Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19

Introduction: Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. Patients and methods: We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. Results: Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28–54) vs 45 (28–56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28–79) vs 68 (30–125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19–62) vs 53 (20–92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. Discussion and conclusions: Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment.</p

Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries

Background: Adenovirus-based COVID-19 vaccines are extensively used in low- and middle-income countries (LMICs). Remarkably, cases of cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) have rarely been reported from LMICs. Aims: We studied the frequency, manifestations, treatment, and outcomes of CVST-VITT in LMICs. Methods: We report data from an international registry on CVST after COVID-19 vaccination. VITT was classified according to the Pavord criteria. We compared CVST-VITT cases from LMICs to cases from high-income countries (HICs). Results: Until August 2022, 228 CVST cases were reported, of which 63 were from LMICs (all middle-income countries [MICs]: Brazil, China, India, Iran, Mexico, Pakistan, Turkey). Of these 63, 32 (51%) met the VITT criteria, compared to 103 of 165 (62%) from HICs. Only 5 of the 32 (16%) CVST-VITT cases from MICs had definite VITT, mostly because anti-platelet factor 4 antibodies were often not tested. The median age was 26 (interquartile range [IQR] 20–37) versus 47 (IQR 32–58) years, and the proportion of women was 25 of 32 (78%) versus 77 of 103 (75%) in MICs versus HICs, respectively. Patients from MICs were diagnosed later than patients from HICs (1/32 [3%] vs. 65/103 [63%] diagnosed before May 2021). Clinical manifestations, including intracranial hemorrhage, were largely similar as was intravenous immunoglobulin use. In-hospital mortality was lower in MICs (7/31 [23%, 95% confidence interval (CI) 11–40]) than in HICs (44/102 [43%, 95% CI 34–53], p = 0.039). Conclusions: The number of CVST-VITT cases reported from LMICs was small despite the widespread use of adenoviral vaccines. Clinical manifestations and treatment of CVST-VITT cases were largely similar in MICs and HICs, while mortality was lower in patients from MICs.</p

Effect of the Sera of Patients with Multiple Sclerosis on Apoptosis and Nitric Oxide Production of Endothelial Cells

Abstract: Background & Aims: Multiple sclerosis (MS) is one of the chronic autoimmune diseases of the central nervous system with unknown etiology. The present study aimed to investigate the apoptosis and nitric oxide (NO) production of endothelial cells treated with serum of patients with MS and response to interferon beta (IFN-?) therapy. Methods: Human umbilical vein endothelial cells were treated with sera from patients with active MS (in relapse), MS in remission, or sera from healthy volunteers (each n = 10). Nitric oxide (NO) levels were determined in culture supernatants by Greiss method and endothelial cell apoptosis was assessed by annexin V-propidium iodide staining. Effects of IFN-beta-1b on endothelial cell apoptosis and NO production were tested at increasing doses (10, 100, and 1000 U/ml). Results: Compared with healthy people, only apoptosis of endothelial cells treated with serum of patients with relapsing phase increased, P<0.01; while there was no significant difference between apoptosis of endothelial cells treated with serum of patients in remission phase and healthy controls. Apoptosis of endothelial cells treated with sera of patients in relapse was decreased by IFN-beta-1b at 10 U/ml, P<0.05. The same dose also led to a significant increase in nitric oxide production. Conclusion: The results suggest that endothelial cells injury and apoptosis may play a role in MS etiology and represents a potential therapeutic mechanism of action for IFN-beta-1b in MS therapy. Keywords: Multiple sclerosis, Interferon beta-1b (IFN-beta-1b), Endothelial cell apoptosis, Nitric oxid

The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility.

Multiple sclerosis (MS) is the most common neurological disease of the central nervous system affecting young adults. While the etiology of the disease is still unknown, epidemiological and genetics studies have shown a significant inherited component involved in MS pathogenesis. Single nucleotide polymorphisms (SNPs) associated with MS have been recently evaluated by two main groups of high-throughput genotyping analyses: candidate gene approaches and genome-wide association studies (GWAS). Although both types of studies have identified polymorphisms in the human leukocyte antigen (HLA) region as the strongest susceptibility loci for MS, recent investigations have identified a broad spectrum of non-HLA genes prominently associated with MS. This review will focus on recent findings in non-HLA genes as well as their SNPs which have shown high linkage to MS as a genetic-based disorder. Understanding of non-HLA polymorphisms will help elucidate the signalling aberrations involved in MS development and may help to identify novel, personalized approaches to therapy

Analysis of nonlinear oscillations of a punctual charge in the electric field of a charged ring via a Hamiltonian approach and the energy balance method

WOS: 000292853300047The method of Hamiltonian approach and the energy balance method are applied to obtain the periodic solutions of nonlinear oscillations of a punctual charge in the electric field of charged ring. The obtained approximate frequencies are accurate for the entire range of oscillation amplitudes. A good agreement of the approximate frequencies and periodic solutions with the exact ones are demonstrated and discussed. It is also proved that the results of the energy balance method are better than the Hamiltonian approach for solving this equation.(C) 2011 Elsevier Ltd. All rights reserved

Higher order approximate periodic solutions for nonlinear oscillators with the Hamiltonian approach

WOS: 000294886000015In this work, the Hamiltonian approach is applied to obtain the natural frequency of the Duffing oscillator, the nonlinear oscillator with discontinuity and the quintic nonlinear oscillator. The Hamiltonian approach is then extended to the second and third orders to find more precise results. The accuracy of the results obtained is examined through time histories and error analyses for different values for the initial conditions. Excellent agreement of the approximate frequencies and the exact solution is demonstrated. It is shown that this method is powerful and accurate for solving nonlinear conservative oscillatory systems. (C) 2011 Elsevier Ltd. All rights reserved