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Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality. This systematic review and meta-analysis of 19 studies was conducted to evaluate the role of copeptin in diagnosis and outcome prediction in HF patients. A systematic literature search for clinical trials reporting copeptin levels in HF patients was performed using EMBASE, PubMed, Cochrane Register of Controlled Trials, and Google Scholar. Articles from databases published by 2 January 2022, that met the selection criteria were retrieved and reviewed. The random effects model was used for analyses. Pooled analysis found higher mean copeptin levels in HF vs. non-HF populations (43.6 ± 46.4 vs. 21.4 ± 21.4; MD= 20.48; 95% CI: 9.22 to 31.74; p < 0.001). Pooled analysis of copeptin concentrations stratified by ejection fraction showed higher concentrations in HFrEF vs. HFpEF (17.4 ± 7.1 vs. 10.1 ± 5.5; MD= −4.69; 95% CI: −7.58 to −1.81; p = 0.001). Copeptin level was higher in patients with mortality/acute HF-related hospitalization vs. stable patients (31.3 ± 23.7 vs. 20.4 ± 12.8; MD= −13.06; 95% CI: −25.28 to −0.84; p = 0.04). Higher copeptin concentrations were associated with mortality and observed in all follow-up periods (p < 0.05). The present meta-analysis showed that elevated copeptin plasma concentrations observed in HF patients are associated with an increased risk of all-cause mortality, thus copeptin may serve as predictor of outcome in HF.

Stroke is the second main cause of mortality and the third leading cause of mortality and permanent disability combined. Many potential biomarkers have been described to contribute to the diagnosis, prognosis of outcomes, and risk stratification after stroke. Copeptin is an inactive peptide that is produced in an equimolar ratio to arginine vasopressin (AVP) in response to the activation of the endogenous stress system.The present study isa systematic review and meta-analysis to assess plasma copeptin concentrations, diagnostic and prognostic values for risk stratification after acute ischemic stroke and transient ischemic attack.Mean copeptin level in stroke vs. non-stroke groups varied and amounted to 19.8 ± 17.4 vs. 9.7 ± 6.6 pmol/L, respectively (mean differences [MD]: 12.75; 95% confidence interval [CI]: 5.00 to 20.49; p0.001), in good vs. poor outcome 12.0 ± 3.6 vs. 29.4 ± 14.5 (MD: -8.13; 95% CI: -8.37 to -7.88; p0.001) and in survive vs. non-survive stroke patients: 13.4 ± 3.2 vs. 33.0 ± 12.3, respectively (MD: -13.43; 95% CI: -17.82 to -9.05; p0.001).The above systematic review and meta-analysis suggests that monitoring the copeptin levels may help predict the long-term prognosis of ischemic stroke efficiently. Determining the copeptin level may help individualize the management of ischemic stroke patients, keep stroke risk lower, reduce post-stroke complications, including patient death, and minimize healthcare costs.

Background: Vitamin D is a likely candidate for treatment as its immune modulating characteristics have effects on coronavirus disease 2019 (COVID-19) patients. It was sought herein, to summarize the studies published to date regarding the vitamin D supplementation to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive patients. Methods: A systematic review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome were 14-day and in-hospital mortality reported as an odds ratio (OR) with the associated 95% confidence interval (CI). Results: Eight articles were included in the review with a combined total of 2,322 individual patients, 786 in the vitamin D supplementation group and 1,536 in the control group. The use of vitamin D compared to the group without vitamin D supplementation was associated with a lower 14-day mortality (18.8% vs. 31.3%, respectively; OR = 0.51; 95% CI: 0.12–2.19; p = 0.36), a lower in-hospital mortality (5.6% vs. 16.1%; OR = 0.56; 95% CI: 0.23–1.37; I 2 = 74%; p = 0.20), the rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06–0.54; I 2 = 77%; p = 0.002) as well as rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16–0.80; I 2 = 0.48; p = 0.01). Conclusions: Vitamin D supplementation in SARS-CoV-2 positive patients has the potential to positively impact patients with both mild and severe symptoms. As several high-quality randomized control studies have demonstrated a benefit in hospital mortality, vitamin D should be considered a supplemental therapy of strong interest. Should vitamin D prove to reduce hospitalization rates and symptoms outside of the hospital setting, the cost and benefit to global pandemic mitigation efforts would be substantial.

The most common cause of potentially preventable trauma deaths is hemorrhage. Therefore, it is crucial to understand the mechanisms regulating bleeding and clotting. The physiological mechanisms that control the coagulation process are called the coagulation cascade. In this study, we analyzed the medical literature for published articles on the use of TXA for bleeding. The MEDLINE electronic database was searched for. The keywords we have used were: “tranexamic acid”, “bleeding”, “hemorrhage”, “treatment”, “prevention”, “patient blood management”, “anti-fibrinolytic”, “surgery”, “surgery”, “trauma”, “injury” and “traumatic brain injury”. When managing the traumatic patient, time is of the essence and the same holds true for the TXA application. The largest study regarding the use of TXA in the emergency medicine CRASH-2 found that the administration of TXA within 3 hours following injury significantly reduces the mortality and that every 15-min delay in administering TXA results in increased bleeding and decreased survival by 10%, offering no benefit if administered after 3 hours. In summary, TXA is a safe and reliable agent which greatly increases the survival rate in traumatic patients suffering blood loss, reducing mortality while being safe.

Background: Coronary artery aneurysms (CAA) are infrequent findings among patients undergoing coronary angiography and may be associated with systemic diseases. Methods: We analyzed the National Inpatient Sample database from 2016 to 2020 by including all patients with the admission diagnosis of the chronic coronary syndrome (CCS). We sought to determine the impact of CAA on in-hospital outcomes encompassing all-cause death, bleeding, cardiovascular complications, and stroke. Secondly, we examined the association of CAA with other relevant systemic conditions. Results: The presence of CAA was associated with a 3-fold increase in the odds of cardiovascular complications (OR 3.1, 95 % CI 2.9-3.8), however, it was associated with reduced odds of stroke (OR 0.7, 95 % CI 0.6-0.9). There was no significant impact on all-cause death and overall bleeding complications, although there appeared to be a reduction in the odds of gastrointestinal (GI) bleeding associated with CAA (OR 0.6, 95 % CI 0.4-0.8). Patients with CAA vs. those without CAA had a significantly greater prevalence of extracoronary arterial aneurysms (7.9 % vs. 1.4 %), systemic inflammatory disorders (6.5 % vs. 1.1 %), connective tissue disease (1.6 % vs. 0.6 %), coronary artery dissection (1.3 % vs. 0.1 %), bicuspid aortic valve (0.8 % vs. 0.2 %), and extracoronary arterial dissection (0.3 % vs. 0.1 %). In the multivariable regression, systemic inflammatory disorders, extracoronary aneurysms, coronary artery dissection, and connective tissue diseases were independent predictors of CAA. Conclusions: CAA in patients with CCS is associated with greater odds of cardiovascular complications during hospitalization. These patients also had a substantially greater prevalence of extracardiac vascular and systemic abnormalities.

Studying the structural dynamics of lipid membranes requires methods that can address both microscopic and macroscopic characteristics. Fluorescence imaging is part of the most used techniques to study membrane properties in various systems from artificial membranes to cells: It benefits from a high sensitivity to local properties such as polarity and molecular orientational order, with a high spatial resolution down to the single-molecule level. The influence of embedded fluorescent lipid probes on the lipid membrane molecules is however poorly known and relies most often on molecular dynamics simulations, due to the challenges faced by experimental approaches to address the molecular-scale dimension of this question. In this work we develop an optical microscopy imaging method to probe the effect of fluorophores embedded in the membrane as lipid probes, on their lipid environment, with a lateral resolution of a few hundreds of nanometers. We combine polarized-nonlinear microscopy contrasts that can independently address the lipid probe, by polarized two-photon fluorescence, and the membrane lipids, by polarized coherent Raman scattering. Using trimethylamino derivative 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate (di-8-ANEPPS) as model probes, we show that both probes tend to induce an orientational disorder of their surrounding lipid CH-bonds in 1,2-dipalmitoylphosphatidylcholine (DPPC) lipids environments, while there is no noticeable effect in more disordered 1,2-dioleoyl

Background: Coronavirus disease 2019 (COVID-19) is a disease primarily affecting the respiratory tract, however due to the nature of the pathogenesis it is able to affect the whole body. So far, no causative treatment has been found and the main strategy when dealing with COVID-19 relies on widespread vaccination programs and symptomatic treatment. Vitamin D due to its ability to modulate the immunological system has been proposed as a factor playing role in the organism response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, we decided to perform this meta-analysis which aimed to establish a connection between vitamin D status and COVID-19 infection. Methods: Study was designed as a systematic review and meta-analysis. PubMed, EMBASE, Web of Science, Cochrane Collaboration Databases and Scopus electronic databases were searched for relevant studies from database inception to May 10th, 2021. Mean differences (MDs) with their 95% confidence intervals (CI) were calculated. Results: Thirteen studies providing data for 14,485 participants met the inclusion criteria. Mean vitamin D levels in SARS-CoV-2 negative patients was 17.7 ± 6.9 ng/mL compared to SARS-CoV-2 positive patients 14.1 ± 8.2 ng/mL (MD = 3.93; 95% CI 2.84–5.02; I2 = 99%; p < 0.001). Conclusions: Low serum vitamin D levels are statistically significantly associated with the risk of COVID-19 infection. Supplementation of vitamin D especially in the deficiency risk groups is indicated.

Background Ischemic stroke (IS) is one of the most frequent causes of death. Since miRNAs have been illustrated to play an important role in various processes through regulation of multiple genes, and platelet function, their utility as novel biomarkers should be determined. Purpose We aimed to analyze the circulating platelet-derived miR-19a-3p, miR-186-5p, Let-7f, platelet-extracellular vesicles (EVs), leukocyte-EVs, and endothelial-EVs levels 24-h and 7-days after IS as novel diagnostic and prognostic/predictive biomarkers in 28 acute IS and 35 control patients. Methods Blood samples of 28 patients diagnosed with acute IS with hyper platelet reactivity were collected 24-h and 7-days after stroke and 35 age- and gender-matched individuals free of stroke with multiple risk factors for cardiovascular disease. Platelet reactivity was assessed by AA-, TRAP-, ADP-induced platelet aggregometry. PlasmaRNA was extracted; quality RNA was assessed: fluorometric assay; RT-PCR for miRNAs expression measurement and flow-cytometry for EVs determination p Results Patients with IS on day-1 had significantly higher platelet reactivity assessed by AA-induced platelet aggregometry compared to controls (p=0.001). Patients with normal platelet activation had significantly higher miR-186-5p expression levels compared to patients with HPR at day-1 acute-stroke (p=0.034). Seven days after acute stroke, expression levels of miR-186-5p significantly decreased in the same patients with normal platelet reactivity (p=0.036). Patients with HPR had significantly elevated platelet-EVs (CD62) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p=0.012). Similarly, patients with HPR had significantly higher leukocyte-EVs (CD45) concentration compared to patients with normal platelet function at day-1 acute-stroke (p=0.002). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic curve analysis. ROC curve showed that pooling the miR-19a-3p expressions, platelet-EVs, and leukocyte-EVs concentration yielded a higher AUC than the value of each individual biomarker as AUC was 0.893 (95% CI, 0.79–0.99). Patients with moderate stroke had significantly elevated miR-19a-3p expression levels compared with patients with minor stroke at the day of acute IS. AUC in ROC curve analysis was 0.867, (95% CI, 0.74–0.10) p=0.001. Conclusions Our analysis showed alteration of circulating miRNAs and EVs after IS. Combination of miR-19a-3p, Let-7f, platelet-EVs and leukocyte-EVs might have a diagnostic value for acute stroke and miR-19a-3p can predict the severity of stroke in IS patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Centre - Narodowe Centrum Nauki

Background Transcatheter aortic valve implantation (TAVI) is a novel treatment for aortic stenosis (AS), associated with better outcomes than surgical aortic valve replacement in high-risk patients. However, up to 29% of patients annually experience major adverse cardiac and cerebrovascular events (MACCE) after TAVI. MACCE are mostly caused by atherothrombosis, i.e. formation of platelet aggregates (thrombi) on ruptured atherosclerotic plaques. Because platelets release extracellular vesicles (EVs) during thrombus formation, we hypothesized that EVs are a biomarker to predict MACCE after TAVI. Methods This was a multicentre, prospective clinical study. Venous blood was collected 1 day before TAVI and at hospital discharge (n=57, mean age 79.9+6.4 years, 49% male). Flow cytometry (Apogee A60-Micro) was used to determine concentrations of plasma EVs labelled with markers for endothelial cells (CD146), leukocytes (CD45), platelets and megakaryocytes (CD61) and activated platelets (CD62p). Analysis of flow cytometry data files was fully automated. Rosetta Calibration (Exometry) and Flow-SR were used for diameter and refractive index determination. Wilcoxon signed rank test was used to compare EV concentrations before and after TAVI. The predictive value of EVs for MACCE and the cut-offs were calculated using a receiver operating characteristic curve. Logistic regression model incorporating EV concentrations and clinical characteristics was used to determine the best model for MACCE prediction. Results Concentrations of EVs from activated platelets increased, whereas from leukocytes decreased after TAVI, compared to the measurement before (p=0.06, p=0.04, respectively). Among 55 patients discharged from the hospital, 14 patients experienced MACCE (25%) during the median 15 months of observation. Increased baseline concentration of leukocyte EVs and male gender were the only independent predictors of MACCE in multivariable analysis (OR 4.01, 95% CI 0.77–23.77, p=0.04 for leukocyte EVs; OR 6.84, 95% CI 1.41–33.17, p=0.03 for male gender). Conclusions We identified increased concentrations of leukocyte EVs as new candidate biomarkers to predict MACCE after TAVI. Leukocyte EVs could be used to augment risk stratification in this patient cohort. The next step is to validate the clinical applicability of EVs to predict post-TAVI MACCE in a large-scale clinical trial. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Young Investigator Grant of the Polish Society of Cardiology

Background Acute coronary syndrome (ACS), which comprises acute myocardial infarction (AMI) and unstable angina pectoris (UAP), is one of the main causes of mortality worldwide. Cardiac troponin is the gold standard to diagnose AMI. Troponin has two main disadvantages: it is negative in patients with UAP but positive in other diseases. During ACS, activated platelets release extracellular vesicles (EVs), which promote coagulation and associate with fibrin, and contribute to thrombus formation. We hypothesized that the concentration and composition of circulating platelet EVs (1) change in blood of patients with ACS compared to patients with other causes of chest pain, and (2) thereby allow earlier diagnosis of ACS than cardiac troponin. Purpose We aimed to determine the diagnostic value of circulating platelet EVs as novel early biomarkers of developing ACS. Methods We conducted a prospective, multicentre trial enrolling 105 patients who presented to the emergency department with suspected ACS. Blood was collected at admission to measure the concentration of EVs and cardiac troponin. Flow cytometry (Apogee A60-Micro) was used to determine plasma concentrations of platelet EVs exposing P-selectin (CD61+/CD62p+) and fibrin (CD61+/fibrin+). Results Plasma concentrations of platelet EVs exposing fibrin was lower in patients with ACS, compared to patients with other causes of chest pain (p=0.023) and lower in patients with an occlusive thrombus compared to non-occlusive plaque (p=0.015). Fibrin exposing-EVs were independent predictors of ACS (OR 8.2, CI 1.3–16.4) in multivariate analysis, allowing to diagnose ACS with 75% sensitivity and 72% specificity. Among patients with pain onset less than 2 hours before presentation, fibrin-exposing EVs had substantially better diagnostic performance than troponin (area under the ROC curve 0.90 vs. 0.74, respectively). Regarding other causes of chest pain, fibrin-exposing EVs were the lowest in patients with ACS, higher in patients with other cardiological causes of chest pain, and the highest in patients with non-cardiological causes of chest pain (p=0.036). Conclusions Circulating fibrin-exposing EVs are early biomarkers of developing ACS, superior to cardiac troponin in patients with pain onset less than 2 hours before presentation. Incorporation of EV measurements into the ACS diagnostic algorithm might revolutionise thrombotic risk stratification in the emergency setting. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Specialised Research Fellowship, “Club 30” of the Polish Society of Cardiology

Background: Long-term results after stenting aorto-coronary ostial lesions (AOL) are worse than those achieved in non-ostial locations. AOL interventions still pose a substantial challenge for interventional cardiologists. The aim of the study was to determine the optimal fluoroscopic viewing angles of the left and right coronary ostia, based on multislice computed tomography (MSCT) data. Methods: Cardiac MSCT exams of 30 patients with clinical suspicion of coronary artery disease were analyzed. En face angles of both coronary ostia, as well as their optimal projection curves, were determined by 2 independent observers in a standard Dicom viewer, without any additional, specialized software add-ons, using a systematic, step-by-step approach. Spatial relations between the ostial plane and the aorta were also assessed. Results: The average en face angle of the left coronary ostium was RAO 23°, CAU 45°; for the right coronary ostium RAO 18°, CRA 5°. The mean inter-observer differences for the en face angles of the left and right coronary arteries were 5° and 7°, respectively. Conclusion: Multislice computed tomography data provide precise spatial information on the orientation of the coronary ostia and their relation to the aortic root. Their utilization for determining the patient-specific viewing angle may substantially facilitate percutaneous coronary interventions in AOL.

Massive bleedings, both internal and external, are among the leading causes of preventable deaths. The research for the appropriate treatment focuses not only on looking for the new drugs but also relies on finding the new indications for the drugs already known in the pharmacotherapy of different disease. However, such an approach requires new protocols in order to be effective. One of the substances in question is tranexamic acid, which uses due to its antifibrinolytic effect is raising both in prehospital and hospital settings.

Background Blood plasma is commonly used for biomarker research of extracellular vesicles (EVs). Removing all cells prior to analysis of EVs is essential. Objectives We therefore studied the efficacy of the most commonly used centrifugation protocol to prepare cell-free plasma. Methods Plasma was prepared according to the double centrifugation protocol of the International Society on Thrombosis and Haemostasis (ISTH) in three independent studies. The concentrations of platelets, platelet-derived EVs, and erythrocyte-derived EVs were measured by calibrated flow cytometry. Results The mean platelet concentration ranged from 5.1 x 10(5)/ml to 2.8 x 10(7)/ml and differed 55-fold between studies. Thus, the ISTH centrifugation protocol does not remove all platelets and results in variation between studies. As the concentration of platelet-derived EVs and platelets correlates linearly (R-2 = .56), and the volume fraction of EVs and platelets in plasma are similar, the presence of platelets affects downstream analysis. To remove platelets a 0.8-mu m polycarbonate filter was used to lower the platelet concentration 146-fold (p = .0013), without affecting the concentration of platelet-derived and erythrocyte-derived EVs (p = .982, p = .742). Conclusions To improve the quality of EV research, we recommend (1) measuring and reporting the platelet concentration in plasma used for EV research, or (2) removing platelets by centrifugation followed by filtration.

Therapeutic hypothermia, or targeted temperature management (TTM), is a strategy of reducing the core body temperature of survivors of sudden cardiac arrest, cardiogenic shock (CS) or stroke. Therefore, a systematic literature review and meta-analysis were performed to tackle the question about whether the implementation of TTM is actually beneficial for patients with CS.Study was designed as a systematic review and meta-analysis. PubMed, Cochrane Library, Web of Science and Scopus were searched from these databases inception to July 17, 2022. Eligible studies were those comparing TTM and non-TTM treatment in CS patients. Data were pooled with the Mantel-Haenszel method.Thirty-day mortality was reported in 3 studies. Polled analysis of 30-day mortality was 44.2% for TTM group and 48.9% for non-TTM group (risk ratio: 0.90; 95% confidence interval: 0.75 to 1.08; p = 0.27). Other mortality follow-up periods showed also no statistically significant differences (p0.05). The occurrence of adverse events in the studied groups also did not show statistically significant differences between TTM and non-TTM groups (p0.05 for myocardial infarction, stent thrombosis, sepsis, pneumonia, stroke or bleeding events).The present analysis shows no significant benefit of TTM in patients with CS. Moreover, no statistically significant increase of the incidence of adverse effects was found. However, further randomized studies with higher sample size and greater validity are needed to determine if TTM is worth implementing in CS patients.