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Background: To evaluate incidence and search for possible predictors of brain fog and quality of life at work (QoL-W) among low-to-moderate risk subjects previously hospitalized due to COVID-19., Material and Methods: Participants aged ≥18 retrospectively reported 8 brain fog symptoms pre-COVID-19, at 0-4, 4-12 and >12 weeks post-infection via validated clinical questionnaire. The QoL-W was assessed with a 4-point Likert scale where 0, 1, 2, and 3 meant no, mild, moderate, and severe impairment in performing activities at work, respectively. Data on age, sex, comorbidities, and laboratory results (including first in-hospital high-sensitivity cardiac troponin I [hs-cTnI] measurement) were gathered., Results: The study included 181 hospitalized subjects (age Me = 57 years), 37.02% women. Most had low disease severity ( Modified Early Warning Score = 1, 77.90%) and low comorbidity (Charlson Comorbidity Index 0: 28.72%, 1-2: 34.09%), with no intensive care unit treatment needed. COVID-19 led to almost 3-fold increased brain fog symptoms, with incidence of 58.56%, 53.59%, and 49.17% within 4, 4-12, and >12 weeks, respectively (p < 0.001). First in-hospital hs-cTnI levels were 47.3% higher in participants who later presented with brain fog at median follow-up of 26.7 weeks since the diagnosis of the SARS-CoV-2 infection. Individuals who experienced at least one brain fog symptom at follow-up, had elevated hs-cTnI, less often presented with atrial fibrillation, and used anticoagulants during initial hospitalization due to COVID-19. The Hs-cTnI >11.90 ng/l predicted brain fog symptoms in multivariable model. COVID-19 was associated with 3.6‑fold, 3.0‑fold, and 2.4-fold QoL-W deterioration within 4, 4-12, and >12 weeks post-infection (p < 0.05). Subjects with QoL-W decline >12 weeks were younger, mostly women, had more brain fog symptoms, and higher platelet counts. Multivariable models with self-reported brain fog symptoms (responding coherently and recalling recent information), age, and sex exhibited good discriminatory power for QoL-W impairment (area under the receiver operating characteristic curve 0.846, 95% CI: 0.780-0.912)., Conclusions: This study highlighted that in non-high-risk subjects hospitalized during the first 2 pandemic's waves: 1) brain fog was common, affecting nearly half of individuals, and impacting QoL-W >12 weeks after initial infection, 2) after 3 months of COVID-19 onset, the decline in QoL-W was primarily attributed to brain fog symptoms rather than demographic factors, health conditions, admission status, and laboratory findings, 3) components of brain fog, such as answering in an understandable way or recalling new information increased the likelihood of significantly lower QoL-W up to tenfold, 4) biochemical indicators, such as the first hs-cTnI level, might predict the risk of experiencing brain fog symptoms and indirectly decreased QoL-W >12 weeks after COVID-19 onset. Occupational medicine practitioners should pay particular attention to younger and female subjects after COVID-19 complaining of problems with answering questions in understandable way or recalling new information as they have an increased risk of QoL-W impairment. Med Pr Work Health Saf. 2024;75(1):3-17., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

An increased risk of atherosclerotic and thrombotic complications characterizes connective tissue diseases. Endothelial dysfunction is the basis for the initiation and progression of atherosclerosis and thrombosis. We present systemic lupus erythematosus (SLE) as a model rheumatic disease with endothelial dysfunction and discuss its mechanisms, factors that influence the early onset and rapid progression of atherosclerosis, and the increased risk of thromboembolic events. We focus on established methods to improve endothelium function, including statins, antiplatelet, and antithrombotic therapy. Hypercoagulable and hypofibrinolitic states and a hyperinflammatory response characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Several pathogenic mechanisms are typical for an acute phase of Covid-19 post-Covid syndrome and connective tissue diseases: endothelial dysfunction, elevated antiphospholipid antibody titer, activation of the complement system, and formation of extracellular neutrophil traps (NET). The current review discusses the mechanisms underlying SLE and the COVID-19 in the context of endothelial function, atherosclerosis, and thrombosis (Graphical abstract). Key Points • The pathophysiology of systemic lupus erythematosus (SLE) and Covid-19 shows some similarities, such as endothelial cell activation and dysfunction, the activation of complementary systems, the presence of antiphospholipid antibodies, and the formation of extracellular neutrophil traps. • Autoimmunity in both diseases creates the basis for hyperinflammatory, hypercoagulable, and hypofibrinolitic states and their thromboembolic complications. • This paper presents our perspective on the mechanisms behind the cardiovascular manifestations of SLE and COVID-19, with a particular emphasis on endothelial dysfunction. Covid-19 and systemic lupus erythematosus-potential similarities in pathophysiology. Figures of the panel illustrate the clinical manifestations of endothelial dysfunction, atherosclerosis, and thromboembolism, including coronary artery disease ([A] coronary angiography with left anterior descending artery stenosis and [B] scintigraphy with reduced perfusion in the myocardial apical segments), stroke ([C] carotid angiography, left carotid artery occlusion) and pulmonary embolism ([D]computed tomography with thrombus in the right pulmonary artery)., (© 2023. International League of Associations for Rheumatology (ILAR).)

Background: Limited evidence exists on sex differences in post-COVID fatigue among non-hospitalized patients. Therefore, aim of the study was to evaluate the course of chronic fatigue symptoms in non-hospitalized subjects with the SARS-CoV-2 infection, according to sex., Methods: Patients and staff from the University Hospital in Krakow anonymously and retrospectively completed neuropsychological questionnaire that included eight symptoms of chronic fatigue syndrome. The presence of these symptoms was assessed before COVID-19 and 0-4, 4-12, and >12 weeks postinfection. The inclusion criteria were as follows: age 18 or more years, >12 weeks since the onset of the SARS-CoV-2 infection, and diagnosis confirmed by the RT-PCR from anasopharyngeal swab., Results: We included 303 patients (79.53% women, 47.52% medical personnel) assessed retrospectively after a median of 30 (interquartile range: 23-35) weeks since the onset of symptoms. A higher prevalence of at least one chronic fatigue symptom was found in females in all time intervals after the onset of COVID-19 compared to males (p < .036). Women, compared to men, more often experienced persistent fatigue, not caused by effort and persisting after rest (for <4 weeks, odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.13-4.73; for 4-12 weeks, OR = 1.95, 95% CI: 1.06-3.61), non-restorative sleep (for <4 weeks, OR = 2.17, 95% CI: 1.23-3.81; for >12 weeks, OR = 1.95, 95% CI: 1.03-3.71), and sore throat (for <4 weeks, OR = 1.97, 95% CI: 1.03-3.78; for 4-12 weeks, OR = 2.76, 95% CI: 1.05-7.27). Sex differences in headache, arthralgia, and prolonged postexercise fatigue were observed only during the first 4 weeks (OR = 2.59, 95% CI: 1.45-4.60, OR = 2.97, 95% CI: 1.02-8.64, and OR = 1.87, 95% CI: 1.01-3.51, respectively). There were no differences between women and men in myalgia and self-reported lymph node enlargement., Conclusions: The course of post-COVID fatigue differs significantly between sexes in non-hospitalized individuals with COVID-19, with women more often suffering from persistent fatigue, not caused by effort and persisting after rest, non-restorative sleep, and sore throat., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Discrepancies exist regarding the clinical course and prognostic factors for post-COVID fatigue. Therefore, our aim was to assess the timely course of fatigue and its possible predictors in patients previously hospitalised due to SARS-CoV-2 infection., Material and Methods: Patients and employees of the University Hospital in Krakow were assessed with the use of a validated neuropsychological questionnaire. Included were participants aged 18 or more, previously hospitalised due to COVID-19, who completed questionnaires only once > 3 months after the onset of infection. Individuals were retrospectively asked about the presence of eight symptoms of chronic fatigue syndrome at four timepoints: before COVID-19, within 0-4 weeks, 4-12 weeks, and > 12 weeks post-infection., Results: We enrolled 204 patients [40.2% women, median age 58 (46-66) years] evaluated after a median of 187 (156-220) days from the first positive nasal swab test for SARS-CoV-2. The most common comorbidities were hypertension (44.61%), obesity (36.27%), smoking (28.43%), and hypercholesterolemia (21.08%); none of the patients required mechanical ventilation during hospitalisation. Before COVID-19, 43.62% of patients reported at least one symptom of chronic fatigue. Within 4, 4-12, and > 12 weeks after COVID-19, the prevalence of chronic fatigue was 76.96%, 75.49%, and 66.17%, respectively (all p < 0.001). The frequency of chronic fatigue symptoms decreased within > 12 weeks following the onset of infection but did not return to baseline values, except for self-reported lymph node enlargement. In a multivariable linear regression model, the number of fatigue symptoms was predicted by female sex [β 0.25 (0.12; 0.39), p < 0.001 and 0.26 (0.13; 0.39), p < 0.001 for weeks 0-12 and > 12, respectively], and age [for < 4 weeks, β -0.12 (-0.28; -0.01), p = 0.029]., Conclusions: Most patients previously hospitalised due to COVID-19 suffer from fatigue > 12 weeks after infection onset. The presence of fatigue is predicted by female sex and - only for the acute phase - age.

Introduction: Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex., Material and Methods: We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0-4, 4-12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab., Results: The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161-248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38-6.72; 4-12 weeks, OR 2.51, 95% CI: 1.02-6.14; > 12 weeks, OR 3.74, 95% CI: 1.12-12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41-4.54; 4-12 weeks, OR 3.74, 95% CI: 1.93-7.24; > 12 weeks, OR 2.00, 95% CI: 1.01-3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36-5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44-4.48 and OR 2.43, 95% CI: 1.37-4.31 for < 4 and 4-12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted., Conclusions: Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog.

Background: The use of doxorubicin is associated with an increased risk of acute and long-term cardiomyopathy. Despite the constantly growing number of cancer survivors, little is known about the transcriptional mechanisms which progress in the time leading to a severe cardiac outcome. It is also unclear whether long-term transcriptomic alterations related to doxorubicin use are similar to transcriptomic patterns present in patients suffering from other cardiomyopathies., Methods: We have sequenced miRNA from total plasma and extracellular vesicles (EVs) from 66 acute lymphoblastic leukemia (ALL) survivors and 61 healthy controls (254 samples in total). We then analyzed processes regulated by differentially expressed circulating miRNAs and cross-validated results with the data of patients with clinically manifested cardiomyopathies., Results: We found that especially miRNAs contained within EVs may be informative in terms of cardiomyopathy development and may regulate pathways related to neurotrophin signaling, transforming growth factor beta (TGFβ) or epidermal growth factor receptors (ErbB). We identified vesicular miR-144-3p and miR-423-3p as the most variable between groups and significantly correlated with echocardiographic parameters and, respectively, for plasma: let-7g-5p and miR-16-2-3p. Moreover, vesicular miR-144-3p correlates with the highest number of echocardiographic parameters and is differentially expressed in the circulation of patients with dilated cardiomyopathy. We also found that distribution of particular miRNAs between of plasma and EVs (proportion between compartments) e.g., miR-184 in ALL, is altered, suggesting changes within secretory and miRNA sorting mechanisms., Conclusions: Our results show that transcriptomic changes resulting from doxorubicin induced myocardial injury are reflected in circulating miRNA levels and precede development of the late onset cardiomyopathy phenotype. Among miRNAs related to cardiac function, we found vesicular miR-144-3p and miR-423-3p, as well as let-7g-5p and miR-16-2-3p contained in the total plasma. Selection of source for such studies (plasma or EVs) is of critical importance, as distribution of some miRNA between plasma and EVs is altered in ALL survivors, in comparison to healthy people, which suggests that doxorubicin-induced changes include miRNA sorting and export to extracellular space., (© 2022. The Author(s).)

The number of patients with coronary artery disease and ischaemic heart failure - and those with terminal heart failure - is increasing despite improvements in medical and interventional therapies of ischaemic heart disease - and, over the next decades, it is projected to continue to increase further. Observer-independent, reproducible imaging techniques play a fundamental role in objective evaluation of both conventional (such as surgical or percutaneous) myocardial revascularization and novel therapeutic approaches to reduce myocardial ischaemia, improve contractility and prevent adverse myocardial remodelling. To be applicable to clinical practice, the clinical study design and data should best be rooted in everyday clinical practice. Accurate and reproducible assessment of left ventricular ejection fraction, left ventricular volumes, myocardial perfusion and function is one of the most important objectives of cardiac imaging. Current techniques used both in clinical studies and in everyday clinical practice include 2- and 3-dimensional echocardiography, magnetic resonance imaging, single-photon emission computed tomography and positron emission tomography; each of these has its strengths and limitations. We review present evidence on the role of single-photon emission computed tomography as a technique that may offer, through being observer-independent, the most objective evaluation of evolution of left ventricular perfusion, volumes and ejection fraction., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia Sp. z o. o.)

Introduction: Clinical trial applicability to routine clinical practice is a fundamental consideration. Little is known about factors that determine enrolment (vs. non-enrolment) in chronic ischaemic heart failure (CIHF) interventional randomized controlled trials (iRCT)., Aim: To compare clinical characteristics and medical therapy in eligible-and-enrolled (E-E) vs. eligible-but-not-enrolled (E-NE) patients in CIHF myocardial regeneration iRCTs., Material and Methods: Clinical characteristics and medical treatment were compared for E-E and E-NE in 4 periods (32 months): P1 (iRCT#1 recruitment), P2 (between iRCT#1 and iRCT#2), P3 (iRCT#2 recruitment), P4 (post iRCT#2). iRCT#1 and iRCT#2 shared inclusion/exclusion criteria., Results: Evaluation involved 5,436 hospitalized patients (P1-P4; CIHF-526). 283 were iRCT eligible (53.8%). The eligibility rate was similar throughout P1-P4 (43.1-58.5%, p = 0.08). Eligible patient characteristics and pharmacotherapy did not differ in recruitment vs. non-recruitment periods. Principal reasons for ineligibility were recent/planned cardiac intervention outside iRCT (22.8%), age above threshold (14.6%) and coexisting disease as the exclusion criterion (12.2%). Primary reasons for eligible patient non-enrolment ( n = 89) were other trial participation (52.8%) and no consent (28.1%). E-E patients did not differ from E-NE in characteristics including CIHF medical management and clinical stage; the exception was more severe left ventricular impairment in E-E (LVEF 31.2 vs. 33.9%, p = 0.039; end-diastolic volume 197.8 vs. 160.4 ml, p < 0.0001)., Conclusions: CIHF medical management was similar in E-E and E-NE. Ineligibility resulted mainly from recent/planned intervention outside iRCT and age > 80 years. LV impairment was more severe in E-E patients, consistent with higher-risk patient enrolment in CIHF-iRCTs. This contrasts with typical lower-risk patient enrolment in other cardiovascular RCT types and populations., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Competing Interests: The authors declare no conflict of interest.

Introduction: CIRCULATE-AMI (NCT03404063), a cardiac magnetic resonance imaging (cMRI) infarct size-reduction-powered double-blind randomized controlled trial (RCT) of standardized Wharton jelly multipotent stem cells (WJMSCs, CardioCell Investigational Medical Product) vs. placebo (2 : 1) transcoronary transfer on acute myocardial infarction (AMI) day ~5-7, is preceded by safety and feasibility evaluation in a pilot study cohort (CIRCULATE-AMI PSC)., Aim: To evaluate WJMSC transplantation safety and evolution of left ventricular (LV) remodeling in CIRCULATE-AMI PSC., Material and Methods: In 10 consecutive patients (32-65 years, peak CK-MB 533 ±89 U/l, cMRI-LVEF 40.3 ±2.7%, cMRI-infarct size 20.1 ±2.8%), 30 × 10 6 WJMSCs were administered using a novel cell delivery-dedicated, coronary-non-occlusive method (CIRCULATE catheter). Other treatment was guideline-based., Results: WJMSC transfer was safe and occurred in the absence of coronary (TIMI-3 in all) or myocardial (corrected TIMI frame count (cTFC) 45 ±8 vs. 44 ±9, p = 0.51) flow deterioration or troponin elevation. By 3 years, 1 patient died from a new, non-index territory AMI; there were no other major adverse cardiovascular and cerebrovascular events (MACCE) and no adverse events that might be related to WJMSCs. cMRI infarct size was reduced from 33.2 ±7.6 g to 25.5 ±6.4 g at 1 year and 23.1 ±5.6 g at 3 years ( p = 0.03 vs. baseline). cMRI, SPECT, and echo showed a consistent, statistically significant increase in LVEF at 6-12 months (41.9 ±2.6% vs. 51.0 ±3.3%, 36.0 ±3.9% vs. 44.9 ±5.0%, and 38.4 ±2.5% vs. 48.0 ±2.1% respectively, p < 0.01 for all); the effect was sustained at 3 years., Conclusions: CIRCULATE-AMI PSC data suggest that WJMSC transcoronary application ~5-7 days after large AMI in humans is feasible and safe and it may be associated with a durable LVEF improvement. CIRCULATE-AMI RCT will quantify the magnitude of LV adverse remodeling attenuation with CardioCell/placebo administration., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Background: Olfactory dysfunction evaluated with time-consuming tests was more common in patients with multiple sclerosis (MS) than in controls and correlated with neurological deficit. The aim of the present study was to compare olfactory function between patients with relapsing-remitting MS (RRMS) and controls with short and simple screening tool-the Sniffin' Sticks Identification Test (SSIT)-and search for its association with clinical and radiological features of the disease., Methods: The study included 30 controls and 30 patients with RRMS treated with disease-modifying therapies-injectables (interferon β or glatiramer acetate, N = 18) and oral drugs (dimethyl fumarate or fingolimod, N = 12). Hyposmia was defined as a score of 6 points or fewer in the SSIT olfactory test. The data concerning number of previous relapses, disability in Expanded Disability Status Scale (EDSS), and recent brain magnetic resonance imaging (MRI) scan were collected. Moreover, thalamic volume and third ventricle width were recorded in every patient. Additionally, cognition and fatigue in patients were evaluated 24 months after olfactory assessment with the Symbol Digit Modalities Test (SDMT) and Fatigue Scale for Motor and Cognitive Functions (FSMC), respectively., Results: Patients with RRMS had a higher risk of hyposmia than controls (66.7% vs 36.7%, OR = 1.82, 95% CI, 1.10-3.67, P = .02). Neither inflammatory (number of previous relapses or new brain MRI lesions) nor neurodegenerative (EDSS, SDMT, and FSMC scores; thalamic volume; third ventricle width) MS features did not correlate with SSIT score ( P > .05). In patients treated with oral drugs, olfactory dysfunction correlated with FSMC cognitive subscale ( r = -0.90, P = .006)., Conclusions: Olfactory dysfunction is nearly twice as common in RRMS as in controls and correlates with fatigue level in patients treated with dimethyl fumarate or fingolimod.

Introduction: Recent analysis from CHART-1 study indicated that the therapeutic effects of trans-endocardial cardiopoetic cell transplantation in chronic ischemic heart failure (iCHF) may be lost with an increasing number of injections perfomed to deliver therapeutic cells., Aim: To evaluate global and regional contractility and diastolic function of the left ventricle of patients with iCHF who received trans-endomyocardial cardiopoietic stem cells (CSCs) delivery or sham procedures., Material and Methods: The study included patients (mean age: 60.8 ±7.1 years) with iCHF (left ventricular ejection fraction (LVEF) < 35%) and a history of hospitalization for worsening heart failure within 12 months despite optimal medical therapy. The patients underwent transmyocardial CSCs transplantation using perforated needle technique or a sham procedure. The wall motion score index (WMSI), LVEF, transmitral E-velocity, E-wave deceleration time, E/A-ratio, and E/e'-mean value were measured with two-dimensional echocardiography on days 1 and 30., Results: A total of 170 segments were analyzed, including 48 targeted segments where 92 injections of 0.5 ml of CSCs were performed. In the transendocardial injections cohort, a decrease in regional contractility was observed in 30.6% (26/85) and 18.9% (16/85) of the segments on days 1 and 30, respectively. This was accompanied by an increase in WMSI by 0.32 ±0.06 and 0.19 ±0.18 (day 1, p = 0.02, day 30, p = 0.03) and a reduction in LVEF (-3.15 ±1.23%, p = 0.065)., Conclusions: Transendocardial injections performed to deliver therapeutic cells were associated with myocardial injury. This adverse effect remained, albeit at a lesser degree, at 30-days. Mechanical injury with trans-endocardial delivery of progenitor cells using the "needle technique" may counterbalance, at least in part, any cell-related benefit(s)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Background: There is still a need for studies on the quality of life (QoL) at work among COVID-19 survivors. Therefore, we aimed to evaluate the association between the brain fog symptoms and the QoL at work in non-hospitalized patients with previous SARS-CoV-2 infection. Methods: Three hundred non-hospitalized patients (79.33% women; median age, 36 years; interquartile range, 30-48 years) were included in the final analysis. An anonymous neuropsychological questionnaire containing eight different questions on the presence of brain fog symptoms in four time intervals, i.e., pre-COVID-19 and 0-4, 4-12, and >12 weeks after infection, was retrospectively introduced to patients and staff of the University Hospital in Krakow. Additionally, a four-point Likert scale was used to evaluate QoL at work in four time periods. Included were participants aged ≥ 18 years in whom the diagnosis of COVID-19 was confirmed by the RT-PCR from nasopharyngeal swab and the first symptoms occurred no earlier than 3 months before the completion of the questionnaire. Results: Before SARS-CoV-2 infection, 28.00% ( n = 84) of patients reported poor QoL at work. Within 4, 4-12, and >12 weeks after infection, a decrease in QoL was observed in 75.67% ( n = 227), 65.00% ( n = 195), and 53.66% ( n = 161) of patients, respectively ( p < 0.001). With increasing deterioration of the QoL at work, the number of brain fog symptoms increased, and patients with severe QoL impairment exhibited a median of five symptoms for <4, 4-12, and >12 weeks post-COVID-19. In the multivariable logistic regression model, predictors of the deterioration of the QoL at work depended on the time from COVID-19 onset; in the acute phase of the disease (<4 weeks), it was predicted by impairment in remembering information from the past (OR 1.88, 95%CI: 1.18-3.00, p = 0.008) and multitasking (OR 1.96, 95%CI: 1.48-2.58, p < 0.001). Furthermore, an impairment in the QoL at work 4-12 weeks and >12 weeks after COVID-19 was independently associated with age (OR 0.46, 95%CI: 0.25-0.85, p = 0.014 and OR 1.03, 95%CI: 1.01-1.05, p = 0.025, respectively), problems with multitasking (OR 2.05, 95%CI: 1.40-3.01, p < 0.001 and OR 1.75, 95%CI: 1.15-2.66, p = 0.009, respectively), answering questions in an understandable/unambiguous manner (OR 1.99, 95%CI: 1.27-3.14, p = 0.003 and OR 2.00, 95%CI: 1.47-2.36, p = 0.001, respectively), and, only for the >12 week interval, problems with remembering information from the past (OR 2.21, 95%CI: 1.24-3.92, p = 0.007). Conclusions: Certain brain fog symptoms, such as impaired memory or multitasking, are predictors of a poorer QoL at work not only during the acute phase of COVID-19 but also within more than 12 weeks after the onset of infection.

We aimed to search whether neurological symptoms or signs (NSS) and the MEWS (Modified Early Warning Score) score were associated with in-hospital mortality or oxygen requirement during the first 14 days of hospitalization in COVID-19 patients recruited at the University Hospital in Krakow, Poland. The detailed clinical questionnaires on twenty NSS were either filled out by patients prospectively or retrospectively assessed by neurologists based on daily medical records. NSS were considered high or low-risk if they were associated with increased or decreased mortality in the univariable analysis. This cohort study included 349 patients with COVID-19 (median age 64, interquartile range (51-77), women 54.72%). The presence of high-risk NSS (decreased level of consciousness, delirium, seizures, and symptoms of stroke or transient ischemic attack) or its combination with the absence of low-risk NSS (headache, dizziness, decreased mood, and fatigue) increased the risk of in-hospital mortality in SARS-CoV-2 infection 3.13 and 7.67-fold, respectively. The presence of low-risk NSS decreased the risk of in-hospital mortality in COVID-19 patients more than 6-fold. Death in patients with SARS-CoV-2 infection, apart from NSS, was predicted by older age, neoplasm, and higher MEWS scores on admission. High-risk NSS or their combination with the absence of low-risk NSS increased the risk of oxygen requirement during hospitalization in COVID-19 patients 4.48 and 1.86-fold, respectively. Independent predictors of oxygen therapy during hospitalization in patients with SARS-CoV-2 infection were also older age, male sex, neoplasm, and higher MEWS score on admission.

Aim of the Study: To assess the influence of age on long-term functional outcome in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT)., Material and Methods: We performed retrospective analysis of 362 AIS patients treated with IVT or IVT and subsequent mechanical thrombectomy in the University Hospital in Krakow, Poland. Patients were categorised into four subgroups by age: (I) below the age of 60, (II) 60 to 69, (III) 70 to 79, and (IV) 80 or more. The outcomes were assessed with modified Rankin scale (mRS) 90 days after stroke onset, and defined as favourable (mRS 0-2), poor (mRS 3-5), or death (mRS = 6)., Results: Patients aged 80 or more compared to those below 60 were more often women (72.64% vs. 26.76%, < 0.001), more often suffered from hypertension (94.34% vs. 60.56%, p < 0.001), ischaemic heart disease (27.36% vs. 8.45%, p = 0.002), atrial fibrillation (49.06% vs. 5.63%, p < 0.001), and premorbid disability (pre-stroke mRS ≥ 1: 17.92% vs. 1.41%, p < 0.001), less often were active smokers (0% vs. 27.14%, p < 0.001), more often had cardioembolic aetiology (50.00% vs. 16.90%, p < 0.001), and less often other stroke aetiology (1.89% vs. 15.49%, < 0.008), had shorter time from stroke onset to IVT (125 [93-180] vs. 140 [110-186] min, p < 0.008), less often underwent mechanical thrombectomy (18.87% vs. 46.48%, p < 0.001), had higher CRP levels (10.3 [3.2-39.8] vs. 4.3 [2.1-9.6] mg/L, p = 0.003), higher maximal systolic blood pressure within 24 hours after IVT (153 [140-170] vs. 138 [120-145] mmHg, p < 0.001), and higher creatinine concentration (88 [68-108] vs. 77 [67-87] μmol/l, p = 0.004), less often had a favourable outcome (48.04% vs. 85.51%, odds ratio [OR] 0.16, 95%CI: 0.07-0.34, p < 0.001), and had a greater risk of death (26.47% vs. 5.80%, OR 5.85, 95%CI: 1.95-17.59, p < 0.001) within three months of stroke onset. Multivariable logistic regression analysis showed that the independent predictors of worse outcome in patients aged 80 or more were NIHSS score after IVT (OR 0.64, 95%CI: 0.53-0.78, p < 0.001), pre-stroke mRS score ≥ 1 (OR 0.10, 95%CI: 0.02-0.61, p = 0.012), and CRP levels (OR 0.96, 95%CI: 0.93-0.99, p = 0.007)., Conclusions: AIS patients treated with reperfusion therapy and aged 80 or more have around a six times higher risk of an unfavourable outcome or death within three months of stroke onset compared to those aged below 60. Higher NIHSS score after IVT, any signs of disability before stroke as measured with mRS, and higher CRP levels are independent risk factors for worse prognosis in the elderly.

Introduction: Systemic lupus erythematosus (SLE) is characterized by early atherothrombosis. Pulse wave velocity (PWV) is a promising tool for the diagnosis of early vascular remodelling and initial atherosclerotic plaque formation. Our objective was to evaluate PWV and its relationship with coronary atherosclerosis and thrombotic biomarkers in patients with SLE., Material and Methods: In 26 patients with SLE with stable clinical conditions, mean age of 39.1 ±11.7 years and without a history of coronary artery disease, multidetector computed tomography (MDCT)-based coronary calcium scoring (CACS) was performed and PWV measured.Laboratory evaluation included serum levels of anticardiolipin and anti-β2-glycoprotein antibodies (anti-β2-GPI), lupus anticoagulant (LA), D-dimers, thrombin-antithrombin complexes (TAT), and von Willebrand factor (vWF)., Results: Multidetector computed tomography revealed coronary calcifications in 8 (30.8%) patients and the median CACS was 52.4 HU (range 2-843.2). The mean PWV was 9.0 ±3.2 m/s and was higher in patients aged > 50 years (+33.7% vs. < 50 years), those with positive LA (+28.2% vs. LA negative), TAT ≥ 10 μg/l (+18.1% vs. < 10 μg/l), vWF ≥ 200 IU/dl (+51.8% vs. < 200 IU/dl) and with coronary atherosclerosis (CACS > 0; +21.4% vs. CACS = 0).In contrast, the duration of the disease, D-dimers, anticardiolipin, and anti-β2-GPI antibodies did not influence PWV. In the group without atherosclerosis (CACS = 0, n =18), patients with vWF ≥ 200 IU/dl had a 19.3% higher PWV compared to the rest., Conclusions: In patients with SLE, PWV was associated with the presence of coronary atherosclerotic lesions in MDCT. Furthermore, arterial stiffness was higher in patients with markers of endothelial dysfunction and a prothrombotic state, suggesting their contribution to the early stages of arterial remodelling in SLE., Competing Interests: The authors declare no conflicts of interest. This study was supported by the grant N40201231/0460 from the Polish Ministry of Science and Higher Education., (Copyright: © 2022 Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji w Warszawie.)

Background: Only a few studies evaluated the role of fasting glucose levels after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Importantly, formal analysis concerning the prognostic role of fasting glucose levels in these patients with and without diabetes mellitus (DM) was not performed. Therefore, we assessed whether fasting normoglycemia (FNG) next morning after AIS treated with IVT was associated with 90-day functional outcome in diabetic and non-diabetic patients., Methods: We retrospectively analyzed 362 AIS patients treated with IVT at The University Hospital in Krakow. FNG was defined as glucose below 5.5 mmol/L. A favorable outcome was defined as modified Rankin score (mRS) of 0-2 at day 90 after AIS onset., Results: At 3-month follow-up, FNG was associated with favorable outcome (87.5% vs. 60.8%, p < 0.001) and decreased risk of death (3.1% vs. 18.1%, p = 0.002). Independent predictors of a favorable outcome for the whole group were: younger age (HR 0.92, 95%CI 0.89-0.95), lower NIHSS score after IVT (HR 0.70, 95%CI 0.65-0.76), lower maximal systolic blood pressure within 24 h after IVT (HR 0.92, 95%CI 0.89-0.95) and FNG (HR 4.12, 95%CI 1.38-12.35). Association between FNG and mortality was found in univariable (HR 1.47, 95%CI 0.04-0.62) but not in multivariable analysis (HR 0.23, 95%CI 0.03-1.81). In subgroup analyses, FNG was an independent predictor of favorable outcome (HR 5.96, 95%CI 1.42-25.1) only in patients without DM., Conclusions: FNG next morning after IVT is an independent protective factor for a favorable long-term outcome in non-diabetic AIS patients.

Background: Previous studies on inflammatory biomarkers in acute ischemic stroke (AIS) produced divergent results. We evaluated whether C-reactive protein (CRP) and white blood cell count (WBC) measured fasting 12-24 h after intravenous thrombolysis (IVT) were associated with outcome in AIS patients without concomitant infection. Methods: The study included 352 AIS patients treated with IVT. Excluded were patients with community-acquired or nosocomial infection. Outcome was measured on discharge and 90 days after stroke onset with the modified Rankin scale (mRS) and defined as poor outcome (mRS 3-6) or death (mRS = 6). Results: Final analysis included 158 patients (median age 72 years (interquartile range 63-82), 53.2% ( n = 84) women). Poor outcome on discharge and at day 90 was 3.8-fold and 5.8-fold higher for patients with CRP ≥ 8.65 mg/L (fifth quintile of CRP), respectively, compared with first quintile (<1.71 mg/L). These results remained significant after adjustment for potential confounders (odds ratio (OR) on discharge = 10.68, 95% CI: 2.54-44.83, OR at day 90 after stroke = 7.21, 95% CI: 1.44-36.00). In-hospital death was 6.3-fold higher for patients with fifth quintile of CRP as compared with first quintile and remained independent from other variables (OR = 4.79, 95% CI: 1.29-17.88). Independent predictors of 90-day mortality were WBC < 6.4 × 10 9 /L (OR = 5.00, 95% CI: 1.49-16.78), baseline National Institute of Health Stroke Scale (NIHSS) score (OR = 1.13 per point, 95% CI: 1.01-1.25) and bleeding brain complications (OR = 5.53, 95% CI: 1.59-19.25) but not CRP ≥ 8.65 mg/L. Conclusions: Non-infective CRP levels are an independent risk factor for poor short- and long-term outcomes and in-hospital mortality in AIS patients treated with IVT. Decreased WBC but not CRP is a predictor for 90-day mortality.

It is known that atrial fibrillation (AF) is associated with the procoagulant state. Several studies have reported an increase of circulating microparticles in AF, which may be linked to a hypercoagulable state, atrial thrombosis and thromboembolism. We evaluated in our study alterations in both platelet (PMP, CD42b) and endothelial-derived (EMP, CD144) microparticle levels on anticoagulant therapy with rivaroxaban in nonvalvular AF. After administration of rivaroxaban, PMP levels were increased (median, [IQR] 35.7 [28.8-47.3] vs. 48.4 [30.9-82.8] cells/µL; P = 0.012), along with an increase in EMP levels (14.6 [10.0-18.6] vs. 18.3 [12.9-37.1] cells/µL, P < 0.001). In the multivariable regression analysis, the independent predictor of post-dose change in PMPs was statin therapy (HR -0.43; 95% CI -0.75,-0.10, P = 0.011). The post-dose change in EMPs was also predicted by statin therapy (HR -0.34; 95% CI -0.69, -0.01, P = 0.046). This study showed an increase in both EMPs and PMPs at the peak plasma concentration of rivaroxaban. Statins have promising potential in the prevention of rivaroxaban-related PMP and EMP release. The pro-thrombotic role of PMPs and EMPs during rivaroxaban therapy requires further study.

Objectives: To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality., Material and Methods: We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology., Results: During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003)., Conclusions: Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.

Background: Little is known about the prognostic role of fasting glucose after mechanical thrombectomy (MT)., Aims: We investigated whether fasting glucose on the next day after MT was associated with long-term outcome in acute ischemic stroke patients according to diabetes., Methods: We retrospectively analyzed 181 consecutive patients with acute anterior circulation ischemic stroke who underwent MT in 2 comprehensive stroke centers in Poland. Glucose levels were evaluated on admission and on the next day after MT. Fasting hyperglycemia (FHG) was defined as the glucose level above 5.5 mmol/L. Unfavorable outcome was defined as modified Rankin scale (mRS) of 3-6 at day 90 from stroke onset., Results: Patients with FHG had higher mRS at 3-month follow-up compared with those without FHG (3.71 ± 2.56 versus 1.87 ± 2.22, P < .001). In the subgroup analyses, FHG was associated with poor neurological outcome in the group without diabetes (3.74 ± 2.52 versus 1.81 ± 3.74, P < .001) but not with diabetes (3.64 ± 2.67 versus 2.30 ± 3.74, P= .11). Patients without diabetes who had FHG were older, had higher glucose on admission, higher prevalence of atrial fibrillation, cardioembolic stroke etiology and bleeding brain complications compared with the group with normal fasting glucose. After adjustment for potential confounders, fasting glucose (odds ratio [OR] 1.46; 95% CI 1.19-1.79, P < .001), age (OR 1.06; 95% CI 1.02-1.10, P = .001), successful reperfusion (OR 0.09; 95% CI 0.04-0.22, P < .001) and baseline NIHSS score (OR 1.18; 95% CI 1.08-1.29, P < .001) were predictors of mRS 3-6 at 3-month follow-up in the whole group. In the subgroup without diabetes, fasting glucose (OR 1.57; 95% CI 1.17-2.11, P = .002), age (OR 1.05; 95% CI 1.01-1.08, P = .008), successful reperfusion (OR 0.11; 95% CI 0.04-0.30, P < .001) and baseline NIHSS score (OR 1.14; 95% CI 1.04-1.26, P = .011) were independent predictors of unfavorable 3-month outcome., Conclusions: Fasting glucose on the next day after MT in patients with acute ischemic stroke is an independent risk factor for worse 3-month outcome., (Copyright © 2020. Published by Elsevier Inc.)

Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor-based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non-vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF.

Major bleeding (especially intracranial hemorrhage) is the most feared adverse event observed in patients with atrial fibrillation (AF) receiving oral anticoagulation. Clinical risk factor-based scores have modest ability to predict major or clinically relevant bleeds, and blood biomarkers are increasingly implemented to improve bleeding prognostication in patients with AF on life‑long anticoagulation. To improve the safety of anticoagulation in the era of non-vitamin K antagonist oral anticoagulants (NOACs, or direct oral anticoagulants [DOACs], including dabigatran, rivaroxaban, apixaban, and edoxaban), specific demographic, clinical, and laboratory variables should be considered. The current review summarizes practical challenges in the management of oral anticoagulation with emphasis on the risk assessment tools, elderly or underweight patients, cancer patients, impact of chronic kidney disease, liver cirrhosis, and thrombocytopenia in the context of bleeding risk in patients with AF.

Background: Formation of dense fibrin clots has been reported in both atrial fibrillation (AF) and ischemic stroke. We have previously demonstrated that such clot properties can predict thromboembolism and major bleeding in AF patients treated with vitamin K antagonists (VKAs). In this longitudinal cohort study, we evaluated whether impaired fibrinolysis is associated with clinical outcomes in AF., Methods: In 236 patients with AF receiving VKAs, we measured ex vivo plasma clot lysis time (CLT), a measure of global fibrinolysis along, with von Willebrand factor antigen (vWF), plasminogen activator inhibitor 1 antigen (PAI-1), and other fibrinolysis modulators. The primary outcome were ischemic cerebrovascular events. Secondary end points were death and major bleeding., Results: During a median follow-up time of 4.3 (interquartile range 3.7-4.8) years, annual rates of death, ischemic cerebrovascular events, and major bleeding were 1.48%, 2.96%, and 3.45%, respectively. Patients with CLT in the fourth quartile (> 115 min) had 8-fold higher stroke or transient ischemic attack (TIA) rates compared with the other patients (8.67% vs 1.1%; P < 0.0001). CLT correlated with PAI-1 and vWF (r = 0.59; P < 0.0001 for both). In the multivariate Cox regression analysis adjusted for potential confounders, the independent predictors of stroke or TIA were CLT > 115 minutes (hazard ratio [HR] 7.67, 95% confidence interval [CI] 2.78-21.17; P < 0.0001), PAI-1 (HR 1.16, 95% 1.05-1.28; P = 0.003), and CHA 2 DS 2 -VASc score ≥3 (HR 5.18, 95% 1.76-15.29; P = 0.003). CLT was not associated with death or major and minor bleeding events., Conclusions: Impaired fibrinolysis may predict thromboembolic events in AF patients receiving VKA., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Non-vitamin K antagonist oral anticoagulants (NOACs), or direct oral anticoagulants have not been tested in randomized trials conducted in patients with atrial fibrillation (AF), who had malignant disease. However, their use in cancer patients increases and real-life evidence for their effectiveness and safety in this vulnerable subset of patients is growing. The challenges of the use of NOACs in cancer patients with AF and the current expert opinions on this subject have been summarized in this review article.

The prothrombotic state in patients with atrial fibrillation (AF) is related to endothelial injury, the activation of platelets and the coagulation cascade. We evaluated the levels of platelet- (CD42b) and endothelial-derived (CD144) microparticles in the plasma patients with non-valvular AF treated with dabigatran at the time of expected minimum and maximum drug plasma concentrations. Following that, we determined the peak dabigatran plasma concentration (c peak ). CD42b increased after taking dabigatran (median [IQR] 36.7 [29.4-53.3] vs. 45.6 [32.3-59.5] cells/µL; p = 0.025). The concentration of dabigatran correlated negatively with the post-dabigatran change in CD42b (ΔCD42b, r = -0.47, p = 0.021). In the multivariate model, the independent predictors of ΔCD42b were: c peak (HR -0.55; with a 95% confidence interval, CI [-0.93, -0.16]; p = 0.007), coronary artery disease (CAD) (HR -0.41; 95% CI [-0.79, -0.02]; p = 0.037) and peripheral artery disease (PAD) (HR 0.42; 95% CI [0.07, 0.74]; p = 0.019). CD144 did not increase after dabigatran administration. These data suggest that low concentrations of dabigatran may be associated with platelet activation. PAD and CAD have distinct effects on CD42b levels during dabigatran treatment.

Background and Purpose: Atrial fibrillation (AF) has a progressive nature, leading to structural, functional, and electrical changes in the left atrium (LA). Enhanced response to treatment in patients with AF can be achieved through improved knowledge of atrial structure and a better understanding of its function. The aim of this study was to assess LA strain and its determinants in patients with paroxysmal (PAF), persistent (PsAF), and permanent AF (PmAF)., Methods: Fifty-eight patients with registered non-valvular AF were divided into 3 groups depending on the type of AF. The participants underwent transthoracic echocardiography to assess the anatomy and function of heart chambers. Left atrial longitudinal strain (LALS) was measured in four-chamber projections using two-dimensional speckle tracking echocardiography., Results: Patients with PAF had higher LALS (15.7±12.0) when compared to those with PsAF (4.3±7.9) and PmAF (5.8±7.8, all P=0.003). Multiple linear regression showed that the independent predictors of LALS were diastolic blood pressure (β=0.95, R2=0.88) in the PAF group; left atrial area (β=-0.56) and creatinine (β=-0.63, R2=0.58) in the PsAF group; AF duration (β=0.89) in the PmAF group (R2=0.72)., Conclusion: LA strain has different determinants depending on AF type. LA size, renal function, and AF duration determine LALS in long-lasting AF. LA strain is a simple and accurate technique to estimate LA dysfunction in patients with long-lasting AF.

BACKGROUND Neurogenic mechanism is believed to contribute to left ventricular (LV) systolic dysfunction in acute coronary syndromes (ACS); its extreme form is known as takotsubo cardiomyopathy. However, the magnitude of neurogenic contribution to LV dysfunction in all-comer first-time ACS remains unknown. MATERIAL AND METHODS In 120 consecutive patients with first-time ACS (age 66.3±12.3years, 40 women) coronary angiograms were individually matched to the echocardiographic left ventricular (LV) segments (17-segment model). Baseline contractility impairment was classified as ischemic (I): confined to the stenotic artery(ies) supply area(s), neurogenic (N): in absence of attributable coronary stenosis, or partially ischemic/partially neurogenic (I&N). Echocardiography was repeated at 6 months to determine LV systolic function recovery. RESULTS Neurogenic component (NC) contribution to myocardial contractility impairment was present in 24.2% of ACS patients, with pure N in 6.7% and I&N in 17.5%. Diabetes/pre-diabetes was present in 38.5% vs. 33.5% vs. 0% (I vs. I&N vs. N; p=0.02). Major stressor preceding symptom onset was reported in 3.3% in I, 9.5% in I&N, and 25.0% in N (p=0.03). The number of LV segments with contractility impairment was 2±4 in I, 17±11 in I&N, and 3±16 in N (p<0.05). NC presence was independently associated with better recovery of global LV systolic function (OR 2.99, 95% CI: 1.16-7.76; p=0.024). CONCLUSIONS Novel findings from this study are: (1) NC may contribute to myocardial contractility impairment in 1 in every 4 first-time ACS patients, (2) NC contribution to contractility impairment in ACS is blunted in diabetes or pre-diabetes, and (3) LV systolic function recovery is better in patients with NC.

Background and Purpose: Formation of denser fiber networks has been reported in atrial fibrillation and ischemic stroke. In this longitudinal cohort study, we evaluated whether fibrin clot density may predict thromboembolic and bleeding risk in patients with atrial fibrillation on vitamin K antagonists., Methods: In 236 patients with atrial fibrillation receiving vitamin K antagonists treatment, we measured ex vivo plasma clot permeability (K s ), a measure of the pore size in fibrin networks., Results: During a median follow-up of 4.3 (interquartile range, 3.7-4.8) years, annual rates of ischemic stroke or transient ischemic attack and major bleeds were 2.96% and 3.45%, respectively. In multivariate Cox regression analysis, patients with lower K s (<6.8 cm 2 ×10 -9 , median) had increased risk of ischemic stroke or transient ischemic attack (hazard ratio [HR], 6.55; 95% confidence interval [CI], 2.17-19.82) and major bleeds (HR, 10.65; 95% CI, 3.52-32.22). Patients with elevated K s (≥6.8 cm 2 ×10 -9 ) had an increased rate of minor bleeding compared with the remainder (11.63% per year versus 3.55% per year; P <0.0001). The independent predictors of stroke or transient ischemic attack were low K s (<6.8 cm 2 ×10 - 9 ; HR, 7.24; 95% CI, 2.53-20.76), age (HR, 1.05; 95% CI, 1.01-1.10), and treatment with angiotensin-converting enzyme inhibitors (HR, 2.27; 95% CI, 1.08-4.77). Major bleeds were predicted by low K s (<6.8 cm 2 ×10 -9 ; HR, 8.48; 95% CI, 2.99-24.1) and HAS-BLED score ≥3 (HR, 2.22; 95% CI, 1.12-4.38)., Conclusions: This study is the first to show that unfavorable fibrin properties reflected by formation of denser fibrin networks determine, in part, the efficacy and safety of anticoagulation with vitamin K antagonists in patients with atrial fibrillation., (© 2017 American Heart Association, Inc.)

Coronary artery disease (CAD) remains a major cause of death in developed countries. Both environmental and, less known, genetic factors contribute to progression of CAD to myocardial infarction (MI). Immune system is activated in patients with CAD through dendritic cells (DCs), which present plaque antigens to T lymphocytes. Production of proinflammatory cytokines by activated T cells contributes to plaque rupture in MI. Chemokine receptor 7 (CCR7) on DCs is required for their chemotaxis from plaque to lymph nodes. This makes possible an interaction of DCs with T lymphocytes and initiation of specific immune response. We hypothesized that single nucleotide polymorphisms (SNPs) in CCR7 gene locus are associated with previous MI in patients with CAD. To test this hypothesis, we genotyped six SNPs from the CCR7 gene locus in 300 consecutive patients, admitted for elective coronary angiography. We performed univariate-, multivariate- (including potential confounders) and haplotype-based tests of association of SNPs with previous MI and results of angiography. Allele A of rs17708087 SNP was associated with previous MI. This association remained significant after adjustment for age, sex, smoking, hypercholesterolaemia and drugs used by patients (odds ratio 2.13, 95% confidence interval: 1.13-3.86). Therefore, we conclude that CCR7 gene locus harbours a polymorphism that modifies risk of MI in patients with CAD. Replication of this association could be sought in a prospective cohort of initially healthy individuals., (© 2016 John Wiley & Sons Ltd.)

Introduction: Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF)., Material and Methods: We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins., Results: Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower Ks (-7.7%, P=0.01; -8.6%, P=0.005, respectively) and prolonged CLT (+10.8%, P=0.006; +7.8% P=0.04, respectively). No associations of Ks and CLT with CHA2DS2-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β=-0.41), vWF (β=-0.29) and PF4 (β=-0.28) are the independent predictors of Ks (R(2)=0.78), while CLT was independently predicted by TG (β=0.37), PAI-1 antigen (β=0.29) and vWF (β=0.26) in the AF group (R(2)=0.39)., Conclusions: Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Patients who have undergone a Fontan operation (FO) may suffer from both systolic and diastolic single ventricle (SV) dysfunction., Aim: The aim of the study was to quantify non-invasively the systolic and diastolic single ventricle function in adult FO patients and to assess its effect on exercise tolerance., Methods: We investigated 21 patients (12F; 9M) after FO with morphological left ventricle with a mean age of 26 +/- 6 years, and 17 age-matched, healthy people (control group). Pulse-wave Doppler signals from the mitral inflow, aortic flow and tissue Doppler imaging of the mitral annulus were obtained. A cardiopulmonary exercise test (CPET) was performed., Results: The Fontan patients, as compared to the controls, had a lower value of SV ejection fraction (SVEF), E velocity, E/A ratio, aortic valve velocity time integral, exercise time, SatO2, VO(2peak) and significantly higher E/E' ratio, VE/VCO(2peak) and VE/VO(2peak'). We found negative correlations between E/E' and exercise time and VO(2peak). Positive correlations were found between E/E' and VE/VCO(2peak) and age at surgery. S' velocity correlated positively with SVEF, VO(2peak) and negatively with E/E' ratio. Patients after FO with E/E' ratio > or = 12 had a significantly lower oxygen uptake when compared to those with E/E' ratio < 12., Conclusion: Adult patients after Fontan operations are characterized by both systolic and diastolic dysfunction of the single ventricle, associated with severe exercise intolerance reflected by shorter duration of exercise with decreased oxygen uptake and increased ventilatory response. E/E' ratio assessed by Tissue Doppler echocardiography can be a powerful predictor of oxygen uptake and ventilatory response.

Background: Gradual impairment of exercise tolerance is the commonest sign of heart failure (HF). Little is known as to which cardiac contributors of poor exercise capacity carry an independent prognostic information in HF., Aim: We investigated the prognostic role of exercise echocardiography (ex-echo) in HF patients., Methods: We studied 85 consecutive, symptomatic HF patients (66 males, mean age 62.5 ± 11.8 [range 21-83] years, mean left ventricular ejection fraction [LVEF] 27.2 ± 9.5%). The end-point was all-cause mortality. During the follow-up period (mean 43 ± 21 months) 21 patients died. Resting echocardiography and ex-echo, with the simultaneous measurement of peak oxygen uptake (VO(2peak)), was performed in each patient using a semi-supine ergometer (20 W, 2-min increments). Apart from conventional assessment of systolic and diastolic function (EF, E/A, DT, IVRT) or right ventricular systolic pressure (RVSP), tissue Doppler imaging was used for the assessment of LV and RV peak velocity (IVV) as well as acceleration during isovolumic contraction (IVA), peak velocity during ejection phase (S'), peak early diastolic velocity (E'), peak late diastolic velocity (A'), and ratio of early diastolic mitral/tricuspid velocity to peak early diastolic velocity (E/E')., Results: Patients who died were significantly older, had lower exercise capacity, more advanced HF, greater impairment of baseline systolic function, higher baseline pulmonary artery systolic pressure, and most importantly a lack of improvement in EF, diastolic function, and further increase of RVSP during exercise. Out of all echocardiographic parameters, only peak stress EF (x(2) 6.1; p = 0.01), baseline and peak exercise RVSP (x(2) 12.5 and c(2) 18.7; p 〈 0.001; respectively), and mitral E/E' ratio (x(2) 8.9; p 〈 0.01) were univariate predictors of prognosis and remained independently prognostic when adjusted for age and sex but were eliminated from the model by NT-proBNP., Conclusions: During exercise, more severe systolic and diastolic dysfunction with the elevation of pulmonary arterial pressure is more prevalent in HF patients who have a poorer outcome. The estimation of common parameters such as EF, RVSP and E/E' using ex-echo, provides prognostic information in HF.

The metabolism of renin-angiotensin system (RAS) is more complicated than previously expected and understanding the biological phenomena regulated by variety of angiotensin metabolites requires their precise and possibly comprehensive quantitation. Physiological concentrations of angiotensins (Ang) in biological fluids are low, therefore their accurate measurements require very sensitive and specific analytical methods. In this study we developed an accurate and reproducible method of quantitation of angiotensin metabolites through coupling of liquid chromatography and electrospray ionization - mass spectrometry (LC-ESI-MS). With this method main angiotensin metabolites (Ang I, II, III, IV, 1-9, 1-7, 1-5) can be reliably measured in organ bath of rat tissues (aorta, renal artery, periaortal adipose tissue) and in medium of cultured endothelial cells (EA.hy926), exposed to Ang I for 15 minutes, in the absence or in the presence of angiotensin converting enzyme inhibitor, perindoprilat. Presented LC-ESI-MS method proved to be a quick and reliable solution to comprehensive analysis of angiotensin metabolism in biological samples.