Novel Surfaces in Extracorporeal Membrane Oxygenation Circuits

The balance between systemic anticoagulation and clotting is challenging. In normal hemostasis, the endothelium regulates the balance between anticoagulant and prothrombotic systems. It becomes particularly more challenging to maintain this physiologic hemostasis when we are faced with extracorporeal life support therapies, where blood is continuously in contact with a foreign extracorporeal circuit surface predisposing a prothrombotic state. The blood-surface interaction during extracorporeal life support therapies requires the use of systemic anticoagulation to decrease the risk of clotting. Unfractionated heparin is the most common anticoagulant agent widely used in this setting. New trends include the use of direct thrombin inhibitor agents for systemic anticoagulation; and surface modifications that aim to overcome the blood-biomaterial surface interaction by modifying the hydrophilicity or hydrophobicity of the polymer surface; and coating the circuit with substances that will mimic the endothelium or anti-thrombotic agents. To improve hemocompatibility in an extracorporeal circuit, replication of the anti-thrombotic and anti-inflammatory properties of the endothelium is ideal. Surface modifications can be classified into three major groups: biomimetic surfaces (heparin, nitric oxide, and direct thrombin inhibitors); biopassive surfaces [phosphorylcholine, albumin, and poly- 2-methoxyethylacrylate]; and endothelialization of blood contacting surface. The focus of this paper will be to review both present and future novel surface modifications that can obviate the need for systemic anticoagulation during extracorporeal life support therapies

Early highly effective versus escalation treatment approaches in relapsing multiple sclerosis

Treatment decisions in multiple sclerosis are complex given the large number of disease-modifying therapies with diverse safety and efficacy profiles. The importance of early treatment has been recognised but how intensively to treat at onset is not known. Substantial variability exists in treatment selection with weak clinical trial evidence to guide initial treatment choices. Decision-making is made more complicated by variable tolerance for risk of side-effects and inability to accurately predict treatment response. Whether to use moderately effective and safe medications with escalation as needed, or to use higher efficacy medications from the outset, is a key question in clinical practice. Clinical trials in patients with relapsing multiple sclerosis have focused on pairwise comparisons but the effectiveness of different treatment approaches has not been tested. Future pragmatic randomised clinical trials and observational studies will help to inform more rational selection of initial therapies and improve the quality of life of patients with relapsing multiple sclerosis

Adsorption of aspartic acid on Ni{100}: a combined experimental and theoretical study

Understanding the interaction of amino acids with metal surfaces is essential for the rational design of chiral modifiers able to confer enantioselectivity to metal catalysts. We present here an investigation of the adsorption of aspartic acid (Asp) on the Ni{100} surface, using a combination of synchrotron X-Ray Photoelectron Spectroscopy (XPS) and Near-Edge X-ray Absorption Fine Structure (NEXAFS), and Density Functional Theory (DFT) simulations. Based on the combined analysis of the experimental and simulated data, we can identify the dominant mode of adsorption as a pentadentate configuration with three O atoms at the bridge sites of the surfaces, and the remaining oxygen atom and the amino nitrogen are located on atop sites. From temperature-programmed XPS measurements it was found that Asp starts decomposing above 400 K, which is significantly higher than typical decomposition temperatures of smaller organic molecules on Ni surfaces. Our results offer valuable insights for understanding the role of Asp as a chiral modifier of nickel catalyst surfaces for enantioselective hydrogenation reactions

Benefits of early treatment with natalizumab: A real-world study

BACKGROUND: The impact of early versus later high-efficacy disease-modifying therapy (DMT) in patients with multiple sclerosis (MS) is uncertain. This study reported the association of early versus later natalizumab treatment with real-world clinical outcomes in MS patients. METHODS: The study included 661 participants diagnosed with MS in 1994 or later from 7 US centers participating in the MS Partners Advancing Technology for Health Solutions (MS PATHS) network. Time to natalizumab treatment between diagnosis and first infusion (TTNT) was determined from the Tysabri Outreach: Unified Commitment to Health (TOUCH) registry. Clinical outcomes were defined using neuroperformance tests included in the Multiple Sclerosis Performance Test. Associations were tested using TTNT as a categorical and continuous variable. Linear mixed models addressed within-subject and within-site clustering. RESULTS: TTNT varied from 0.1 to 19.8 years (median [interquartile range] 4.2 [1.8, 9.0] years). A significant association between later natalizumab use and worse outcomes was demonstrated for walking speed (p \u3c 0.001), processing speed (p \u3c 0.001), manual dexterity (p \u3c 0.001), brain atrophy (p = 0.001), and T2 lesion volume (p = 0.02). Covariate-adjusted modelling of a sensitivity population diagnosed with MS in 2006 or later (n = 424) demonstrated significant associations between longer TTNT and worse walking speed (p \u3c 0.05), processing speed (p \u3c 0.001), and manual dexterity (p \u3c 0.001). CONCLUSION: Later initiation of natalizumab was associated with worse clinical and radiologic imaging outcomes. Thus, high-efficacy DMT may have greater benefit when started earlier in MS patients. These results provide a rationale for randomized controlled trials to further assess the impact of early highly-effective DMT use versus later escalation of therapy

Clinical observation during alemtuzumab administration

• Alemtuzumab has been associated with stroke and cervicocephalic dissections. • Monitoring blood pressure is currently recommended by the EMA. • Monitoring blood pressure is not useful in predicting these rare side effects

Fingolimod: therapeutic mechanisms and ocular adverse effects.

Fingolimod is an oral immunomodulating drug used in the management of relapsing-remitting multiple sclerosis (RRMS). We aim to review the published literature on ocular manifestations of fingolimod therapy and their possible underlying mechanisms. The therapeutic effects of fingolimod are mediated via sphingosine receptors, which are found ubiquitously in various organs, including lymphoid cells, central nervous system, cardiac myocytes, and smooth muscle cells. Fingolimod-associated macular oedema (FAME) is the most common ocular side effect but retinal haemorrhages and retinal vein occlusion can occur. The visual consequences appear to be mild and, in cases of FAME, resolution is often attained with discontinuation of therapy. However, in cases of retinal vein occlusion, discontinuation of fingolimod alone may not be sufficient and intra-vitreal therapy may be required. We also propose a pragmatic service pathway for monitoring patients on fingolimod therapy, which includes stratifying them by risk and visual acuity

Multiple sclerosis management during the COVID-19 pandemic

Altres ajuts: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The development of standardized data collection as part of routine clinical care through Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) was developed and implemented at CC, JH, and CEMCAT in partnership with Biogen. Biogen did not have involvement in study design, data analysis or interpretation, or manuscript preparation.People with multiple sclerosis (MS) may be at higher risk for complications from the 2019 coronavirus (COVID-19) pandemic due to use of immunomodulatory disease modifying therapies (DMTs) and greater need for medical services. To evaluate risk factors for COVID-19 susceptibility and describe the pandemic's impact on healthcare delivery. Surveys sent to MS patients at Cleveland Clinic, Johns Hopkins, and Vall d'Hebron-Centre d'Esclerosi Múltiple de Catalunya in April and May 2020 collected information about comorbidities, DMTs, exposures, COVID-19 testing/outcomes, health behaviors, and disruptions to MS care. There were 3028/10,816 responders. Suspected or confirmed COVID-19 cases were more likely to have a known COVID-19 contact (odds ratio (OR): 4.38; 95% confidence interval (CI): 1.04, 18.54). In multivariable-adjusted models, people who were younger, had to work on site, had a lower education level, and resided in socioeconomically disadvantaged areas were less likely to follow social distancing guidelines. 4.4% reported changes to therapy plans, primarily delays in infusions, and 15.5% a disruption to rehabilitative services. Younger people with lower socioeconomic status required to work on site may be at higher exposure risk and are potential targets for educational intervention and work restrictions to limit exposure. Providers should be mindful of potential infusion delays and MS care disruption

Determining the effectiveness of early intensive versus escalation approaches for the treatment of relapsing-remitting multiple sclerosis: The DELIVER-MS study protocol

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access