I.M. Sechenov First Moscow State Medical University

About: I.M. Sechenov First Moscow State Medical University is a education organization based out in Moscow, Russia. It is known for research contribution in the topics: Medicine & Population. The organization has 7984 authors who have published 9355 publications receiving 68997 citations.

ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment.

Abstract: Poststroke cognitive impairment is a debilitating consequence of stroke. The aim of this study was to assess whether Actovegin confers cognitive benefit in patients who have had an ischemic stroke.This was a 12-month, parallel-group, randomized, multicenter, double-blind, placebo-controlled study. Eligible patients were ≥60 years of age with a Montreal Cognitive Assessment test score of ≤25 points. Patients were randomized into 2 groups within 1 week of acute supratentorial ischemic stroke in a 1:1 ratio: Actovegin (a deproteinized hemoderivative of calf blood, 2000 mg/d for ≤20 intravenous infusions followed by 1200 mg/d orally) or placebo for 6 months. Patients were treated in accordance with standard clinical practice for a further 6 months. The primary end point was the change from baseline in Alzheimer's Disease Assessment Scale, cognitive subscale, extended version at 6 months.Two-hundred forty-eight patients were randomized to Actovegin and 255 patients to placebo. At month 6, the least squares mean change from baseline in Alzheimer's Disease Assessment Scale, cognitive subscale, extended version was -6.8 for Actovegin and -4.6 for placebo; the estimated treatment difference was -2.3 (95% confidence interval, -3.9, -0.7; P=0.005). Recurrent ischemic stroke was the most frequently reported serious adverse event, with a nonsignificantly higher number for Actovegin versus placebo.Actovegin had a beneficial effect on cognitive outcomes in patients with poststroke cognitive impairment. The safety experience was consistent with the known safety and tolerability profile of the drug. These results warrant confirmation in additional robustly designed studies.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01582854.

The PPAR pan-agonist bezafibrate ameliorates cardiomyopathy in a mouse model of Barth syndrome.

Abstract: The PGC-1α/PPAR axis has been proposed as a potential therapeutic target for several metabolic disorders. The aim was to evaluate the efficacy of the pan-PPAR agonist, bezafibrate, in tafazzin knockdown mice (TazKD), a mouse model of Barth syndrome that exhibits age-dependent dilated cardiomyopathy with left ventricular (LV) dysfunction. The effect of bezafibrate on cardiac function was evaluated by echocardiography in TazKD mice with or without beta-adrenergic stress. Adrenergic stress by chronic isoproterenol infusion exacerbates the cardiac phenotype in TazKD mice, significantly depressing LV systolic function by 4.5 months of age. Bezafibrate intake over 2 months substantially ameliorates the development of LV systolic dysfunction in isoproterenol-stressed TazKD mice. Without beta-adrenergic stress, TazKD mice develop dilated cardiomyopathy by 7 months of age. Prolonged treatment with suprapharmacological dose of bezafibrate (0.5% in rodent diet) over a 4-month period effectively prevented LV dilation in mice isoproterenol treatment. Bezafibrate increased mitochondrial biogenesis, however also promoted oxidative stress in cardiomyocytes. Surprisingly, improvement of systolic function in bezafibrate-treated mice was accompanied with simultaneous reduction of cardiolipin content and increase of monolysocardiolipin levels in cardiac muscle. Thus, we demonstrate that bezafibrate has a potent therapeutic effect on preventing cardiac dysfunction in a mouse model of Barth syndrome with obvious implications for treating the human disease. Additional studies are needed to assess the potential benefits of PPAR agonists in humans with Barth syndrome.

Low prevalence of bronchial asthma and chronic obstructive lung disease among intensive care unit patients with COVID-19.

Abstract: R E FE R E N C E S 1. Confino-Cohen R, Rosman Y, Lachover I, Meir Shafrir K, Goldberg A. The importance of amoxicillin and amoxicillin-clavulanate determinants in the diagnosis of immediate allergic reactions to beta-lactams. Int Arch Allergy Immunol. 2016;170(1):62-66. 2. ACSQHC AURA 2017. Second Australian report on antimicrobial use and resistance in human health 2017 [cited 2019 24/3/2019]: ht tps://w w w.safet yandq ual i t y.gov.au/wp-conte nt/uploa ds/2018/01/AURA-2017-Secon d-Austr alian -repor t-on-Antim icrob ial-Use-and-Resis tance -in-human -health.pdf 3. Silveira AM, Gaspar Â, Benito-Garcia F, et al. Anaphylaxis to clavulanic acid: a 7-year survey. J Investig Allergol Clin Immunol. 2019;29(4):311-313. 4. Trubiano JA, Thursky KA, Stewardson AJ, et al. impact of an integrated antibiotic allergy testing program on antimicrobial stewardship: a multicenter evaluation. Clin Infect Dis. 2017;65(1):166-174. 5. Romano A, Blanca M, Torres MJ, et al. Diagnosis of nonimmediate reactions to beta-lactam antibiotics. Allergy. 2004;59(11):1153-1160. 6. Trubiano JA, Strautins K, Redwood AJ, et al. The combined utility of Ex vivo IFN-gamma release enzyme-linked immunospot assay and in vivo skin testing in patients with antibiotic-associated severe cutaneous adverse reactions. J Allergy Clin Immunol Pract. 2018;6(4):1287-1296 e1. 7. Keane NM, Roberts SG, Almeida CA, et al. High-avidity, high-IFNgamma-producing CD8 T-cell responses following immune selection during HIV-1 infection. Immunol Cell Biol. 2012;90(2):224-234. 8. Trubiano JA, Gordon CL, Castellucci C, et al. Analysis of skin-resident memory t cells following drug hypersensitivity reactions. J Invest Dermatol. 2019. 9. Lezmi G, Alrowaishdi F, Bados-Albiero A, et al. Non-immediatereading skin tests and prolonged challenges in non-immediate hypersensitivity to beta-lactams in children. Pediatr Allergy Immunol. 2018;29(1):84-89. 10. Meng J, Thursfield D, Lukawska JJ. Allergy test outcomes in patients self-reported as having penicillin allergy: Two-year experience. Ann Allergy Asthma Immunol. 2016;117(3):273-279. 11. Bonadonna P, Schiappoli M, Senna G, Passalacqua G. Delayed selective reaction to clavulanic acid: a case report. J Investig Allergol Clin Immunol. 2005;15(4):302-304. 12. Amaral L, Carneiro-Leao L, Cernadas JR. Acute generalized exanthematous pustulosis due to clavulanic acid. J Allergy Clin Immunol Pract. 2019;8(3):1083-1084. 13. Torres MJ, Ariza A, Mayorga C, et al. Clavulanic acid can be the component in amoxicillin-clavulanic acid responsible for immediate hypersensitivity reactions. J Allergy Clin Immunol. 2010;125(2):502505 e2. 14. Sanchez-Morillas L, Pérez-Ezquerra PR, Reaño-Martos M, LagunaMartínez JJ, Sanz ML, Martínez LM. Selective allergic reactions to clavulanic acid: a report of 9 cases. J Allergy Clin Immunol. 2010;126(1):177-179. 15. Salas M, Laguna JJ, Doña I, et al. Patients taking amoxicillin-clavulanic can become simultaneously sensitized to both drugs. J Allergy Clin Immunol Pract. 2017;5(3):694-702 e3. 16. Fernandez J, Torres MJ, Campos J, Arribas-Poves F, Blanca M, Group DA-D. Prospective, multicenter clinical trial to validate new products for skin tests in the diagnosis of allergy to penicillin. J Investig Allergol Clin Immunol. 2013;23(6):398-408.

Endothelial to mesenchymal transition contributes to arsenic-trioxide-induced cardiac fibrosis.

Abstract: Emerging evidence has suggested the critical role of endothelial to mesenchymal transition (EndMT) in fibrotic diseases. The present study was designed to examine whether EndMT is involved in arsenic trioxide (As2O3)-induced cardiac fibrosis and to explore the underlying mechanisms. Cardiac dysfunction was observed in rats after exposure to As2O3 for 15 days using echocardiography and the deposition of collagen was detected by Masson’s trichrome staining and electron microscope. EndMT was indicated by the loss of endothelial cell markers (VE-cadherin and CD31) and the acquisition of mesenchymal cell markers (α-SMA and FSP1) determined by RT-PCR at the mRNA level and Western blot and immunofluorescence analysis at the protein level. In the in-vitro experiments, endothelial cells acquired a spindle-shaped morphology accompanying downregulation of the endothelial cell markers and upregulation of the mesenchymal cell markers when exposed to As2O3. As2O3 activated the AKT/GSK-3β/Snail signaling pathway and blocking this pathway with PI3K inhibitor (LY294002) abolished EndMT in As2O3-treated endothelial cells. Our results highlight that As2O3 is an EndMT-promoting factor during cardiac fibrosis, suggesting that targeting EndMT is beneficial for preventing As2O3-induced cardiac toxicity.