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Background: Increased inflammation activates blood coagulation system, higher platelet activation plays a key role in the pathophysiology of ischemic stroke (IS). During platelet activation and aggregation process, platelets may cause increased release of several proinflammatory, and prothrombotic mediators, including microRNAs (miRNAs) and extracellular vesicles (EVs). In the current study we aimed to assess circulating miRNAs profile related to platelet function and inflammation and circulating EVs from platelets, leukocytes, and endothelial cells to analyse their diagnostic and predictive utility in patients with acute IS. Methods: The study population consisted of 28 patients with the diagnosis of the acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid (ASA) therapy without history of stroke and/or TIA with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors. Venous blood samples were collected from the control group and patients with IS on ASA therapy (a) 24 h after onset of acute IS, (b) 7-days following index hospitalization. Flow cytometry was used to determine the concentration of circulating EVs subtypes (from platelets, leukocytes, and endothelial cells) in platelet-depleted plasma and qRT-PCR was used to determine several circulating plasma miRNAs (miR-19a-3p, miR-186-5p and let-7f). Results: Patients with high platelet reactivity (HPR, based on arachidonic acid-induced platelet aggregometry) had significantly elevated platelet-EVs (CD62+) and leukocyte-EVs (CD45+) concentration compared to patients with normal platelet reactivity at the day of 1 acute-stroke (p = 0.012, p = 0.002, respectively). Diagnostic values of baseline miRNAs and EVs were evaluated with receiver operating characteristic (ROC) curve analysis. The area under the ROC curve for miR-19a-3p was 0.755 (95% CI, 0.63–0.88) p = 0.004, for let-7f, it was 0.874 (95% CI, 0.76–0.99) p = 0.0001; platelet-EVs was 0.776 (95% CI, 0.65–0.90) p = 0.001, whereas for leukocyte-EVs, it was 0.715 (95% CI, 0.57–0.87) p = 0.008. 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 to patients with minor stroke at the first day of IS. (AUC: 0.867, (95% CI, 0.74–0.10) p = 0.001). Conclusion: Combining different biomarkers of processes underlying IS pathophysiology might be beneficial for early diagnosis of ischemic events. Thus, we believe that in the future circulating biomarkers might be used in the prehospital phase of IS. In particular, circulating plasma EVs and non-coding RNAs including miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in the blood and making them highly relevant biomarkers for IS diagnostics. [ABSTRACT FROM AUTHOR]

Background: The novel coronavirus disease 2019 (COVID-19) has spread worldwide since the beginning of 2020, placing the heavy burden on the health systems all over the world. The population that particularly has been affected by the pandemic is the group of patients suffering from diabetes mellitus. Having taken the public health in considerations, we have decided to perform a systematic review and meta-analysis of diabetes mellitus on in-hospital mortality in patients with COVID-19. Methods: A systematic literature review (MEDLINE, EMBASE, Web of Science, Scopus, Cochrane) including all published clinical trials or observational studies published till December 10, 2020, was performed using following terms "diabetes mellitus" OR "diabetes" OR "DM" AND "survival" OR "mortality" AND "SARS-CoV-2" OR "COVID-19". Results: Nineteen studies were included out of the 7327 initially identified studies. Mortality of DM patients vs non-DM patients was 21.3 versus 6.1%, respectively (OR = 2.39; 95%CI: 1.65, 3.64; P < 0.001), while severe disease in DM and non-DM group varied and amounted to 34.8% versus 22.8% (OR = 1.43; 95%CI: 0.82, 2.50; P = 0.20). In the DM group, the complications were observed far more often when compared with non-DM group, both in acute respiratory distress (31.4 vs. 17.2%; OR = 2.38; 95%CI:1.80, 3.13; P < 0.001), acute cardiac injury (22.0% vs. 12.8%; OR = 2.59; 95%CI: 1.81, 3.73; P < 0.001), and acute kidney injury (19.1 vs. 10.2%; OR = 1.97; 95%CI: 1.36, 2.85; P < 0.001). Conclusions: Based on the findings, we shall conclude that diabetes is an independent risk factor of the severity of COVID-19 in-hospital settings; therefore, patients with diabetes shall aim to reduce the exposure to the potential infection of COVID-19. [ABSTRACT FROM AUTHOR]

This study investigated concentration changes of dissolved and particulate organic carbon in a meromictic lake to determine the lake's productivity. It was revealed that the dominant form of organic carbon was the dissolved form (DOC). Maximum production activity was observed in summer (with the peak in June). At the same time, the factors restricting that process were determined, such as: strong pressure of the bacteria competing with the phytoplankton for mineral nutrients, and simultaneous precipitation of phosphates on HS-Fe complexes. The generated organic matter was settling intensively, and one of the transport methods of the dissolved organic matter was adsorption on calcium carbonate and bacterial transformation of the part of DOC into POC. [ABSTRACT FROM AUTHOR]

Background: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel., Objectives: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel., Methods: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors., Results: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor., Conclusions: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: 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., Methods: 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., Results: 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 (p > 0.05). The occurrence of adverse events in the studied groups also did not show statistically significant differences between TTM and non-TTM groups (p > 0.05 for myocardial infarction, stent thrombosis, sepsis, pneumonia, stroke or bleeding events)., Conclusions: 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.

Background: Statin use in many studies is related to the improvement of a patients' condition including reducing the risk of various malignancies. Herein, is a systematic review and meta-analysis to examine the evidence on the association between statin therapy and the risk of the occurrence of pancreatic cancer, mainly in terms of decreased risk of developing pancreatic cancer among patients using statin therapy in the long-term perspective., Methods: PubMed, Web of Science, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database inception to December 1st, 2021. Random effect models were used to estimate summary odds ratios (OR) and the corresponding 95% confidence intervals (CI)., Results: A total of 26 studies comprising 2,797,186 patients were included. Polled analysis showed that pancreatic cancer occurrence in statin vs. no-statin group varied and amounted to 0.4% vs. 0.6% (RR = 0.83; 95% CI: 0.72-0.96; I² = 84%; p = 0.01)., Conclusions: In summary, the present analysis shows that overall statins use is significantly associated with a reduction in risk of pancreatic cancer. However, these results were not confirmed for the randomized controlled trial subgroup. Further prospective studies are needed to confirm the current results.

Background: In contemporary clinical practice, there is an increasing need for new clinically relevant biomarkers potentially optimizing management strategies in patients with suspected acute coronary syndrome (ACS). This study aimed to determine the diagnostic utility of soluble urokinase-type plasminogen activator receptor (suPAR) levels in individuals with suspected ACS., Methods: A literature search was performed in Web of Science, PubMed, Scopus, and the Cochrane Central Register of Controlled Trials databases, for studies comparing suPAR levels among patients with and without ACS groups. The methodological quality of the included papers was assessed using the Newcastle-Ottawa Scale (NOS). A fixed-effects model was used if I² < 50%; otherwise, the random-effects model was performed., Results: Five studies with 3417 participants were included in the meta-analysis. Pooled analysis showed that mean suPAR levels in the ACS group were statistically significantly higher than in the control group (3.56 ± 1.38 vs. 2.78 ± 0.54 ng/mL, respectively; mean difference: 1.04; 95% confidence interval: 0.64-1.44; I² = 99%; p < 0.001)., Conclusions: In the context of acute coronary syndrome, suPAR is a potential biomarker for the early identification of medical conditions in individuals who are being treated in emergency rooms.

Antiplatelet therapy is a cornerstone of secondary prevention of cardiovascular diseases (CVDs). However, current guidelines are based on data derived primarily from men, as women are generally underrepresented in trials. Consequently, there are insufficient and inconsistent data on the effect of antiplatelet drugs in women. Sex differences were reported in platelet reactivity, patient management, and clinical outcomes after treatment with aspirin, P2Y 12 inhibitor, or dual antiplatelet therapy. To evaluate whether sex-specific antiplatelet therapy is needed, in this review we discuss (i) how sex affects platelet biology and response to antiplatelet agents, (ii) how sex and gender differences translate into clinical challenges and (iii) how the cardiological care in women might be improved. Finally, we highlight the challenges faced in clinical practice regarding the different needs and characteristics of female and male patients with CVD and address issues requiring further investigation.

Introduction and Objective: The global impact of acute kidney injury (AKI) has not been thoroughly investigated. With the development of new techniques, soluble urokinase plasminogen activator receptor (suPAR) has become increasingly important in the diagnosis of AKI. Therefore, a systematic review and meta-analysis was carried out to evaluate the predictive value of suPAR for AKI., Material and Methods: The review and meta-analysis investigated the relationship between suPAR levels and acute kidney injury. Pubmed, Scopus, Cochrane Controlled Register of Trials, and Embase were searched for relevant studies from inception to 10 January 2023. Stata (Ver. 16 StataCorp, College Station, TX, USA) was used for all statistical analyses. A random effects model using the Mantel-Haenszel approach was employed, and odds ratios (OR) and standard mean differences (SMD) with 95% confidence intervals (CI) were calculated for binary and continuous outcomes, respectively., Results: Nine studies reported suPAR levels among patients with and without AKI. Pooled analysis showed that suPAR levels in patients with and without AKI varied and amounted to 5.23 ± 4.07 vs. 3.23 ±0.67 ng/mL (SMD = 3.19; 95%CI: 2.73 to 3.65; p<0.001). The results from the sensitivity analysis did not alter the direction., Conclusions: This results show that increasing suPAR levels are associated with the occurrence of AKI. SuPAR might act as a novel biomarker for CI-AKI in clinical practice.

Glycoprotein IIb/IIIa inhibitors are an adjuvant therapy for the treatment of patients with acute coronary syndromes. The main adverse reactions are bleeding and thrombocytopenia in 1-2% of cases. A 66-year-old woman arrived at the emergency department with ST-elevation MI. The catheterisation lab was busy, so she received thrombolytic therapy. Coronary angiography revealed a 90% stenosis in the middle segment of the left anterior descending artery and Thrombolysis in MI 2 flow. Subsequent percutaneous coronary intervention showed abundant thrombus and a coronary dissection and it was necessary to insert five drug-eluting stents. Non-fractionated heparin and a tirofiban infusion were used. After the percutaneous coronary intervention, she developed severe thrombocytopenia, haematuria and gingivorrhagia, for which infusion of tirofiban was suspended. In follow-up, no major bleeding or subsequent haemorrhagic complications were identified. It is crucial to distinguish between heparin-induced thrombocytopenia and thrombocytopenia caused by other drugs. A high level of suspicion should be employed in these cases., Competing Interests: Disclosure: The authors have no conflicts of interest to declare. Consent: Written informed consent was obtained from all individuals included in the study. Ethics: This document was reviewed by the local bioethics committee and was approved., (Copyright © 2023, Radcliffe Cardiology.)

Introduction and Objective: In COVID-19, the rapid prediction of the severity of a patient's condition using modern biomarkers can accelerate the implementation of appropriate therapy, and thus improve the patient's prognosis., Material and Methods: A meta-analysis was conducted of data available in the literature on the differences in baseline suPAR blood concentration between patients (1) who tested positive and negative for COVID-19, (2) who had severe and non-severe COVID-19, and (3) COVID-19 survivors and non-survivors., Results: SuPAR levels in SARS-CoV-2 negative and positive patients varied and amounted to 3.61±1.59 ng/ml vs. 6.45±3.13 ng/ml, respectively (MD = -3.18; 95%CI: -4.71 to -1.66; p<0.001). suPAR levels among non-severe and severe COVID-19 patients were 7.06±2.64 ng/ml and 5.06±3.16 ng/ml (MD = 0.18; 95%CI: -2.48 to 2.83; p=0.90), respectively. Pooled analysis showed that suPAR levels between severe versus critical COVID-19 patients to be 5.59±1.54 ng/ml and 6.49±1.43 ng/ml, respectively (MD = -1.00; 95%CI: -1.31 to -0.70; p<0.001). The suPAR levels between ICU survivors versus non-survivors amounted to 5.82±2.33 ng/ml and 8.43±4.66 ng/ml (MD = -3.59; 95%CI: -6.19 to -1.00; p=0.007). In the case of in-hospital mortality, the mean suPAR level among survivors to hospital discharge was 5.63±1.27 ng/ml, compared to 7.85±2.61 ng/ml for patients who did not survive (MD = -3.58; 95%CI: -5.42 to -1.74; p<0.001)., Conclusions: SuPAR levels are significantly elevated in severe COVID-19 illness and maybe useful in predicting mortality. Further studies are needed to determine cut-off points and clarify the association of suPAR levels with disease progression. This is of utmost importance given the ongoing pandemic and overburdened health care systems.

Pulmonary embolism (PE) is the third leading cause of cardiovascular death in the western world. Prompt recognition, risk stratification, and individualized treatment are crucial to improve outcomes in patients with PE. Anticoagulation alone is a sufficient therapeutic option in low-risk patients, whereas primary reperfusion with systemic thrombolysis (ST) is usually chosen in high-risk patients. The choice of treatment in intermediate-risk patients is complex and depends on the clinical presentation. Catheter-directed therapy (CDTh) includes all therapies delivered via a catheter placed in the branches of the pulmonary arteries directly into the thrombus. Because ST bears a high risk of major bleeding and numerous patients have contraindications to ST, CDTh is an alternative to ST in intermediate- and high-risk PE patients. CDTh includes local thrombolysis using low-dose alteplase, ultrasound-assisted thrombolysis, and mechanical fragmentation and aspiration of the thrombi, as well as their combinations. In this review article, we have summarized devices and technical details for CDTh, discussed the efficacy and safety of CDTh in comparison to ST in previous clinical trials, and outlined future research directions regarding CDTh, both based on the literature and our personal experience from the local PE Response Team of the Center for the Management of Pulmonary Embolism (CELZAT) in Warsaw.

Background: Echocardiography in the setting of resuscitation can provide information as to the cause of the cardiac arrest, as well as indicators of futility. This systematic review and meta-analysis were performed to determine the value of point-of-care ultrasonography (PoCUS) in the assessment of survival for adult patients with cardiac arrest., Methods: This meta-analysis was performed in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, EMBASE, Web of Science, Cochrane have been searched from databases inception until March 2nd 2021. The search was limited to adult patients with cardiac arrest and without publication dates or country restrictions. Papers were chosen if they met the required criteria relating to the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of this diagnostic technique concerning resuscitation outcomes., Results: This systematic review identified 20 studies. Overall, for survival to hospital discharge, PoCUS was 6.2% sensitivity (95% confidence interval [CI] 4.7-8.0%) and 2.1% specific (95% CI 0.8-4.2%). PoCUS sensitivity and specificity for return of spontaneous circulation were 23.8% (95% CI 21.4-26.4%) and 50.7% (95% CI 45.8-55.7%) respectively, and for survival to admission 13.8% (95% CI 12.2-15.5%) and 20.1% (95% CI 16.2-24.3%), respectively., Conclusions: The results do not allow unambiguous recommendation of PoCUS as a predictor of resuscitation outcomes and further studies based on a large number of patients with full standardization of operators, their training and procedures performed were necessary.

Background: According to the guidelines of cardiopulmonary resuscitation (CPR) conducted by bystanders, two methods of CPR are feasible: standard CPR (sCPR) with mouth-to-mouth ventilations and continuous chest compression-only CPR (CCC) without rescue breathing. The goal herein, was to evaluate the effect of sCPR (30:2) and CCC on resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA) patients., Methods: This study was a systematic review and meta-analysis. Using standardized criteria, Pub- Med, Web of Science, Scopus, EMBASE and Cochrane Collaboration were searched for trials assessing the effect of sCPR vs. CCC on resuscitation outcomes after adult OHCA. Random-effects model meta-analysis was applied to calculate the mean deviation (MD), odds ratio (OR) and 95% confidence interval (CI)., Results: Overall, 3 randomized controlled trials and 12 non-randomized trials met the inclusion criteria. Survival to hospital discharge with sCPR was 10.2% compared to 9.3% in the CCC group (OR = 1.04; 95% CI: 0.93-1.16; p = 0.46). Survival to hospital discharge with good neurological outcome measured with the cerebral performance category (CPC 1 or 2) was 6.5% for sCPR vs. 5.8% for CCC (OR = 1.00; 95% CI: 0.84-1.20; p = 0.98). Prehospital return of spontaneous circulation (ROSC) in sCPR and CCC groups was 15.9% and 14.8%, respectively (OR = 1.13; 95% CI: 0.91-1.39; p = 0.26). Survival to hospital admission with ROSC occurred in 29.5% of the sCPR group compared to 28.4% in CCC group (OR = 1.20; 95% CI: 0.89-1.63; p = 0.24)., Conclusions: This systematic review and meta-analysis concluded that there were no significant differences in the resuscitation outcomes between the use of standard cardiopulmonary resuscitation and chest compression only.

Background: The present meta-analysis of clinical and simulation trials aimed to compare video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (V-DACPR) with conventional audio-instructed dispatcher-assisted bystander cardiopulmonary resuscitation (C-DACPR)., Methods: We searched PubMed, Embase, Web of Science, Cochrane Collaboration databases and Scopus from inception until June 10, 2021. The primary outcomes were the prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and survival to hospital discharge with a good neurological outcome for clinical trials, and chest compression quality for simulation trials. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) indicated the pooled effect. The analyses were performed with the RevMan 5.4 and STATA 14 software., Results: Overall, 2 clinical and 8 simulation trials were included in this meta-analysis. In clinical trials, C-DACPR and V-DACPR were characterised by, respectively, 11.8% vs. 24.3% of prehospital ROSC (OR = 0.46; 95% CI: 0.30, 0.69; I 2 = 66%; p  < .001), 10.7% vs. 22.3% of survival to hospital discharge (OR = 0.46; 95% CI: 0.30, 0.70; I  < .001), and 6.3% vs. 16.0% of survival to hospital discharge with a good neurological outcome (OR = 0.39; 95% CI: 0.23, 0.67; 2 = 69%; p  < .001), and 6.3% vs. 16.0% of survival to hospital discharge with a good neurological outcome (OR = 0.39; 95% CI: 0.23, 0.67; I 2 = 73%; p  < .001). In simulation trials, chest compression rate per minute equalled 91.3 ± 22.6 for C-DACPR and 107.8 ± 12.6 for V-DACPR (MD = -13.40; 95% CI: -21.86, -4.95; I 2 = 97%; p  = .002). The respective values for chest compression depth were 38.7 ± 14.3 and 41.8 ± 12.5 mm (MD = -2.67; 95% CI: -8.35, 3.01; I 2 = 98%; p  = .36)., Conclusions: As compared with C-DACPR, V-DACPR significantly increased prehospital ROSC and survival to hospital discharge. Under simulated resuscitation conditions, V-DACPR exhibited a higher rate of adequate chest compressions than C-DACPR.Key messagesBystander cardiopulmonary resuscitation parameters significantly depend on the dispatcher's support and the manner of the support provided.Video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation can increase the rate of prehospital return of spontaneous circulation and survival to hospital discharge.Video-instructed dispatcher-assisted bystander cardiopulmonary resuscitation improves the quality of chest compressions compared with dispatcher-assisted resuscitation without video instruction.

Background/context: Heart failure (HF) is a heterogeneous condition characterized by increased morbidity and mortality., Objective: 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., Materials and Methods: 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., Results: 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)., Conclusions: 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.

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 × 10 5 /ml to 2.8 × 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-μm 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., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Patients with abdominal aortic aneurysm (AAA) have a higher risk of cardiovascular (CV) events, which seems to be associated with disturbed platelet (PLT) function. Endovascular aneurysm repair (EVAR) is an emerging, less-invasive treatment alternative to surgical AAA repair. Both platelet function abnormalities in patients with AAA and the effect of EVAR on platelet function are poorly understood. In this review, we aim to fill the gap regarding the effect of EVAR on PLT function in AAA patients by discussing PLT function disturbances in patients with AAA, PLT function changes after EVAR, evidence from clinical studies regarding PLT function before and after EVAR, and antiplatelet or and antithrombotic treatment in patients undergoing EVAR. The goal of our review is to summarize the contemporary knowledge and initiate further studies to better understand PLT function changes in patients undergoing EVAR, optimize the pharmacotherapy before and after EVAR and further improve outcomes in this group of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Burban, Idzik, Gelo, Filipiak, Jakimowicz, Jama, Grabowski, Gasecka and Siniarski.)

Background: MicroRNAs (miRNA, miR) have an undeniable physiological and pathophysiological significance and act as promising novel biomarkers. The aim of the study was to investigate blood-derived miRNAs and their association with long-term all-cause mortality in patients with multivessel disease (MVD) suffering from acute coronary syndrome (ACS)., Materials and Methods: This study was an observational prospective study, which included 90 patients with MVD and ACS. Expression of miR-125a, miR-125b, and miR-223 was analysed by polymerase chain reaction (PCR). Patients were followed-up for a median of 7.5 years. All-cause mortality was considered as the primary endpoint. Adjusted Cox-regression analysis was performed for prediction of events., Results: Elevated expression of miR-125b (>4.6) at the time-point of ACS was associated with increased long-term all-cause mortality (adjusted [adj.] hazard ratio [HR] = 11.26, 95% confidence interval [95% CI]: 1.15-110.38; p = 0.038). The receiver operating characteristic (ROC) analysis showed a satisfactory c-statistics for miR-125b for the prediction of long-term all-cause mortality (area under the curve [AUC] = 0.76, 95% CI: 0.61-0.91; p = 0.034; the negative predictive value of 98%). Kaplan-Meier time to event analysis confirmed an early separation of the survival curves between patients with high vs low expression of miR-125b ( p = 0.003). An increased expression of miR-125a and miR-223 was found in patients with non-ST-segment elevation ACS (NSTE-ACS) as compared to those with ST-segment elevation myocardial infarction (STEMI) ( p = 0.043 and p = 0.049, respectively) with no difference in the expression of miR-125b between the type of ACS., Conclusion: In this hypothesis generating study, lower values of miR-125b were related to improved long-term survival in patients with ACS and MVD. Larger studies are needed to investigate whether miR-125b can be used as a suitable predictor for long-term all-cause mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gager, Eyileten, Postula, Gasecka, Jarosz-Popek, Gelbenegger, Jilma, Lang and Siller-Matula.)

Objectives: Patients with bicuspid aortic valve (BAV) stenosis were excluded from the pivotal trials of transcatheter aortic valve implantation (TAVI). We compared the in-hospital and long-term outcomes between patients undergoing TAVI for bicuspid and tricuspid aortic valve (TAV) stenosis., Methods: We performed a retrospective registry-based analysis on patients who underwent TAVI for BAV and TAV at five different centers between January 2009 and August 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were in-hospital mortality, procedural complications, and valve performance., Results: Of 1,451 consecutive patients who underwent TAVI, two propensity-matched cohorts consisting of 130 patients with BAV and 390 patients with TAV were analyzed. All-cause mortality was comparable in both groups up to 10 years following TAVI ( HR 1.09, 95% CI : 0.77-1.51). Device success and in-hospital mortality were comparable between the groups (96 vs. 95%, p = 0.554 and 2.3 vs. 2.1%, p = 0.863, respectively). Incidence of procedural complications was similar in both groups, with a trend toward a higher rate of stroke in patients with BAV (5 vs. 2%, p = 0.078). Incidence of moderate or severe paravalvular leak (PVL) at discharge was comparable in both groups (2 vs. 2%, p = 0.846). Among patients with BAV, all-cause mortality was similar in self-expanding and balloon-expandable prostheses ( HR 1.02, 95% CI : 0.52-1.99) and lower in new-generation devices compared to old-generation valves ( HR 0.27, 95% CI 0.12-0.62)., Conclusion: Patients who had undergone TAVI for BAV had comparable mortality to patients with TAV up to 10 years after the procedure. The device success, in-hospital mortality, procedural complications, and PVL rate were comparable between the groups. The high rate of neurological complications (5%) in patients with BAV warrants further investigation., Competing Interests: AW: proctor for Medtronic. ZH: proctor for Medtronic and Abbott. RP: lecture honoraria for Edwards Lifescience. MG: lecture honoraria, proctor and advisory board member of Boston Scientific. DJ: proctor for Edwards Lifesciences. JK: lecture honoraria and proctor for Medtronic, Boston Scientific, Abbott. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gasecka, Walczewski, Witkowski, Dabrowski, Huczek, Wilimski, Ochała, Parma, Scisło, Rymuza, Zbroński, Szwed, Grygier, Olasińska-Wiśniewska, Jagielak, Targoński, Opolski and Kochman.)

Background: Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs)., Objectives: Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT., Methods: We compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry., Results: Patients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively)., Conclusion: Higher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the adult population. Herein, is a systematic review with meta-analysis to determine the impact of AF/atrial flutter (AFL) on mortality, as well as individual complications in patients hospitalized with the coronavirus disease 2019 (COVID-19)., Methods: A systematic search of the SCOPUS, Medline, Web of Science, CINAHL and Cochrane databases was performed. The a priori primary outcome of interest was in-hospital mortality. A random-effects model was used to pool study results., Results: Nineteen studies which included 33,296 patients were involved in this meta-analysis. Inhospital mortality for AF/AFL vs. no-AF/AFL groups varied and amounted to 32.8% vs. 14.2%, respectively (risk ratio [RR]: 2.18; 95% confidence interval [CI]: 1.79-2.65; p < 0.001). In-hospital mortality in new onset AF/AFL compared to no-AFAFL was 22.0% vs. 18.8% (RR: 1.86; 95% CI: 1.54-2.24; p < 0.001). Intensive care unit (ICU) admission was required for 17.7% of patients with AF/AFL compared to 10.8% for patients without AF/AFL (RR: 1.94; 95% CI: 1.04-3.62; p = 0.04)., Conclusions: The present study reveals that AF/AFL is associated with increased in-hospital mortality and worse outcomes in patients with COVID-19 and may be used as a negative prognostic factor in these patients. Patients with AF/AFL are at higher risk of hospitalization in ICU. The presence of AF/AFL in individuals with COVID-19 is associated with higher risk of complications, such as bleeding, acute kidney injury and heart failure. AF/AFL may be associated with unfavorable outcomes due to the hemodynamic compromise of cardiac function itself or hyperinflammatory state typical of these conditions.

Background: 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., Methods: 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., Results: 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; p < 0.001), in good vs. poor outcome 12.0 ± 3.6 vs. 29.4 ± 14.5 (MD: -8.13; 95% CI: -8.37 to -7.88; p < 0.001) 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; p < 0.001)., Conclusions: 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; I2 = 74%; p = 0.20), the rarer intensive care unit admission (6.4% vs. 23.4%; OR = 0.19; 95% CI: 0.06-0.54; I2 = 77%; p = 0.002) as well as rarer mechanical ventilation (6.5% vs. 18.9%; OR = 0.36; 95% CI: 0.16-0.80; I2 = 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.

Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.

Introduction: Preliminary retrospective reports showed that zinc supplementation may decrease mortality in patients with COVID-19, postulating the potential therapeutic efficacy of zinc in the management of the disease., Objectives: We sought to summarize the studies published to date regarding the antiviral activity of zinc in patients with COVID-19., Patients and Methods: A meta-analysis was performed to compare the outcomes of hospitalized patients receiving zinc supplementation and those treated with standard care. The primary outcome was survival to hospital discharge. Secondary outcomes were in-hospital mortality and length of stay in hospital or intensive care unit (ICU)., Results: Data relating to 1474 patients included in 4 studies were analyzed. Survival to hospital discharge was 56.8% in the zinc group compared with 75.9% in the nonzinc group (P = 0.88). In-hospital mortality was 22.3% in the zinc group compared with 13.6% in the standard care group (P = 0.16). The mean (SD) length of hospital stay was 7.7 (3.7) days in the zinc group and 7.2 (3.9) days in the standard treatment group (P <⁠0.001). The mean (SD) length of ICU stay was 4.9 (1.7) days in the zinc group and 5.8 (1.9) days in the standard care group (P = 0.009)., Conclusions: Zinc supplementation did not have any beneficial impact on the course of COVID-19 evaluated as survival to hospital discharge and in-hospital mortality. The zinc-supplemented group had longer hospital stay despite shorter ICU stay. At present, there are no evidence-based data to support routine zinc supplementation in patients with COVID-19.

Background: The main purposes of this meta-analysis are to update the information about the impact of coronavirus disease 2019 (COVID-19) pandemic on outcomes of in-hospital cardiac arrest (IHCA) and to investigate the impact of being infected by by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) on IHCA outcomes., Methods: The current meta-analysis is an update and follows the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)., Results: In analyses, pre- and intra-COVID-19 periods were observed for: shockable rhythms in 17.6% vs. 16.2% (odds ratio [OR]: 1.11; 95% confidence interval [CI]: 0.71-1.72; p = 0.65), return of spontaneous circulation (ROSC) in 47.4% vs. 44.0% (OR: 1.36; 95% CI: 0.90-2.07; p = 0.15), 30-day mortality in 59.8% vs. 60.9% (OR: 0.95; 95% CI: 0.75-1.22; p = 0.69) and overall mortality 75.8% vs. 74.7% (OR: 0.80; 95% CI: 0.49-1.28; p = 0.35), respectively. In analyses, SARS-CoV-2 positive and negative patients were observed for: shockable rhythms in 9.6% vs. 19.8% (OR: 0.51; 95% CI: 0.35-0.73; p < 0.001), ROSC in 33.9% vs. 52.1% (OR: 0.47; 95% CI: 0.30-0.73; p < 0.001), 30-day mortality in 77.2% vs. 59.7% (OR: 2.08; 95% CI: 1.28-3.38; p = 0.003) and overall mortality in 94.9% vs. 76.7% (OR: 3.20; 95% CI: 0.98-10.49; p = 0.05), respectively., Conclusions: Despite ROSC, 30-day and overall mortality rate were not statistically different in pre- vs. intra-COVID-19 periods, a lower incidence of ROSC and higher 20-day mortality rate were observed in SARS-CoV-2 (+) compared to SARS-CoV-2 (-) patients.