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  • 1
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. 23 ( 2021-12-07), p. 1845-1855
    Abstract: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92] ; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1466401-X
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  • 2
    In: Journal of Modern Oncology, Consilium Medicum, Vol. 24, No. 1 ( 2022-04-30), p. 12-23
    Abstract: Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced. Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC. Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013). Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found. Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.
    Type of Medium: Online Resource
    ISSN: 1815-1442 , 1815-1434
    Language: Unknown
    Publisher: Consilium Medicum
    Publication Date: 2022
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  • 3
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-6-13)
    Abstract: Cardiac AL amyloidosis as a complication of multiple myeloma (MM) is a formidable life-threatening condition. The first-line therapy for both MM and systemic AL amyloidosis is proteasome inhibitors (PIs). Unfortunately, the use of PIs may lead to cardiovascular toxicity development, which requires specific cardio-oncology supervision. Case Report A 57-year-old woman was admitted to a university hospital with clinical manifestation of progressive chronic heart failure. The patient had hypertension and no history of diabetes mellitus, myocardial infarction (MI), stroke, and arrhythmias. After a series of laboratory and instrumental examination methods, MM complicated by cardiac AL amyloidosis was proved. Upon specific cardio-oncology examination (NT-proBNP 4,274 pg/ml), ECHO showed systolic dysfunction, motion abnormalities in LV basal and middle segments, and a typical depositional myocardium pattern (“luminescence”); cardiac MRI revealed restrictive cardiomyopathy and specific hyperenhancement of the ventricles and atria; 24-h ECG showed QS-pattern in leads V1–V3 and unstable ventricular tachycardia (VT) paroxysms. Cardio-oncology consultation showed baseline cardiovascular risk was very high (≥20%), and cardioprotective therapy [iACE/ARBs, beta-blockers (BB), statins] was administered. The patient underwent VCD (bortezomib; cyclophosphamide; dexamethasone) chemotherapy (CMT) program. By the time of publication, the patient had received four CMT courses with a positive oncohematological and cardiovascular effect. Conclusion In this clinical case, we described a complication of MM, which was rare according to the severity and manifestation with restrictive cardiomyopathy due to secondary cardiac amyloidosis. The case's features were difficulties in verifying the underlying disease and its own complication, and the complexity of patient management according to modern principles of cardio-oncology.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 4
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4941-4941
    Abstract: Introduction. Primary immune thrombocytopenia is a rare disease1. The incidence of ITP is not well estimated in Russia and worldwide. In adults it varies from 1,6 to 3,9/100 000 person-years2-3. The gender and age-associated results are discussed and differ in several investigations4-6. Study objectives: evaluation of the incidence of primary immune thrombocytopenia in adults in one region of Russia Patients and methods. The data source is the Registry of the patients with primary ITP in Russia. 272 adult patients: 77 males (28%) and 195 females (72%), age from 16 to 89 years (median 44 years) with ITP (ICD-10 code D69.3), newly diagnosed cases during the period from 12 Jan 2014 to 24 May 2016. Results. 221 (81%) cases were newly diagnosed in 12 regions of Russia in which registration was performed most actively - more than 5 cases for the duration of the study. But only one region was selected for the first evaluation of epidemiological characteristics because of the number of reasons. There is one hematological central clinic in this region in which diagnosis of ITP can be verified and patients with ITP are treated and monitored most properly. The early started and fully performed registration process can be regarded as covered most part of region population in this target region. 86 cases (27 male, 59 female) were registered in the target region. The gender-age distribution was following: male: age 〈 41 = 10 (37%), age 〈 41-60 = 7 (26%), age 〉 60 = 10 (37%); female: age 〈 29 = 10 (49%), age 〈 41-60 = 15 (25%), age 〉 60 = 15 (25%). The estimated incidence rate in the target region is shown in table 1. The estimated incidence rates in gender-age strata in the target region are demonstrated in table 2. Conclusion. Overall ITP incidence in one region of Russia is 3.20/100 000 person-years. It is compatible to the incidence in other European countries. Our data demonstrate the rise of incidence rate in males with age and its decrease with age in female population. Literature. 1) Rodeghiero F., Stasi R., Gernsheimer T., Michel M., Provan D., Arnold D.M., et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from international working group. Blood. 2009; 113(11): 2386--93. doi: 10.1182/blood-2008-07-162503. 2) Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol. 2010; 85(3): 174-180. 3) Moulis G, Palmaro A, Montastruc J-L, Godeau B, Lapeyre-Mestre M, Sailler L. Epidemiology of incident immune thrombocytopenia: a natiowide population-based study in France. Blood. 2014; 124(22): 3308-3315. 4) Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4: 2377-83 5) Schoonen WM, Kucera G, Coelson J, et al. Epidemiology of immune thrombocytopenic purpura in the General Practise Research Database. Br J Haematol 2009; 145(2): 235-244. 6) Lisukov I.A., Maschan A.A., Shamardina A.V., Chagorova T.V., Davydkin I.L., Sycheva T.M., et al. Immune thrombocytopenia: clinical manifestations and response to therapy. Intermediate analysis of data of the Russian register of patients with primary immune thrombocytopenia and review of literature. Oncogematologiya. 2013; 2: 61--9]. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    In: Biomedicines, MDPI AG, Vol. 9, No. 11 ( 2021-11-09), p. 1649-
    Abstract: The molecular chaperone GroEL is designed to promote protein folding and prevent aggregation. However, the interaction between GroEL and the prion protein, PrPC, could lead to pathogenic transformation of the latter to the aggregation-prone PrPSc form. Here, the molecular basis of the interactions in the GroEL–PrP complex is studied with cryo-EM and molecular dynamics approaches. The obtained cryo-EM structure shows PrP to be bound to several subunits of GroEL at the level of their apical domains. According to MD simulations, the disordered N-domain of PrP forms much more intermolecular contacts with GroEL. Upon binding to the GroEL, the N-domain of PrP begins to form short helices, while the C-domain of PrP exhibits a tendency to unfold its α2-helix. In the absence of the nucleotides in the system, these processes are manifested at the hundred nanoseconds to microsecond timescale.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2720867-9
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  • 6
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-09-14)
    Abstract: The GroEL–GroES chaperonin complex is a bacterial protein folding system, functioning in an ATP-dependent manner. Upon ATP binding and hydrolysis, it undergoes multiple stages linked to substrate protein binding, folding and release. Structural methods helped to reveal several conformational states and provide more information about the chaperonin functional cycle. Here, using cryo-EM we resolved two nucleotide-bound structures of the bullet-shaped GroEL–GroES 1 complex at 3.4 Å resolution. The main difference between them is the relative orientation of their apical domains. Both structures contain nucleotides in cis and trans GroEL rings; in contrast to previously reported bullet-shaped complexes where nucleotides were only present in the cis ring. Our results suggest that the bound nucleotides correspond to ADP, and that such a state appears at low ATP:ADP ratios.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
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  • 7
    In: Journal of Modern Oncology, Consilium Medicum, Vol. 23, No. 1 ( 2021-05-19), p. 61-67
    Abstract: Relevance. PIK3CA belongs to the top three most frequently mutated genes in breast cancer (BC), especially in estrogen receptor (ER) positive, HER2 negative BC subtype. With an approval of selective PI3K-alpha inhibitor, alpelisib, this alteration has become actionable in ER+HER2- tumors. The frequency and spectrum of PIK3CA alterations in various cohorts is affected by a number of factors, including the distribution of BC expression subtypes, histological types, patient age, and even ethnicity. Aim. Aim of the current study was to characterize the frequency and spectrum of PIK3CA alterations in Russian BC patients. Materials and methods. The analysis of PIK3CA exon 7, 9 and 20 mutations was performed in a cohort of Russian ER+HER2- BC patients by a combination of high-resolution melting analysis, allele-specific PCR, and digital droplet PCR. Results. PIK3CA lesions were identified in 62/206 (30%) patients. Noteworthy, 59/62 (95%) of the identified variants were represented by the three most common p.E542K, p.E545K, and p.H1047R substitutions. The analysis of clinical and morphological characteristics revealed the trends towards association of PIK3CA mutations with older age and more frequent metastatic lung involvement. Conclusion. The obtained data on the frequency and spectrum of PIK3CA somatic aberrations can be helpful when organizing molecular genetic testing of breast cancer patients and using PI3K inhibitors in Russian population.
    Type of Medium: Online Resource
    ISSN: 1815-1442 , 1815-1434
    Language: Unknown
    Publisher: Consilium Medicum
    Publication Date: 2021
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  • 8
    Online Resource
    Online Resource
    FSBI Russian State Library ; 2009
    In:  Bibliotekovedenie [Russian Journal of Library Science] , No. 6 ( 2009-12-02), p. 24-28
    In: Bibliotekovedenie [Russian Journal of Library Science], FSBI Russian State Library, , No. 6 ( 2009-12-02), p. 24-28
    Abstract: The chronological classification of issues of natural-science subjects based on the periodization of the natural sciences development is considered in the article. . Author shows that publications of natural science in classical, non-classical and post-classical periods reflect the features of natural sciences of corresponding time. The issues of non-classical and post-non-classical stages can also inherit features of the previous ages.
    Type of Medium: Online Resource
    ISSN: 2587-7372 , 0869-608X
    URL: Issue
    Language: Unknown
    Publisher: FSBI Russian State Library
    Publication Date: 2009
    detail.hit.zdb_id: 3024094-3
    SSG: 24,1
    SSG: 7,41
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  • 9
    In: Hereditary Cancer in Clinical Practice, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2021-12)
    Abstract: Many cancer patients undergo sophisticated laboratory testing, which requires proper interpretation and interaction between different specialists. Case presentation We describe a patient with an extensive family history of cancer, who was diagnosed with bilateral breast cancer and two lung cancer lumps by the age of 40 years. She submitted a lung cancer specimen to a genetic profiling service, which reported the presence of the EGFR mutation (a combination of G719S and L833V substitutions) and the TP53 с.322_327del (p.G108_F109del) mutation in the tumor tissue. Possible therapeutic options were discussed at a medical conference, where one of the discussants raised a concern that the identified TP53 mutation may not necessarily be somatic, but reflect the germ-line status of the gene. Review of clinical records and follow-up dialog with the patient revealed, that she previously provided her blood for DNA analysis in two laboratories. The first laboratory utilized a custom NGS assay and did not detect the TP53 mutation, instead pointed to a potential pathogenic significance of the MSH6 c.2633 T  〉  C (p.V878A) allele. The second laboratory revealed the TP53 с.322_327del (p.G108_F109del) allele but stated in the written report that it has an unknown pathogenic significance. To resolve the possible uncertainty regarding the role of the TP53 с.322_327del (p.G108_F109del) variant, we suggested that the patient invite her second cousin for genetic testing, as she was affected by neuroblastoma at the age of 3 years. This analysis revealed the presence of the same TP53 variant. Conclusion We provide point-by-point discussion, reviewing multiple laboratory mistakes and clinical misinterpretations occurred with this patient. This case report exemplifies the need to involve rigorous clinical expertise in the daily practice of medical laboratory facilities.
    Type of Medium: Online Resource
    ISSN: 1897-4287
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2233352-6
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  • 10
    In: Consilium Medicum, Consilium Medicum, Vol. 24, No. 2 ( 2022-02-15), p. 90-95
    Abstract: Aim. To illustrate capabilities of the computational brain мagnetic resonance imaging (MRI) analyses on a small vessel disease (SVD) sample. Materials and methods. Thirty-one patients underwent brain MRI in standard sequences. We used Lesion Segmentation Tool to assess white matter hyperintensities (WMH) volume and Computational Anatomy Toolbox to calculate cortical thickness. Both software plug-ins work within the Statistical Parametric Mapping 12 software for MATLAB. We also performed cognitive testing with the Montreal Cognitive Assessment test and tests to detect hippocampal and executive domain dysfunction. Results. Sixteen patients had mild vascular cognitive impairment. The Median Fazekas scale score was 2 and 2 points. The median intracranial volume fraction occupied by the WMH was 0.07%. It correlated with the executive domain performance but not with cortical thickness. Cortical thickness within several clusters of the prefrontal complex and temporal lobe correlated with performance in cognitive tests. Among the computed MRI markers of the SVD, the occipital lobe cortical thickness had an area under the curve of 70%, and among the cognitive tests, the cued recall measure had an area under the curve of 73.8% to detect mild cognitive impairment. Conclusion. The abovementioned metrics is a valuable tool to objectively estimate white and grey matter state in patients with small vessel disease. Performing those analyses helped to assess SVD properties in the sample further and register new correlations between MRI and cognitive markers.
    Type of Medium: Online Resource
    ISSN: 2542-2170 , 2075-1753
    Language: Unknown
    Publisher: Consilium Medicum
    Publication Date: 2022
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