Role of oral teriflunomide in the management of multiple sclerosis

The landscape of the treatment of relapsing–remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing–remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing–remitting multiple sclerosis is discussed

Do Antiretroviral Drugs Protect From Multiple Sclerosis by Inhibiting Expression of MS-Associated Retrovirus?

The expression of human endogenous retroviruses (HERVs) has been associated with Multiple Sclerosis (MS). The MS-related retrovirus (MSRV/HERV-W) has the potential to activate inflammatory immunity, which could promote both susceptibility and progression toward MS. A connection between HERVs and MS is also supported by the observation that people infected with the human immunodeficiency virus (HIV) may have a lower risk of developing MS than the HIV non-infected, healthy population. This may be due to suppression of HERV expression by antiretroviral therapies (ART) used to treat HIV infection. In this pilot study, we compared RNA expression of the envelope gene of MSRV/HERV-W, as well as Toll-like receptors (TLR) 2 and 4, in a small cohort of HIV+ patients with MS patients and healthy controls (HC). An increased expression of MSRV/HERV-Wenv and TLR2 RNA was detected in blood of MS patients compared with HIV patients and HC, while TLR4 was increased in both MS and HIV patients. There was, however, no difference in MSRV/HERV-Wenv, TLR2 and TLR4 expression between ART-treated and -untreated HIV patients. The viral protein Env was expressed mainly by B cells and monocytes, but not by T cells and EBV infection could induce the expression of MSRV/HERV-Wenv in Lymphoblastoid cell lines (LCLs). LCLs were therefore used as an in vitro system to test the efficacy of ART in inhibiting the expression of MSRV/HERV-Wenv. Efavirenz (a non-nucleoside reverse transcriptase inhibitor) alone or different combined drugs could reduce MSRV/HERV-Wenv expression in vitro. Further, experiments are needed to clarify the potential role of ART in protection from MS

Actuación en el quirófano ante la pandemia de la enfermedad por Coronavirus-19.

[Resumen] El 11 de marzo de 2020, la Organización Mundial de la Salud (OMS) declaró una pandemia global debido a la enfermedad por coronavirus-19 (COVID-19). Esta pandemia trajo una cancelación a nivel global de las cirugías electivas. Teniendo en cuenta que la atención quirúrgica es un componente clave de cualquier sistema de salud, cuando la situación sanitaria mejoró se fueron reintroduciendo poco a poco las cirugías electivas. El objetivo de esta revisión narrativa fue analizar las distintas recomendaciones y protocolos de actuación en quirófano frente a la pandemia de la COVID-19, para poder preservar tanto la seguridad de los pacientes como la de los sanitarios, y así poder reintroducir las cirugías electivas. Metodología. Se llevó a cabo una estrategia de búsqueda bibliográfica usando distintos descriptores de ciencias de la Salud (DeCS) en las principales bases de datos (BBSS) como PubMed, Dialnet, SciELO y Google Académico, incluyéndose artículos procedentes de revistas indexadas en el Journal Citation Report (JCR). También se analizaron protocolos publicados por distintas instituciones tanto sanitarias como gubernamentales. Conclusión. Gracias al análisis de distintos parámetros, que ayudan a definir en qué nivel de emergencia se encuentra una zona sanitaria, se crearon pautas de conducta y protocolos que sirven de guía para la reintroducción de las cirugías electivas. Esta reintroducción es posible gracias a la priorización de los casos que se deben operar, la adaptación de las distintas recomendaciones elaboradas y la optimización de los recursos existentes.[Resumo] O 11 de marzo de 2020, a Organización Mundial da Saúde (OMS) declarou unha pandemia global debido á enfermidade por coronavirus-19 (COVID-19). Esta pandemia trouxo unha cancelación a nivel global das cirurxías electivas. Tendo en conta que a atención cirúrxica é un compoñente clave de calquera sistema de saúde, cando a situación sanitaria mellorou reintroducíronse progresivamente as cirurxías electivas. O obxectivo desta revisión narrativa foi analizar as distintas recomendacións e protocolos de actuación en quirófano fronte á pandemia da COVID-19, para poder preservar tanto a seguridade dos pacientes como a dos sanitarios, e así poder reintroducir as cirurxías electivas. Metodoloxía. Levouse a cabo unha estratexia de procura bibliográfica usando distintos descritores de ciencias da Saúde (DeCS) nas principais bases de datos (BBSS) como PubMed, Dialnet, SciELO e Google Académido, incluíndose artigos procedentes de revistas indexadas no Journal Citation Report (JCR). Tamén se analizaron protocolos publicados por distintas institucións tanto sanitarias como gobernamentais. Conclusión. Grazas á análise de distintos parámetros, que axudan a definir en que nivel de emerxencia se atopa unha zona sanitaria, creáronse pautas de conduta e protocolos que serven de guía para a reintrodución das cirurxías electivas. Esta reintrodución é posible grazas á priorización dos casos que se deben operar, a adaptación das distintas recomendacións elaboradas e a optimización dos recursos existentes.[Abstract] On 11 March 2020, the World Health Organization (WHO) declared a global pandemic due to coronavirus disease-19 (COVID-19). This pandemic brought a global cancellation of elective surgeries. Considering that surgical care is a key component of any health system, as the health situation improved, elective surgeries were gradually reintroduced. The aim of this narrative review was to analyse the different recommendations and protocols for operating room management in the face of the COVID-19 pandemic, in order to preserve both patient and healthcare professionals safety, and to reintroduce elective surgeries. Methodology. A bibliographic search strategy was carried out using different Medical Subject Heading (MeSH) in the main databases such as PubMed, Dialnet, SciELO and Google Scholar, including articles from journals indexed in the Journal Citation Report (JCR). Protocols published by different health and governmental institutions were also analysed. Conclusion. Thanks to the analysis of different parameters, which help to define the level of emergency in a health area, guidelines and protocols were created to guide the reintroduction of elective surgery. This reintroduction is possible thanks to the prioritisation of the cases to be operated on, the adaptation of the different recommendations developed and the optimisation of existing resources.Traballo fin de grao (UDC.FEP). Enfermaría. Curso 2020/202

Ocrelizumab B cell depletion has no effect on HERV RNA expression in PBMC in MS patients

Background: Epstein barr virus (EBV) infection of B cells is now understood to be one of the triggering events for the development of Multiple Sclerosis (MS), a progressive immune-mediated disease of the central nervous system. EBV infection is also linked to expression of human endogenous retroviruses (HERVs) of the HERV-W group, a further risk factor for the development of MS. Ocrelizumab is a high-potency disease-modifying treatment (DMT) for MS, which depletes B cells by targeting CD20. Objectives: We studied the effects of ocrelizumab on gene expression in peripheral blood mononuclear cells (PBMC) from paired samples from 20 patients taken prior to and 6 months after beginning ocrelizumab therapy. We hypothesised that EBV and HERV-W loads would be lower in post-treatment samples.Methods: Samples were collected in Paxgene tubes, subject to RNA extraction and Illumina paired end short read mRNA sequencing with mapping of sequence reads to the human genome using Salmon and differential gene expression compared with DeSeq2. Mapping was also performed separately to the HERV-D database of HERV sequences and the EBV reference sequence.Results: Patient samples were more strongly clustered by individual rather than disease type (relapsing/remitting or primary progressive), treatment (pre and post), age, or sex. Fourteen genes, all clearly linked to B cell function were significantly down regulated in the post treatment samples. Interestingly only one pre-treatment sample had detectable EBV RNA and there were no significant differences in HERV expression (of any group) between pre- and post-treatment samples.Conclusions: While EBV and HERV expression are clearly linked to triggering MS pathogenesis, it does not appear that high level expression of these viruses is a part of the ongoing disease process or that changes in virus load are associated with ocrelizumab treatment

Smoking cessation and the reduction of disability progression in Multiple Sclerosis: a cohort study

Background: Smoking is associated with a more severe disease course in people with multiple sclerosis (MS). The magnitude of effect of smoking cessation on MS progression is unknown. The aim of this study was to quantify the impact of smoking cessation on reaching MS disability milestones. Methods: This is a cross-sectional study with retrospective reports. A comprehensive smoking questionnaire was sent to 1270 patients with MS registered between 1994 and 2013 in the Nottingham University Hospital MS Clinics database. Demographic and clinical data were extracted from the clinical database. Cox proportional hazard regression was used to estimate effects of smoke-free years on the time to Expanded Disability Status Scale (EDSS) scores 4.0 and 6.0. MS Impact Scale 29 (MSIS-29) and Patient Determined Disease Steps (PDDS) were used to assess the physical and psychological impact of smoking. Results: Each ‘smoke-free year’ was associated with 0.96 (95% CI: 0.95 to 0.97) times decreased risk of reaching EDSS 4.0 and 0.97 (95%CI: 0.95 to 0.98) times decreased risk of reaching EDSS 6.0. Non-smokers showed a significantly lower level of disability in all the self-reported outcomes compared with current smokers. Conclusion: The reduction in the risk of disability progression after smoking cessation is significant and time-dependent. The earlier the patients quit, the stronger the reduction in the risk of reaching disability milestones. The quantitative estimates of the impact of smoking cessation on reaching disability milestones in MS can be used in interventional trials

Modern therapeutic options in diabetic foot ulcer

Diabetic foot is a severe complication of diabetes that occurs as a result of poor glycemic control, being associated with significant morbidity and mortality. Mortality associated with this disease is estimated at 5% in the first 12 months, and about 42% in the next 5 years. On average, it affects about 15% of people with diabetes during their lifetime, including as possible manifestations neuropathy, peripheral vascular disease, and subsequent ulceration which, if treated incorrectly, can lead to amputation. This paper presents a retrospective and descriptive study of patients diagnosed and treated for diabetic foot ulcers in the Proctoven Clinic. The study includes a group of 50 cases diagnosed with diabetic foot over a period of 5 years, from 01.01.2017 to 31.12.2021. In this study, the effectiveness of the modern treatment methods most frequently used in the surgical treatment of the diabetic foot is analyzed based on several parameters

Coordinate based random effect size meta-analysis of neuroimaging studies

Low power in neuroimaging studies can make them difficult to interpret, and Coordinate based meta-analysis (CBMA) may go some way to mitigating this issue. CBMA has been used in many analyses to detect where published functional MRI or voxel-based morphometry studies testing similar hypotheses report significant summary results (coordinates) consistently. Only the reported coordinates and possibly t statistics are analysed, and statistical significance of clusters is determined by coordinate density. Here a method of performing coordinate based random effect size meta-analysis and meta-regression is introduced. The algorithm (ClusterZ) analyses both coordinates and reported t statistic or Z score, standardised by the number of subjects. Statistical significance is determined not by coordinate density, but by a random effects meta-analyses of reported effects performed cluster-wise using standard statistical methods and taking account of censoring inherent in the published summary results. Type 1 error control is achieved using the false cluster discovery rate (FCDR), which is based on the false discovery rate. This controls both the family wise error rate under the null hypothesis that coordinates are randomly drawn from a standard stereotaxic space, and the proportion of significant clusters that are expected under the null. Such control is necessary to avoid propagating and even amplifying the very issues motivating the meta-analysis in the first place. ClusterZ is demonstrated on both numerically simulated data and on real data from reports of grey matter loss in multiple sclerosis (MS) and syndromes suggestive of MS, and of painful stimulus in healthy controls. The software implementation is available to download and use freely