Long-Term Safety and Effectiveness of Dimethyl Fumarate in Patients with Multiple Sclerosis Treated in Routine Medical Practice: Final Analysis of the ESTEEM Study.

Introduction: Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.

Real-World Safety and Effectiveness of Dimethyl Fumarate in Patients with MS: Results from the ESTEEM Phase 4 and PROCLAIM Phase 3 Studies with a Focus on Older Patients.

Introduction: Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50 years old, yet data on their response to disease-modifying therapies (DMTs) is limited. Dimethyl fumarate (DMF) is an oral DMT approved for treating relapsing MS. This analysis evaluated the safety, efficacy, and immunophenotype changes of DMF in patients ≥ 50 years compared with patients < 50 years.

Environmental competencies for healthcare management at a 2nd education level as a component of strategic management.

Objective: Aim: To present the results of the analysis of educational standards and curricula of the second educational level of training of specialists, who may be managers of healthcare, on the content of the environmental component as an element of strategic management.

Patients And Methods: Materials and Methods: Content analysis 24 educational standards of the Ministry of Education and Science of Ukraine of Ukraine for 6 fields of knowledge and 200 master's curricula from 87 institutions of higher education of Ukraine.

Conclusion: Conclusions: There is a distribution of basic leadership and management competencies both by types of these competencies and between specialties.

Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis.

Multiple Sclerosis (MS) has been reported to be associated with intestinal inflammation and gut dysbiosis. To elucidate the underlying biology of MS-linked gut inflammation, we investigated gut infiltration of immune cells during the development of spontaneous experimental autoimmune encephalomyelitis (EAE) in humanized transgenic (Tg) mice expressing HLA-DR2a and human T cell receptor (TCR) specific for myelin basic protein peptide (MBP87-99)/HLA-DR2a complexes. Strikingly, we noted the simultaneous development of EAE and colitis, suggesting a link between autoimmune diseases of the central nervous system (CNS) and intestinal inflammation.

RELATIONSHIPS BETWEEN THE SOURCE OF HEALTH INFORMATION AND THE BEHAVIOR OF MOTHERS OF CHILDREN UNDER 5 YEARS OLD: CROSS-SECTIONAL STUDY ANALYSIS.

Objective: The aim: Is to investigate relationships between trusted sources of health information and people's behavior, including their attitudes toward vaccination and their willingness to seek medical care.

Patients And Methods: Materials and methods: The responses of 4,354 mothers of children under 5 years of age from all regions of Ukraine, who participated in the Multi-Indicator Cluster Household Survey (MICS-2012) were analyzed. The respondents were divided into separate groups using two-step cluster analysis.

METHODS FOR COMMUNICATION PROCESSES ENHANCEMENT IN THE "PROVIDER-CONSUMER (LEARNER)" SYSTEM OF EDUCATIONAL SERVICES.

Objective: The aim: To determine learners' (doctors) needs and draw up proposals for upgrading educational communication processes in the "provider-consumer" system of educational services.

Patients And Methods: Materials and methods: The biblio-semantic, biostatistic and sociological methods were used. 754 author questionnaires were processed.

Fibrinolysis induced clinical improvement in a patient with multiple sclerosis exacerbation.

Background: Recently, extravascular fibrinogen leakage has emerged as a potential trigger of local neuroinflammation in the CNS. In the animal models of MS, fibrin depletion decreased neuroinflammation and neurodegeneration. The role of fibrinolytic therapy in patients with MS has not been studied.

Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis.

A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment.

Imaging of Central Nervous System Demyelinating Disorders.

Purpose Of Review: This article focuses on neuroimaging in multiple sclerosis (MS), the most common central nervous system (CNS) demyelinating disorder encountered by practicing neurologists. Less common adult demyelinating disorders and incidental subclinical white matter abnormalities that are often considered in the differential diagnosis of MS are also reviewed.

Recent Findings: Advancements in neuroimaging techniques, eg, the application of ultrahigh-field MRI, are rapidly expanding the use of neuroimaging in CNS demyelinating disorders.

Decreased Dicer expression is linked to increased expression of co-stimulatory molecule CD80 on B cells in multiple sclerosis.

Background: Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system. B cells have been strongly implicated in disease pathogenesis based on clinical trials with B-cell ablation. There is a growing body of evidence linking microRNAs with regulation of the immune system.

MMP-9 expression is increased in B lymphocytes during multiple sclerosis exacerbation and is regulated by microRNA-320a.

B cells are necessary to maintain disease activity in relapsing multiple sclerosis (MS) and produce matrix metallopeptidase-9 (MMP-9), which disrupts the blood-brain barrier. MMP-9 protein expression was increased and expression of microRNA-320a (miR-320a), which targets MMP-9 mRNA, was significantly decreased in B lymphocytes of MS patients during a disease relapse compared to remission. Functional significance of these findings was demonstrated by transfecting human B lymphocytes with miR-320a inhibitor, which led to increased MMP-9 expression and secretion.

Comparison of IFN-β inducible gene expression in primary-progressive and relapsing-remitting multiple sclerosis.

Interferon (IFN)-β is a type I IFN commonly produced by the innate immune system in response to viral infection. IFN-β is also used for the treatment of patients with the relapsing-remitting form of multiple sclerosis (RRMS); however, IFN-β therapy is unable to confer a significant benefit for primary-progressive MS (PPMS) patients. In this study, we assessed the gene profiles of peripheral blood mononuclear cells (PBMCs) isolated from PPMS, RRMS, and healthy donors (HD) in response to IFN-β treatment in vitro to examine genetic mechanisms underlying the inadequate response of IFN-β therapy in PPMS patients.

Plasmacytoid dendritic cells and immunotherapy in multiple sclerosis.

Plasmacytoid dendritic cells (pDCs) are specialized APCs implicated in the pathogenesis of many human diseases. Compared with other peripheral blood mononuclear cells, pDCs express a high level of TLR9, which recognizes viral DNA at the initial phase of viral infection. Upon stimulation, these cells produce large amounts of type I interferon and other proinflammatory cytokines and are able to prime T lymphocytes.

Acute demyelinating lesions with restricted diffusion in multiple sclerosis.

Background And Objectives: It is widely accepted that typical acute demyelinating lesions in relapsing-remitting multiple sclerosis (RRMS) exhibit vasogenic edema with increased diffusion, as demonstrated by an increased apparent diffusion coefficient on MRI. In contrast, acute ischemic lesions demonstrate cytotoxic edema with restricted diffusion. Recent reports have documented selected cases of acute demyelinating lesions exhibiting restricted diffusion (ADLRD) in MS.

Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse.

The plasmacytoid dendritic cells (pDCs) express a high level of Toll-like receptor 9 (TLR-9), which recognizes viral DNA. Activated via TLR-9, pDCs also secrete large amounts of type I interferon which are involved either in stimulation or down regulation of immune response in multiple sclerosis (MS). In the present study, we determinate pDCs levels by flow cytometry in Cerebrospinal Fluid (CSF) and Peripheral Blood from MS patients in relapsing and in remitting phases of the disease, comparing with other non-inflammatory diseases (OND).

Interferon-β inhibits toll-like receptor 9 processing in multiple sclerosis.

Objective: Viral infections have been implicated in the pathogenesis of multiple sclerosis (MS). Plasmacytoid dendritic cells (pDCs) are present in peripheral blood, cerebrospinal fluid, and brain lesions of MS patients. pDCs sense viral DNA via Toll-like receptor 9 (TLR9), which has to be cleaved from the N-terminal to become functional (TLR9 processing).

Seasonal prevalence of MS disease activity.

Objective: This observational cohort study investigated the seasonal prevalence of multiple sclerosis (MS) disease activity (likelihood and intensity), as reflected by new lesions from serial T2-weighted MRI, a sensitive marker of subclinical disease activity.

Methods: Disease activity was assessed from the appearance of new T2 lesions on 939 separate brain MRI examinations in 44 untreated patients with MS. Likelihood functions for MS disease activity were derived, accounting for the temporal uncertainty of new lesion occurrence, individual levels of disease activity, and uneven examination intervals.

Plasmacytoid dendritic cells in multiple sclerosis: chemokine and chemokine receptor modulation by interferon-beta.

Plasmacytoid dendritic cells (pDCs) are present in peripheral blood, leptomeninges and demyelinating lesions in patients with multiple sclerosis (MS). The ability of pDCs to produce chemokines and express the chemokine receptor CCR7 in MS is not known. We studied pDCs in MS patients and healthy subjects.

Optic neuritis incidence is increased in spring months in patients with asymptomatic demyelinating lesions.

Optic neuritis (ON) patients can be divided into two groups based on the presence or absence of asymptomatic demyelinating lesions (ADLs) on brain MRI. The presence of ADLs is associated with an increased risk of progression to clinically definite multiple sclerosis (CDMS). The clinical data and brain MRI of 110 patients with acute unilateral ON were analyzed.

Acute multiple sclerosis lesion: conversion of restricted diffusion due to vasogenic edema.

It is widely accepted that acute demyelinating plaques in patients with multiple sclerosis (MS) demonstrate increased apparent diffusion coefficient (ADC) and increased diffusion weighted imaging (DWI) signals on MRI. These imaging characteristics in acute MS lesions have been postulated to be due to peripheral vasogenic edema that typically increases the ADC. This assumption is commonly used to differentiate stroke from MS lesions since acute and subacute stroke lesions demonstrate increased DWI signal with reduced ADC due to acute cytotoxic edema.

Percent predicted value for the 6-minute walk test: using norm-referenced equations to characterize severity in persons with CHF.

Background: The 6-minute walk test (6MWT) is a widely used measure of functional capacity in patients with chronic heart failure (CHF). Norm-referenced equations that predict the 6-minute walk distance (6MWD) according to age, height, weight, and gender have been proposed for healthy patients. We explored whether these equations apply to CHF patients.

IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production.

IL-23 is a heterodimeric cytokine comprising a p19 subunit associated with the IL-12/23p40 subunit. Like IL-12, IL-23 is expressed predominantly by activated dendritic cells (DCs) and phagocytic cells, and both cytokines induce IFN-gamma secretion by T cells. The induction of experimental autoimmune encephalitis, the animal model of multiple sclerosis (MS), occurs in mice lacking IL-12, but not in mice with targeted disruption of IL-23 or both IL-12 and IL-23.

Cyclophosphamide modulates CD4+ T cells into a T helper type 2 phenotype and reverses increased IFN-gamma production of CD8+ T cells in secondary progressive multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system considered to be mediated by T helper type-1 cells. Several agents have been found to modify the disease course of MS, including interferon-beta1 (IFN-beta1), glatiramer acetate mitoxantrone. We have employed pulse therapy with cyclophosphamide in a selected group of patients with actively progressive disease.