspicious BO+ and BO−, respectively) and building a BO predictive model to estimate 38 parameters. Data were separated into training and testing sets in a proportion 70%:30%, and the former was used to predict the latter. We calculated the sensitivity, specificity, and receiver operating characteristic curve (area under the curve) across studies for comparison. An app predicting respondent BO was developed involving the model’s 38 estimated parameters for a website assessment. RESULTS We observed that (1) the 20-item model yields a higher accuracy rate (0.95) with an area under the curve of 0.97 (95% CI 0.94-0.95) based on the 1002 cases, (2) the scheme named matching personal response to adapt for the correct classification in model drives the prior model’s predictive accuracy at 100%, (3) the 700-case training set with 0.96 accuracy predicts the 302-case testing set reaching an accuracy of 0.91, and (4) an available MBI-HSS app for nurses predicting BO was successfully developed and demonstrated in this study. CONCLUSIONS The 20-item model with the 38 parameters estimated by using CNN for improving the accuracy of nurse BO has been particularly demonstrated in Excel (Microsoft Corp). An app developed for helping nurses to self-assess job BO at an early stage is required for application in the future.

scholarly journals Links between Endothelial Glycocalyx Changes and Microcirculatory Parameters in Septic Patients

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 790
Author(s):  
Egle Belousoviene ◽  
Inga Kiudulaite ◽  
Vidas Pilvinis ◽  
Andrius Pranskunas
Keyword(s):  
Blood Vessels ◽  
Prospective Observational Study ◽  
Microvascular Dysfunction ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Sidestream Dark Field ◽  
Sublingual Microcirculation ◽  
Endothelial Surface ◽  
Significant Damage ◽  
Video Microscope

The glycocalyx is an endothelial surface layer that is essential for maintaining microvascular homeostasis. Impaired integrity of the endothelial glycocalyx may be directly related to the development of microvascular dysfunction. To explore this hypothesis, we conducted a prospective observational study on adult patients diagnosed with sepsis. The study aimed to evaluate the degree of damage to the glycocalyx and to identify correlations between microcirculatory parameters and glycocalyx thickness based on capillary diameter. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field video microscope. A sidestream dark field video microscope attached to a GlycoCheck monitor was used to determine the perfused boundary regions (PBRs) of sublingual blood vessels grouped by diameter (5–9 μm, 10–19 μm, and 20–25 μm). We identified significant damage to the glycocalyx in sublingual blood vessels of all the aforementioned diameters in septic patients compared to healthy age-matched controls. Furthermore, we found that the PBRs of the smallest capillaries (diameter class 5–9µm) correlated moderately and inversely with both total and perfused blood vessel densities. Collectively, our data suggest that there may be a functional relationship between damage to the endothelial glycocalyx of the smallest capillaries and alterations in the microcirculation observed in response to sepsis.

scholarly journals Microvascular dysfunction in COVID-19: the MYSTIC study

Angiogenesis ◽  
2020 ◽  
Author(s):  
Alexandros Rovas ◽  
Irina Osiaevi ◽  
Konrad Buscher ◽  
Jan Sackarnd ◽  
Phil-Robin Tepasse ◽  
...  
Keyword(s):  
Microvascular Dysfunction ◽  
Boundary Region ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Vascular Involvement ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Levels ◽  
Vascular Density ◽  
Sidestream Dark Field ◽  
Cross Sectional

Abstract Rationale Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. Objectives To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. Methods Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. Measurements and main results COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4–6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. Conclusions Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.

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