Admission HbA1c value as a prognostic marker in patients admitted with COVID-19

Background:Diabetes mellitus has been firmly established as a risk factor for the prognosis of COVID-19. However, the impact of pre-COVID-19 glycemic control on prognosis is yet to be fully understood. Our study aimedto establish the effect of HbA1c at admission on the outcome of patients admitted with COVID-19.Methods:It was a prospective observational study of admitted adult patients with confirmed SARS-CoV-2 infection in a tertiary care centre based on data collected from the medical record section using the patient data registry between April 2021 to June 2021. Information regarding demographic and clinical features, laboratory values, and hospital outcomes was collected and analysed.Results:182 patients admitted to the hospital with COVID-19 during the study period were included, their mean age was 48.75 years, the mean HbA1c was 6.1. Males accounted for 69.8% (127) of the sample population. 41.2% (75) were known diabetics. 44.8% (81) were known hypertensives. The mortality rate overall was 25.3% (46). 63.7% (116) had HbA1c values >6.5.High HbA1c values was associated with longer duration of hospital stay (p=0.032), higher levels of inflammatory markers, increased need for mechanical ventilation (p=0.001), higher mortality rate (p=0.001).Conclusions:Patients with COVID-19 with poor glycemiccontrol as evidenced by admission HbA1c levels were found to have more severe disease course with increased level of inflammatory markers, longer duration of hospital stay and higher risk of mortality

Dose and timing of normal saline resuscitation on endothelial glycocalyx in early septic shock / 中华危重病急救医学

Objective@#To observe the effect of different doses and timing of normal saline (NS) resuscitation combined with norepinephrine (NE) on endothelial glycocalyx in rabbits with early septic shock.@*Methods@#Thirty New Zealand male rabbits were randomly divided into sham group, model group, 30 mL and 60 mL timely resuscitation groups (30 mL and 60 mL timely group), and 30 mL delayed resuscitation group (30 mL delayed group) with 6 rabbits in each group. The rabbit model of septic shock was reproduced by cecal ligation and puncture (CLP). The rabbits in sham group were only received abdominal cavity open without cecal and ligation. The rabbits in 30 mL and 60 mL timely groups and 30 mL delayed group were intravenous infused with 30 mL/kg or 60 mL/kg NS immediately or 1 hour after model reproduction for 1 hour, and the mean arterial pressure (MAP) was maintained over 75 mmHg (1 mmHg = 0.133 kPa) compared with intravenous pumping of 0.02-0.05 μg·kg-1·min-1 NE followed by 5 mL/h NS infusion till the end of the experiment. The rabbits in sham and model groups were only given 5 mL/h NS. The changes in arterial blood gas before and immediately after resuscitation were observed in three fluid resuscitation groups. The internal jugular vein blood was collected at 0, 3, 6 hours after model reproduction. The levels of syndecan-1 (polysaccharide envelope marker) in plasma were determined by enzyme linked immunosorbent assay (ELISA). The rabbits were sacrificed at 6 hours after model reproduction, and the lung tissue was harvested. Western Blot was used to determine the protein expressions of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase 2 (MMP-2) and syndecan-1. The positive expression of syndecan-1 in lung tissue was observed by immunohistochemical method.@*Results@#① Blood gas analysis: compared with the results before resuscitation, the levels of lactic acid (Lac) after resuscitation in three fluid resuscitation groups were significantly decreased, especially in 30 mL timely group; the central venous blood oxygen saturation (ScvO2) was significantly increased, especially in 30 mL delayed group. Oxygenation index (PaO2/FiO2) was improved in 30 mL timely and 30 mL delayed resuscitation groups, which was decreased in 60 mL delayed group. ② Plasma marker: compared with sham group, plasma syndecan-1 level in model group was significantly increased with a time-dependent manner. Plasma syndecan-1 levels at 3 hours in 30 mL timely and 30 mL delayed groups were significantly decreased as compared with those of model group (ng/L: 138.0±2.4, 139.7±15.7 vs. 161.5±4.1, both P < 0.05), but it was significantly increased at 6 hours in 30 mL delayed group (ng/L: 213.1±19.4 vs. 206.4±15.5, P < 0.05). The plasma syndecan-1 levels at 3 hours and 6 hours in 60 mL timely group were significantly higher than those in model group (ng/L: 233.0±28.9 vs. 161.5±4.1, 252.3±27.2 vs. 206.4±15.5, both P < 0.05). ③ Protein expression in lung tissue: compared with sham group, the protein expressions of ICAM-1 and MMP-2 in lung tissue of model group were significantly increased, and syndecan-1 protein expression was significantly decreased. After 30 mL timely or 30 mL delayed resuscitation, the protein expressions of ICAM-1 and MMP-2 in lung tissue were significantly decreased, and syndecan-1 protein expression was significantly increased, especially in 30 mL timely group, which showed statistical differences as compared with those of model group (ICAM-1 protein: 0.56±0.09 vs. 1.04±0.05, MMP-2 protein: 0.83±0.15 vs. 1.06±0.06, syndecan-1 protein: 2.09±0.08 vs. 0.99±0.03, all P < 0.05). The change tendency of protein expressions in 60 mL timely group was opposite to the other two resuscitation groups. ④ Immunohistochemistry: the positive expression of syndecan-1 in lung tissues was significant in the sham group, and it was lowered in model group. The positive expression of syndecan-1 was increased after 30 mL timely or 30 mL delayed resuscitation, but further weakened in 60 mL timely group.@*Conclusions@#The dose and timing of resuscitation with NS in septic shock can affect pulmonary vascular endothelial glycocalyx function. The timely resuscitation with 30 mL NS in combination with NE plays a protective effect on endothelial cell and glycocalyx. However, NS resuscitation which was not timely or excessive infusion can make the glycocalyx degradation more obvious, resulting in increased endothelial permeability, microcirculation damaged, thus aggravate lung injury.

Perioperative implication of the endothelial glycocalyx / 대한마취과학회지

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist's perspective.

Variation and clinical value of endothelial glycocalyx in the patients with septic shock / 中华危重病急救医学

Objective To explore the variation and clinical value of the degradation of endothelial glycocalyx in the patients with septic shock. Methods A prospective case control study was conducted. Patients of 18 years or older diagnosed with septic shock and admitted to Department of Critical Care Medicine of Affiliated Hospital of Binzhou Medical University from June 2014 to May 2015 were enrolled. The levels of degradation products, including hyaluronic acid (HA) and heparin sulfate (HS), at 0, 6, 12, 24, 48 hours were determined, while 20 healthy people were enrolled and served as controls. The changes of HA and HS were analyzed in the patients with septic shock. The differences of HA and HS between survival group and death group after 28 days were also analyzed. The relationships between HA, HS and tumor necrosis factor-α (TNF-α), sequential organ failure assessment (SOFA) score, arterial blood lactate (Lac), platelet, albumin were analyzed by Pearson correlation analysis. The receiver-operating characteristic (ROC) curve was plotted to assess the prognostic value of HA and HS for patients with septic shock. Results Thirty-one patients diagnosed as septic shock were enrolled, among whom 17 patients died after 28 days, with a mortality of 54.8%. The levels of HA and HS in patients with septic shock were increased significantly as compared with those of health control group, peaked at 48 hours, and the levels of HA and HS at 48 hours were significantly higher than those at 0 hour [HA (μg/L): 119.47±32.44 vs. 94.84±23.63, HS (μg/L): 72.83±19.03 vs. 58.83±16.63, both P < 0.05]. The levels of HA and HS at 0 hour and 48 hours in death group were significantly higher than those of the survival group [HA (μg/L): 130.42±27.67 vs. 93.29±29.80, 105.14±19.18 vs. 70.82±13.24; HS (μg/L): 67.23±25.01 vs. 39.23±14.58, 79.74±19.84 vs. 56.17±14.53, all P < 0.05]. The levels of HA and HS in patients with septic shock were remarkably positively correlated with the levels of TNF-α, SOFA score, Lac, and platelet, but were remarkably negatively correlated with albumin levels (r value of HA was 0.595, 0.462, 0.545, 0.466, -0.534, respectively; r value of HS was 0.607, 0.468, 0.563, 0.547, -0.455, respectively; all P < 0.05). It was demonstrated by ROC curves that the areas under ROC curve (AUC) of HA and HS at 0 hour and 48 hours for predicting the prognosis of patients with septic shock were 0.881, 0.940 and 0.833, 0.821, respectively, the sensitivities of HA and HS were 87.5%, 100.0% and 83.3%, 81.3%, respectively, and the specificities of HA and HS were 82.6%, 78.3% and 91.3%, 78.3%, respectively. Conclusions The concentrations of degradation products generated by endothelial glycocalyx in the blood of the patients with septic shock are remarkably increased. The elevated levels of the degradation products are closely associated with the severity of septic shock, microcirculation disturbance, and the levels of inflammatory factors.

Role of vascular endothelial glycocalyx in inflammation / 国际生物医学工程杂志

Luminal surface of vascular endothelium is decorated with a variety of polysaccharide-protein complexes,which constitute the glycocalyx.It has been demonstrated that vascular endothelial glycocalyx plays an important role in modulation of selective permeability of vessels,mediation of the blood cell-endothelial cell interactions and the release of nitric oxide induced by fluid shear stress under physiological condition.In inflammation condition,sheding of glycocalyx due to inflammation mediator leads to its functional weakening in vessel protection.At the same time,heparan sulfate as a major constituent of vascular endothelial glycocalyx could be involved in regulating the evolution of inflammation.Heparan sulfate interacts with L-selectin to mediating leukocyte rolling,presents chemokines on luminal surfaces of endothelial cells to mediate leukocyte crawling and firm adhesion,participates in transcytosis of chemokines from tissue to luminal side of endothelial cells during inflammation.Various risk factors of atherosclerosis,as an inflammatory disease,are closely associated with vascular endothelial glycocalyx.This paper is aimed to review the role of vascular endothelial glycocalyx in inflammation and atherosclerosis.