Monitoring the Coagulation Profile of COVID-19 Patients Using Standard and ClotPro® Hemostasis Tests.

Background and Objectives: Coagulation disorders during COVID-19 infection are associated with a poorer prognosis and higher disease severity because thrombosis and inflammation are two processes that interfere with each other. A very important issue for clinicians is timely and adequate hemostasis and inflammation monitoring to prevent and treat potentially lethal consequences. The aim of this study was to identify specific hemostatic parameters that are associated with a higher risk of intrahospital mortality. Materials and Methods: This study was approved by the Ethics Committee of the Clinical Center Nis in Serbia. One hundred and forty-two patients presented with COVID-19 ARDS and were admitted to the ICU in the Clinic for Anesthesiology at the Clinical Center Nis from 14 April 2020 to 25 May 2020. Upon admission, blood was collected for biochemical and coagulation testing. The data obtained were analyzed using the Statistical Package for Social Sciences (SPSS v. 25, Chicago, IL, USA). Results: Among all the parameters assessed, older age; increased levels of fibrinogen, INR, D-dimer, and presepsin; and higher results in the platelet aggregation tests (aggregation induced by adenosine diphosphate based on the ADP test (AU/min), aggregation induced by arachidonic acid based on the ASPI test (AU/min), and aggregation induced by thrombin based on the TRAP test (AU/min)) and some assays of the viscoelastic test (clot amplitude after 5 min in the extrinsic coagulation pathway based on the A5 EX-test (mm), clot amplitude after 10 min in the extrinsic coagulation pathway based on the A10 EX-test (mm), clot amplitude after 5 min regarding functional fibrinogen based on the A5 FIB-test (mm), clot amplitude after 10 min regarding functional fibrinogen based on the A10 FIB-test (mm), and maximum clot firmness based on the MCF FIB-test (mm)); and lower values of viscoelastic clotting time in the extrinsic coagulation pathway based on the CT EX-test (s) were significantly correlated with mortality. In the multivariate analysis, D-dimer levels above 860 ng/mL, higher TRAP test value bins, and values above the normal reference range of the A10 FIB test were found to be independent predictors of mortality. Conclusions: Sophisticated hemostasis parameters can contribute to early risk assessment, which has initially been performed only on the basis of patients' clinical status. Hypercoagulability is the main coagulation disorder in COVID-19 infection.

Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery.

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

In silico development of potential therapeutic for the pain treatment by inhibiting voltage-gated sodium channel 1.7.

The voltage-gated sodium channel Nav1.7 can be considered as a promising target for the treatment of pain. This research presents conformational-independent and 3D field-based QSAR modeling for a series of aryl sulfonamide acting as Nav1.7 inhibitors. As descriptors used for building conformation-independent QSAR models, SMILES notation and local invariants of the molecular graph were used with the Monte Carlo optimization method as a model developer. Different statistical methods, including the index of ideality of correlation, were used to test the quality of the developed models, robustness and predictability and obtained results were good. Obtained results indicate that there is a very good correlation between 3D QSAR and conformation-independent models. Molecular fragments that account for the increase/decrease of a studied activity were defined and used for the computer-aided design of new compounds as potential analgesics. The final evaluation of the developed QSAR models and designed inhibitors were carried out using molecular docking studies, bringing to light an excellent correlation with the QSAR modeling results.

Preoperative Levels of the Soluble Urokinase-Type Plasminogen Activator Receptor as Predictor for New Episodes of Atrial Fibrillation After Vascular Surgery.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) in uPAR soluble form is produced when the uPAR is cleaved from the cell membrane during the inflammatory process. Postoperative atrial fibrillation (AF) is the most common perioperative cardiac arrhythmia. It is speculated that elevated suPAR has a role in the development of AF. The aim of our study was to investigate the predictive role of preoperative suPAR in the occurrence of AF during the first 6 months after major vascular surgery. METHODS: We included 119 male and 63 female patients with an average age of 67.19 ± 6.02 years, without permanent/persistent AF. Basic predictive model (BASIC) included traditional risk factors for AF: age, gender, body mass index-BMI, smoking status, presence of arterial hypertension, diabetes mellitus and dyslipidemia. RESULTS: Over the 6-month period, 19 (10.4%) patients had one new episode of atrial fibrillation and 2 patients (1.1%) had 2 episodes of paroxysmal atrial fibrillation. Paroxysms of AF were significantly more frequent in patients who had a resection of an abdominal aneurysm than in patients with other types of major vascular surgery. BASIC had good discriminatory ability in the prediction of AF paroxysms during the first 6 months after surgery (AUC = 0.715, 95%CI 0.590-0.840). Adding suPAR to the basic model significantly improved the discriminative ability of the predictive model for AF episodes (ΔAUC = 0.238, p < 0.001). The predictive performance of the model BASIC+CRP+suPAR, measured using AUC, NRI and IDI statistics, was very similar to the model BASIC+suPAR. CONCLUSION: AF is a common complication in surgical patients with high mortality and morbidity. suPAR could improve the ability of traditional risk factors to predict its occurrence up to 6 months after major vascular surgery.

Potential New Approaches in Predicting Adverse Cardiac Events One Month after Major Vascular Surgery.

OBJECTIVE: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. SUBJECTS AND METHODS: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. RESULTS: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. CONCLUSION: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.

A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.