The role of glial autophagy in Alzheimer's disease.

Although Alzheimer's disease is the most pervasive neurodegenerative disorder, the mechanism underlying its development is still not precisely understood. Available data indicate that pathophysiology of this disease may involve impaired autophagy in glial cells. The dysfunction is manifested as reduced ability of astrocytes and microglia to clear abnormal protein aggregates. Consequently, excessive accumulation of amyloid beta plaques and neurofibrillary tangles activates microglia and astrocytes leading to decreased number of mature myelinated oligodendrocytes and death of neurons. These pathologic effects of autophagy dysfunction can be rescued by pharmacological activation of autophagy. Therefore, a deeper understanding of the molecular mechanisms involved in autophagy dysfunction in glial cells in Alzheimer's disease may lead to the development of new therapeutic strategies. However, such strategies need to take into consideration differences in regulation of autophagy in different types of neuroglia.

PECAM-1/Thrombus Ratio Correlates with Blood Loss during Off-Pump Coronary Artery Bypass Grafting (OPCAB) Surgery: A Preliminary Study.

Platelet endothelial cell adhesion molecule 1 (PECAM-1) is considered an antiplatelet molecule. Previously, we introduced a new parameter called the PECAM-1/thrombus ratio, which indicates the proportion of PECAM-1 in the thrombus and provides a precise description of human platelet activity (in vitro). The aim of this study was to determine whether the PECAM-1/thrombus ratio could serve as a predictive factor for bleeding events during off-pump coronary artery bypass grafting (OPCAB). To achieve this, we collected blood samples from 20 patients scheduled to undergo OPCAB surgery. We assessed the PECAM-1/thrombus ratio by evaluating thrombus formation on collagen fibers under flow conditions. Subsequently, we compared the ability of the PECAM-1/thrombus ratio in predicting bleeding risk with other methods that evaluate hemostasis activity. These methods included assessing platelet P-selectin secretion, platelet exposure of phosphatidylserine, plasma coagulation and fibrinolysis system activity, and thrombus formation using the T-TAS assay. Our findings revealed a positive correlation between the PECAM-1/thrombus ratio and the amount of blood component units transfused (BCUT) during the OPCAB surgery. Furthermore, BCUT did not show any significant correlation with other measured hemostasis parameters. This preliminary study suggests that the PECAM-1/thrombus ratio might be a good predictor of bleeding risk during the OPCAB procedure.

Bilateral subdiaphragmatic vagotomy modulates the peripheral met­enkephalin and striatal monoamine responses to peripheral inflammation in rat.

In the central nervous system, long­term effects of a vagotomy include disturbance of monoaminergic activity of the limbic system. Since low vagal activity is observed in major depression and autism spectrum disorder, the study aimed to determine whether animals fully recovered after subdiaphragmatic vagotomy demonstrates neurochemical indicators of altered well­being and social component of sickness behavior. Bilateral vagotomy or sham surgery was performed in adult rats. After one month of recovery, rats were challenged with lipopolysaccharide or vehicle to determine the role of central signaling upon sickness. Striatal monoamines and met­enkephalin concentrations were evaluated using HPLC and RIA methods. We also defined a concentration of immune­derived plasma met­enkephalin to establish a long­term effect of vagotomy on peripheral analgesic mechanisms. The data indicate that 30 days after vagotomy procedure, striatal dopaminergic, serotoninergic, and enkephalinergic neurochemistry was altered, both under physiological and inflammatory conditions. Vagotomy prevented inflammation­induced increases of plasma met­enkephalin - an opioid analgesic. Our data suggest that in a long perspective, vagotomized rats may be more sensitive to pain and social stimuli during peripheral inflammation.

Overnight Corticosterone and Gene Expression in Mouse Hippocampus: Time Course during Resting Period.

The aim of the experiment was to test the effect of an elevated level of glucocorticoids on the mouse hippocampal transcriptome after 12 h of treatment with corticosterone that was administered during an active phase of the circadian cycle. Additionally, we also tested the circadian changes in gene expression and the decay time of transcriptomic response to corticosterone. Gene expression was analyzed using microarrays. Obtained results show that transcriptomic responses to glucocorticoids are heterogeneous in terms of the decay time with some genes displaying persistent changes in expression during 9 h of rest. We have also found a considerable overlap between genes regulated by corticosterone and genes implicated previously in stress response. The examples of such genes are Acer2, Agt, Apod, Aqp4, Etnppl, Fabp7, Fam107a, Fjx1, Fmo2, Galnt15, Gjc2, Heph, Hes5, Htra1, Jdp2, Kif5a, Lfng, Lrg1, Mgp, Mt1, Pglyrp1, Pla2g3, Plin4, Pllp, Ptgds, Ptn, Slc2a1, Slco1c1, Sult1a1, Thbd and Txnip. This indicates that the applied model is a useful tool for the investigation of mechanisms underlying the stress response.

Hypothalamic Neurochemical Changes in Long-Term Recovered Bilateral Subdiaphragmatic Vagotomized Rats.

Background: Vagus nerve is one of the crucial routes in communication between the immune and central nervous systems. The impaired vagal nerve function may intensify peripheral inflammatory processes. This effect subsides along with prolonged recovery after permanent nerve injury. One of the results of such compensation is a normalized plasma concentration of stress hormone corticosterone - a marker of hypothalamic-pituitary-adrenal (HPA) axis activity. In this work, we strive to explain this corticosterone normalization by studying the mechanisms responsible for compensation-related neurochemical alterations in the hypothalamus. Materials and Methods: Using microarrays and high performance liquid chromatography (HPLC), we measured genome-wide gene expression and major amino acid neurotransmitters content in the hypothalamus of bilaterally vagotomized rats, 1 month after surgery. Results: Our results show that, in the long term, vagotomy affects hypothalamic amino acids concentration but not mRNA expression of tested genes. Discussion: We propose an alternative pathway of immune to CNS communication after vagotomy, leading to activation of the HPA axis, by influencing central amino acids and subsequent monoaminergic neurotransmission.

Dissection of Mouse Hippocampus with Its Dorsal, Intermediate and Ventral Subdivisions Combined with Molecular Validation.

Many research methods applied in molecular neuroscience require the collection of hippocampal samples, but a still poorly recognized problem is contamination with the choroid plexus during brain dissection. Because of a distinct pattern of gene expression, its inclusion in brain samples can obscure or even confound conclusions drawn from molecular studies. Therefore, we tested our dissection method designed for removal of tissue contamination using expression of the transthyretin gene (Ttr) as a marker of the choroid plexus. Additionally, we also validated dissection of the entire hippocampus into its dorsal, intermediate and ventral subdivisions using the expression of Trhr and Lct genes as molecular markers of anatomical subdivisions. The PCR analysis showed that Ttr is expressed at a residual level in hippocampal samples that display an mRNA level several hundred lower than the adjacent control tissue colocalized with the choroid plexus. This indicates that the applied method for dissecting the hippocampus from a fresh brain allows for replicable removal of the majority of choroid plexus from hippocampal samples. In turn, differences in expression of Lct and Trhr confirmed the proper dissection of dorsal, intermediate and ventral subdivisions from fresh brain tissue. Therefore, a special emphasis on the removal of tissue contamination and avoidance of tissue distortions makes our protocol especially suitable for molecular experiments performed either on the entire hippocampus or its subdivisions.

Stress and the brain transcriptome: Identifying commonalities and clusters in standardized data from published experiments.

Interpretation of transcriptomic experiments is hindered by many problems including false positives/negatives inherent to big-data methods and changes in gene nomenclature. To find the most consistent effect of stress on brain transcriptome, we retrieved data from 79 studies applying animal models and 3 human studies investigating post-traumatic stress disorder (PTSD). The analyzed data were obtained either with microarrays or RNA sequencing applied to samples collected from more than 1887 laboratory animals and from 121 human subjects. Based on the initial database containing a quarter million differential expression effect sizes representing transcripts in three species, we identified the most frequently reported genes in 223 stress-control comparisons. Additionally, the analysis considers sex, individual vulnerability and contribution of glucocorticoids. We also found an overlap between gene expression in PTSD patients and animals which indicates relevance of laboratory models for human stress response. Our analysis points to genes that, as far as we know, were not specifically tested for their role in stress response (Pllp, Arrdc2, Midn, Mfsd2a, Ccn1, Htra1, Csrnp1, Tenm4, Tnfrsf25, Sema3b, Fmo2, Adamts4, Gjb1, Errfi1, Fgf18, Galnt6, Slc25a42, Ifi30, Slc4a1, Cemip, Klf10, Tom1, Dcdc2c, Fancd2, Luzp2, Trpm1, Abcc12, Osbpl1a, Ptp4a2). Provided transcriptomic resource will be useful for guiding the new research.

Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets.

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.

Blastomere removal affects homeostatic control leading to obesity in male mice.

Preimplantation embryos are particularly vulnerable to environmental perturbations, including those related to assisted reproductive technologies. Invasive embryo manipulations, such as blastomere biopsy, are applied worldwide in clinical settings for preimplantation genetic testing. Mouse models have previously shown that blastomere biopsy may be associated with altered phenotypes in adult offspring. The aim of the present study was to investigate the specific contribution of blastomere removal to the physiological, behavioral, and molecular regulators of energy homeostasis, as compared to sham manipulation (re-introducing the blastomere into the embryo after its removal) and in vitro culture. Mice derived from 8-cell embryos subjected to blastomere removal displayed: (i) higher body weight and adiposity, (ii) increased food intake and sucrose preference, (iii) decreased time of immobility in the tail suspension test, and (iv) resistance to weight loss after social isolation or following 3 days of physical exercise - compared to mice derived from sham biopsy or from in vitro-cultured embryos. Mice generated after blastomere removal also had increased circulating leptin and leptin gene expression in adipose tissue, as well as increased ghrelin receptor gene expression in the hypothalamus, compared to control mice. The effects of blastomere biopsy on offspring phenotype were sexually dimorphic, with females not being affected. These results indicate that blastomere deprivation, rather than other perturbations of the blastomere biopsy procedure, programs male embryos to develop physiological, behavioral, and molecular dysregulation of energy homeostasis, leading to postnatal obesity.

Assessing the epigenetic risks of assisted reproductive technologies: a way forward.

Since the birth of the first baby conceived by in vitro fertilization (IVF), assisted reproductive technologies (ART) have been constantly evolving to accomodate needs of a growing number of infertile couples. Rapidly developing ART procedures are directly applied for human infertility treatment without prior long-term safety evaluation. Although the majority of ART babies are healthy at birth, a comprehensive assessment of the long-term risks associated with ART is still lacking. An increased risk of epigenetic errors has been associated with the use of ART, which may contribute to the onset of civilization disease later in adolescence/adulthood and/or in subsequent generations. Therefore, our investigations should not focus on (or be limited to) the occurrence of a few very rare imprinting disorders in ART children, which might be associated with parental age and/or the use of ART, but on the possibly increased disease susceptibilities later in life and their potential transmission to the subsequent generations. Retrospective studies do not offer exhaustive information on long-term consequences of ART. Animal models are useful tools to study long-term effects including transgenerational ones and the epigenetic risk of a given ART procedure, which could then be translated to the human context. The final goal is the establishment of common guidelines for assessing the epigenetic risk of ART in humans, which will contribute to two key objectives of the Horizon2020 programme, i.e. to improve our understanding of the causes and mechanisms underlying health and disease, and to improve our ability to monitor health and prevent/manage disease.

Graphene oxide down-regulates genes of the oxidative phosphorylation complexes in a glioblastoma.

BACKGROUND: Recently different forms of nanographene were proposed as the material with high anticancer potential. However, the mechanism of the suppressive activity of the graphene on cancer development remains unclear. We examined the effect of oxygenated, reduced and pristine graphene on the gene expression in glioblastoma U87 cell line. RESULTS: Conducting microarrays and RT-qPCR analysis we explored that graphene oxide (rather than reduced graphene oxide and pristine graphene) down-regulates the mRNA expression of mitochondrial oxidative phosphorylation (OXPHOS) nuclear genes of complexes I, III, IV and V. The presented results provide first evidence for the hypothesis that the suppressed growth of GBM can be the consequence of down-regulation of OXPHOS protein expression and decreased ATP level. CONCLUSIONS: We suggest that changes in the expression of OXPHOS genes identified in our study may mediate the anti-proliferative and anti-migratory effects of graphene oxide in glioblastoma cells. However, further investigations with different cell lines, regarding expression, regulation and activity of OXPHOS genes identified in our study is necessary to elucidate the mechanism mediating the anti-proliferative and anti-migratory effects of graphene oxide in glioblastoma cells.

Molecular neuroscience at its "high": bibliometric analysis of the most cited papers on endocannabinoid system, cannabis and cannabinoids.

BACKGROUND: Cannabis, cannabinoids and endocannabinoids are heavily investigated topics with many articles published every year. We aimed to identify the 100 most cited manuscripts among the vast literature and analyze their contents. METHODS: Web of Science (WoS) Core Collection was searched to identify the 100 most cited relevant manuscripts, which were analyzed with reference to (1) authorship, (2) institution, (3) country, (4) document type, (5) journal, (6) publication year, (7) WoS category, and (8) citation count. Semantic content and citation data of the manuscripts were analyzed with VOSviewer. RESULTS: The most cited manuscripts were published between 1986 and 2016, with the majority being published in the 2000s (n = 51). The number of citations for the top 100 articles ranged from 469 to 3651, with a median citation count of 635.5. The most prolific authors were Vincenzo Di Marzo (n = 11) and Daniele Piomelli (n = 11). The major contributing countries were USA (n = 49), Italy (n = 22), UK (n = 19), and France (n = 11). The most prolific institutions were University of California (n = 14), National Research Council of Italy (n = 12) and National Institutes of Health USA (n = 12). The manuscripts consisted of original articles (n = 75), reviews (n = 24) and a note (n = 1). The most dominant journal was Nature (n = 15). The major WoS categories associated were Multidisciplinary sciences (n = 31), Neurosciences (n = 20), Pharmacology / Pharmacy (n = 16), and General / Internal Medicine (n = 11). CONCLUSIONS: The top-ranked manuscripts among the 100 were concerning analgesia, weight loss, long-term potentiation, depolarization-induced suppression of inhibition, opiates and other topics. Cannabinoid type 1 (CB1) receptor was studied by more of the top 100 papers in comparison to cannabinoid type 2 (CB2) receptor. The most frequently mentioned chemicals in these publications were 2-arachidonoylglycerol, tetrahydrocannabinol, and anandamide. Together, these manuscripts comprise the most highly cited publications in the topic, literally the molecular neuroscience at its "high".

Autophagy and Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Implications.

Alzheimer's disease (AD) is the most common cause of progressive dementia in the elderly. It is characterized by a progressive and irreversible loss of cognitive abilities and formation of senile plaques, composed mainly of amyloid ß (Aß), and neurofibrillary tangles (NFTs), composed of tau protein, in the hippocampus and cortex of afflicted humans. In brains of AD patients the metabolism of Aß is dysregulated, which leads to the accumulation and aggregation of Aß. Metabolism of Aß and tau proteins is crucially influenced by autophagy. Autophagy is a lysosome-dependent, homeostatic process, in which organelles and proteins are degraded and recycled into energy. Thus, dysfunction of autophagy is suggested to lead to the accretion of noxious proteins in the AD brain. In the present review, we describe the process of autophagy and its importance in AD. Additionally, we discuss mechanisms and genes linking autophagy and AD, i.e., the mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, and UCHL1. We also present pharmacological agents acting via modulation of autophagy that may show promise in AD therapy. This review updates our knowledge on autophagy mechanisms proposing novel therapeutic targets for the treatment of AD.

Ethnopharmacological Approaches for Dementia Therapy and Significance of Natural Products and Herbal Drugs.

Dementia is a clinical syndrome wherein gradual decline of mental and cognitive capabilities of an afflicted person takes place. Dementia is associated with various risk factors and conditions such as insufficient cerebral blood supply, toxin exposure, mitochondrial dysfunction, oxidative damage, and often coexisting with some neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). Although there are well-established (semi-)synthetic drugs currently used for the management of AD and AD-associated dementia, most of them have several adverse effects. Thus, traditional medicine provides various plant-derived lead molecules that may be useful for further medical research. Herein we review the worldwide use of ethnomedicinal plants in dementia treatment. We have explored a number of recognized databases by using keywords and phrases such as "dementia", "Alzheimer's," "traditional medicine," "ethnopharmacology," "ethnobotany," "herbs," "medicinal plants" or other relevant terms, and summarized 90 medicinal plants that are traditionally used to treat dementia. Moreover, we highlight five medicinal plants or plant genera of prime importance and discuss the physiological effects, as well as the mechanism of action of their major bioactive compounds. Furthermore, the link between mitochondrial dysfunction and dementia is also discussed. We conclude that several drugs of plant origin may serve as promising therapeutics for the treatment of dementia, however, pivotal evidence for their therapeutic efficacy in advanced clinical studies is still lacking.

Glucocorticoids, genes and brain function.

The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1). The GC-induced reprogramming of cell function involves changes in the mRNA level of genes responsible for the regulation of transcription (Klf9, Bcl6, Klf15, Tle3, Cxxc5, Litaf, Tle4, Jun, Sox4, Sox2, Sox9, Irf1, Sall2, Nfkbia and Id1) and the selective degradation of mRNA (Tob2). Other genes are involved in the regulation of metabolism (Gpd1, Aldoc and Pdk4), actin cytoskeleton (Myh2, Nedd9, Mical2, Rhou, Arl4d, Osbpl3, Arhgef3, Sdc4, Rdx, Wipf3, Chst1 and Hepacam), autophagy (Eva1a and Plekhf1), vesicular transport (Rhob, Ehd3, Vps37b and Scamp2), gap junctions (Gjb6), immune response (Tiparp, Mertk, Lyve1 and Il6r), signaling mediated by thyroid hormones (Thra and Sult1a1), calcium (Calm2), adrenaline/noradrenaline (Adcy9 and Adra1d), neuropeptide Y (Npy1r) and histamine (Hdc). GCs also affected genes involved in the synthesis of polyamines (Azin1) and taurine (Cdo1). The actions of GCs are restrained by feedback mechanisms depending on the transcription of Sgk1, Fkbp5 and Nr3c1. A side effect induced by GCs is increased production of reactive oxygen species. Available data show that the brain's response to GCs is part of an emergency mode characterized by inactivation of non-core activities, restrained inflammation, restriction of investments (growth), improved efficiency of energy production and the removal of unnecessary or malfunctioning cellular components to conserve energy and maintain nutrient supply during the stress response.

Pregnancy at Advanced Maternal Age Affects Behavior and Hippocampal Gene Expression in Mouse Offspring.

There is growing evidence that advanced maternal age is a risk factor for neurological and neuropsychiatric disorders in offspring. However, it remains unclear whether the altered brain programming induced by advanced maternal age is mediated by pre- or postnatal factors. Here, a mouse model was used to investigate whether pregnancy at advanced age may provoke behavioral and brain gene expression changes in offspring. Swiss Albino mice conceived by 3-month-old males and either 15-18-month-old (n = 11) or 3-month-old control females (n = 5), were delivered by cesarean section, fostered after birth by 3-month-old dams and subjected to a battery of behavioral tests. Furthermore, genome-wide mRNA expression was analyzed in the hippocampi of 4-month-old males offspring using microarrays. Offspring conceived by old mothers exhibited increased ultrasound vocalization activity during separation from the foster mother, increased anxiety-like behaviors in adult life, and altered patterns of hippocampal gene expression, compared to controls. These effects were not reversed by the postnatal maternal care provided by the young foster mothers, suggesting that the altered brain programming is already established at birth, consistent with prenatal effects related to maternal aging.

Quinapril decreases antifibrinolytic and prooxidative potential of propofol in arterial thrombosis in hypertensive rats.

Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on hemodynamics and hemostasis in renal-hypertensive rats with induced arterial thrombosis. Two-kidney, one clip hypertensive rats were treated with quinapril (3.0 mg/kg for 10 days), and then received propofol infusion (15 mg/kg/h) during ongoing arterial thrombosis. The hemodynamic and hemostatic parameters were assayed. Quinapril exerted a hypotensive effect increasing after propofol infusion. Quinapril showed an antithrombotic effect with the platelet adhesion reduction, fibrinolysis enhancement and oxidative stress reduction. Propofol did not influence thrombosis; however, it inhibited fibrinolysis and showed prooxidative action. The effect of propofol on fibrinolysis and oxidative stress was significantly lower in quinapril-pretreated rats. Mortality was increased among rats treated with both drugs together. Our study demonstrates that pretreatment with quinapril reduced the adverse effects of propofol on hemostasis. Unfortunately, co-administration of both drugs potentiated hypotension in rats, which corresponds to higher mortality.

Single-centre experience in surgery of acute aortic type A dissection and true aortic arch aneurysm.

BACKGROUND: Surgery of the aortic arch is challenging. AIM: To assess the results of aortic arch surgery. METHODS: Analysis of 172 patients operated on arch dissection (emergency group: 97 patients) or aneurysm (elective group: 75 patients) between 2007 and 2014. Arch surgery was defined as a procedure requiring circumferential anastomosis at the level of the aortic arch or the descending aorta with the use of techniques of brain protection (deep hypothermic circulatory arrest [DHCA] or selective antegrade cerebral perfusion [SACP]) and/or debranching of at least one supra-aortic vessel. RESULTS: Men predominated in both groups (> 70%). Men were younger in the emergency group (55 vs. 66 years; p < 0.008). The operative risk was higher in the emergency group (19.2% vs. 12.5%; p < 0.001). Forty-nine per cent of the patients from the emergency group and 5% from the elective group were operated with antiplatelet therapy (p < 0.001). Extended hemiarch procedure was performed in 79% (n = 77) in the emergency and 76% (n = 57) in the elective group. Total arch replacement was performed in 19 (21%) patients from the emergency and 18 (24%) patients from the elective group. In these patients debranching was performed in 68% of the emergency patients group and in 67% of the elective group. Elephant trunk procedure (classic/frozen) was performed in 53% (n = 10) from the emergency and in 78% (n = 14) of patients from the elective group. Aortic valve sparing surgery was performed in 20% of patients from the emergency and 9% from the elective group (p = 0.063). DHCA was performed in 58% (n = 43) of patients from the elective group and 39% (n = 37) from the emergency group. SACP was performed in 61% (n = 58) of patients from the emergency and 42% (n = 31) from the elective group. Thirty-day mortality in the emergency group reached 33% (n = 32), and in the elective group 15% (n = 11; p = 0.007). In multivariate analysis, predictors of death in the emergency group were: Logistic EuroSCORE above 19.5%, extracorporeal circulation time above 228 min, and postoperative acute renal failure (ARF); and in the elective group: DHCA time above 26 min, rethoracotomy due to bleeding, and ARF. Follow-up was completed in 100% of patients in terms of vital status. The mean follow-up time of the patients from the emergency group was 24.3 ± 27.10 (min 0, max 92) months, and from the elective group 30.3 ± 24.5 (min 0, max 99) months. During the follow-up period all-cause mortality in the emergency group was 43% (n = 42/97), and in the elective group it was 36% (n = 27/75). CONCLUSIONS: Early mortality in the emergency group was higher, while long-term mortality did not differ among the groups. Postoperative ARF is a critical predictor of mortality in both groups.