Ампутация ушка левого предсердия с использованием эндостеплера при торакоскопической аблации фибрилляции предсердий

Highlights. Stroke prevention in patients with atrial fibrillation is extremely important and difficult. Lifelong anticoagulant therapy is not always an effective way of preventing thrombosis in the left atrial appendage in this group of patients. In this regard, one of the most urgent problems of modern surgical arrhythmology and cardiac surgery is the search for new open and minimally invasive surgical methods of excluding the left atrial appendage from the blood flow.Aim. To investigate the safety and efficacy of using the left atrial appendage stapler for video-guided thoracoscopic ablation (TSA) of non-valvular atrial fibrillation (AF).Methods. The retrospective, single-center study included 100 patients with non-valvular AF who underwent video-guided thoracoscopic ablation of AF with single-stage left atrial appendage exclusion using an Endo GIA stapler (Medtronic, Minneapolis, Minnesota, USA).Results. The mean age of the patients was 56,2±8,8 years, the majority of the patients (73 patients, 73%) were male. Patients with persistent 50 (50%) AF and longstanding AF 50 (50%) were included in the study. The duration of atrial fibrillation was 4 (1,7–7) years. The median CHA2DS2-VASc and HAS-BLED scores were 2 (1–1,5) and 1 (0-1), respectively. The mean anticoagulation therapy-to-ablation time was 4,2±1,9 years. Thirty-eight (38%) patients were prescribed warfarin preoperatively. The completeness of left atrial appendage (LAA) exclusion was confirmed by intraoperative transesophageal echocardiography. The average length of the staple lines was 48 (35–75). A single left atrial appendage exclusion was performed using a 60 mm staples. In 12 (12%) patients, stapler exclusions were performed using two 45 mm staples due to insufficient staple length. None of the patients had ruptures, punctures along the staple lines or rupture of the surrounding epicardial tissue. Anticoagulant therapy was discontinued 6 months after TSA in 70 (70%) patients with sustained sinus rhythm observed on 24-h Holter Monitoring, satisfactory CHA2DS2-VASc scores and after confirmation of absence of left atrial thrombus by transesophageal echocardiography and contrast-enhanced MSCT. No strokes were reported within 1,2±0,7 years after discontinuing anticoagulation therapy.Conclusion. Exclusion of LAA using a stapler for TSA is a highly effective and safe technique for patients with non-valvular atrial fibrillation compared to alternative methods of excluding the LAA from the systemic blood flow.Основные положения. Профилактика инсультов ишемического генеза у пациентов с фибрилляцией предсердий крайне важная и сложная задача. Пожизненный прием антикоагулянтных препаратов не всегда эффективен в предотвращении тромбообразования в ушке левого предсердия у данной группы больных. В связи с этим актуальной проблемой современной аритмологии и кардиохирургии становится поиск безопасных хирургических и минимально инвазивных методов изоляции ушка левого предсердия из системного кровотока.Цель. Изучить безопасность и эффективность применения режуще-сшивающего эндостеплера для ампутации ушка левого предсердия (УЛП) при видеоассистированной торакоскопической аблации (ТА) неклапанной фибрилляции предсердий (ФП).Материалы и методы. Проведено ретроспективное одноцентровое исследование с проспективным компонентом с включением 100 пациентов с неклапанной ФП, которым выполнено видеоассистированное торакоскопическое лечение ФП с одномоментной ампутацией УЛП при помощи режуще-сшивающего механизированного эндостеплера EndoGIA (Medtronic, США).Результаты. Средний возраст больных составил 56,2±8,8 года, преобладали мужчины – 73 (73%). В исследование включены лица с персистирующей, n = 50 (50%), и длительно персистирующей ФП – 50 (50%). Длительность ФП составила 4 (1,7‒7) года. Медиана значений по шкалам CHA2DS2-VASc и HAS-BLED – 2 (1–1,5) и 1 (0–1) балл соответственно. Средняя продолжительность антикоагулянтной терапии до операции составила 4,2±1,9 года. Варфарин до операции принимали 38 (38%) пациентов, новые оральные антикоагулянты – остальные участники исследования. Интраоперационно полнота закрытия УЛП подтверждена чреспищеводной эхокардиографией. Средняя длина линии скоб составила 48 (35–75) мм. Однократно ампутация УЛП выполнена эндостеплером с длиной скоб 60 мм. 12 (12%) пациентам вследствие недостатка длины скоб УЛП удалено с помощью двух скоб длиной 45 мм. Ни у одного из больных не выявлено разрыва, прорезывания по линии скоб или разрывов окружающих эпикардиальных тканей. Антикоагулянтную терапию через 6 мес. после ТА отменили 70 (70%) пациентам с регистрацией устойчивого синусового ритма на 24-часовом холтеровском мониторировании электрокардиограммы, удовлетворительными результатами тестирования по шкале CHA2DS2-VASc и подтверждением отсутствия тромбов в левом предсердии по данным чреспищеводной эхокардиографии и мультиспиральной компьютерной томографии с контрастированием. Инсульты и транзиторные ишемические атаки в течение 1,2±0,7 года после отмены антикоагулянтной терапии не зарегистрированы.Заключение. Ампутация УЛП с использованием режуще-сшивающего эндостеплера с механизированной системой при ТА ФП является высокоэффективным и безопасным методом лечения пациентов с неклапанной ФП по сравнению с альтернативными методами исключения УЛП из системного кровотока

Replication Study and Meta-Analysis in European Samples Supports Association of the 3p21.1 Locus with Bipolar Disorder

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Genome-wide Association Study of Borderline Personality Disorder Reveals Genetic Overlap with Bipolar Disorder, Major Depression and Schizophrenia

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case–control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10−7) and PKP4 (P=8.67 × 10−7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10−3]), SCZ (rg=0.34 [P=4.37 × 10−5]) and MDD (rg=0.57 [P=1.04 × 10−3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Gene set enrichment analysis and expression pattern exploration implicate an involvement of neurodevelopmental processes in bipolar disorder

Bipolar disorder (BD) is a common and highly heritable disorder of mood. Genome-wide association studies (GWAS) have identified several independent susceptibility loci. In order to extract more biological information from GWAS data, multi-locus approaches represent powerful tools since they utilize knowledge about biological processes to integrate functional sets of genes at strongly to moderately associated loci.We conducted gene set enrichment analyses (GSEA) using 2.3 million single-nucleotide polymorphisms, 397 Reactome pathways and 24,025 patients with BD and controls. RNA expression of implicated individual genes and gene sets were examined in post-mortem brains across lifespan.Two pathways showed a significant enrichment after correction for multiple comparisons in the GSEA: GRB2 events in ERBB2 signaling, for which 6 of 21 genes were BD associated (PFDR = 0.0377), and NCAM signaling for neurite out-growth, for which 11 out of 62 genes were BD associated (PFDR = 0.0451). Most pathway genes showed peaks of RNA co-expression during fetal development and infancy and mapped to neocortical areas and parts of the limbic system.Pathway associations were technically reproduced by two methods, although they were not formally replicated in independent samples. Gene expression was explored in controls but not in patients.Pathway analysis in large GWAS data of BD and follow-up of gene expression patterns in healthy brains provide support for an involvement of neurodevelopmental processes in the etiology of this neuropsychiatric disease. Future studies are required to further evaluate the relevance of the implicated genes on pathway functioning and clinical aspects of BD

Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions

Parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. Once intracellular, Leishmania parasites must evade or deactivate the host's innate and adaptive immune responses in order to survive and replicate. We performed transcriptome profiling using RNA-seq to simultaneously identify global changes in murine macrophage and L. major gene expression as the parasite entered and persisted within murine macrophages during the first 72 h of an infection. Differential gene expression, pathway, and gene ontology analyses enabled us to identify modulations in host and parasite responses during an infection. The most substantial and dynamic gene expression responses by both macrophage and parasite were observed during early infection. Murine genes related to both pro- and anti-inflammatory immune responses and glycolysis were substantially upregulated and genes related to lipid metabolism, biogenesis, and Fc gamma receptor-mediated phagocytosis were downregulated. Upregulated parasite genes included those aimed at mitigating the effects of an oxidative response by the host immune system while downregulated genes were related to translation, cell signaling, fatty acid biosynthesis, and flagellum structure. The gene expression patterns identified in this work yield signatures that characterize multiple developmental stages of L. major parasites and the coordinated response of Leishmania-infected macrophages in the real-time setting of a dual biological system. This comprehensive dataset offers a clearer and more sensitive picture of the interplay between host and parasite during intracellular infection, providing additional insights into how pathogens are able to evade host defenses and modulate the biological functions of the cell in order to survive in the mammalian environment.https://doi.org/10.1186/s12864-015-2237-

TYPES OF COMPOSITION AND MODERN GARDEN PARK

The article describes the use of landscape compositions by species and their biomorphological appearance in the construction of modern gardens in the form of landscape design, as well as data on building indicators, area and appearance of Singaporean gardens with an innovative look

Assessment of the contribution of CFH and chromosome 10q26 AMD susceptibility loci in a Russian population isolate

Background/aims: A strong association has been confirmed between age-related macular degeneration (AMD) and variants at two independent loci including Tyr402His in the complement factor H (CFH) on 1q32 and Ser69Ala at LOC387715, a hypothetical gene on chromosome 10q26. The contribution of both loci to AMD was investigated in an isolated north-west Russian population. Methods: Together with a PLEKHA1 variant at 10q26, the CFH Tyr402His and LOC387715 Ser69Ala polymorphisms were genotyped in 155 patients with AMD and 151 age-matched controls. χ2 and Mantel–Haenszel (M–H) score tests were used to test for association. Sex-adjusted ORs were calculated. Results: The frequency of the Tyr402His C allele was significantly higher in patients with AMD compared with controls (pM–H = 0.0035). The increased risk observed in patients homozygous for the C allele (ORHOM = 2.71, 95% CI 1.25 to 5.90) in this indigenous Russian population was considerably lower than that observed in previous western Caucasian populations. A significant increase in the frequency of the LOC387715 variant was observed in patients with late-stage AMD compared with controls (pM–H = 0.007), with a homozygous OR of 3.47 (95% CI 1.01 to 11.9), although this association was not seen with early-stage AMD. Conclusion: The CFH gene contributes to AMD in this Russian population, although the risk conferred is considerably lower in this population than that found in other Western populations. A contribution of LOC387715 to disease in this population is also likely to be of weak effect