A Real-World Prospective Multiple Sclerosis Pregnancy Registry in the United States: PREG-MS.

Background And Objectives: Multiple sclerosis (MS) affects more than 1 million people in the United States, including reproductive-age women. There has been a paucity of prospective, pregnancy registries based on MS disease rather than medication exposures. A prospective MS pregnancy registry (PREG-MS) was established in 2017 as a prospective, single-cohort, real-world MS pregnancy registry in New England States of the United States, with goals to evaluate (1) course of MS and disease-modifying therapies (DMT) use during conception attempts and in the peripartum period, (2) pregnancy outcomes in women with MS (WwMS), and (3) longer-term developmental outcomes in offspring of WwMS.

High Efficacy Two-Stage Metal Treatment Incorporating Basic Oxygen Furnace Slag and Microbiological Sulfate Reduction.

Lignocellulosic sulfate-reducing biochemical reactors (SRBRs) can be implemented as passive treatment for mining-influenced water (MIW) mitigating the potentially deleterious effects of MIW acidic pH, and high concentrations of metal(loid)s and SO. In this study, a novel two-stage treatment for MIW was designed, where basic oxygen furnace slag (slag stage) and microbial SO reduction (SRBR stage) were incorporated in series. The SRBRs contained spent brewing grains or sugarcane bagasse as sources of lignocellulose.

Preserved T cell but attenuated antibody response in MS patients on fingolimod and ocrelizumab following 2nd and 3rd SARS-CoV-2 mRNA vaccine.

Background: There is limited knowledge about T cell responses in patients with multiple sclerosis (MS) after 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine.

Objectives: Assess the SARS-CoV-2 spike antibody and T cell responses in MS patients and healthy controls (HCs) after 2 doses (2-vax) and 3 doses (3-vax) of SARS-CoV-2 mRNA vaccination.

Methods: We studied seroconversion rates and T cell responses by flow cytometry in HC and MS patients on fingolimod or ocrelizumab.

Humoral response to COVID-19 vaccination in MS patients on disease modifying therapy: Immune profiles and clinical outcomes.

Background: Patients with multiple sclerosis (MS) on some disease modifying therapies (DMTs), particularly anti-CD20 and sphingosine-1-phosphate (S1P) modulators, are at increased risk of severe Coronavirus Disease 19 (COVID-19) and death. COVID-19 vaccinations are effective in preventing infection and severe disease, but humoral response to vaccination and outcomes of COVID-19 infection after vaccination in MS patients on DMTs remain less understood.

Methods: In this retrospective single-center study, patients enrolled in the CLIMB (Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital) study and biorepository who had been vaccinated against COVID-19 and had SARS-CoV-2 spike antibody (anti-SARS-CoV-2 S Roche-Elecsys) testing were identified and compared to healthy controls.

COVID-19 severity is associated with worsened neurological outcomes in multiple sclerosis and related disorders.

Background: Neurologic outcomes in patients with multiple sclerosis (MS) and related disorders (MSRD) following COVID-19 is not well understood. The objective of this study was to investigate neurologic outcomes in patients with MSRD post-COVID-19.

Methods: This was a retrospective medical records review study of adult patients with MSRD and COVID-19 infection at the Brigham MS Center.

Continuous-mode acclimation and operation of lignocellulosic sulfate-reducing bioreactors for enhanced metal immobilization from acidic mining-influenced water.

Lignocellulosic sulfate-reducing bioreactors are an inexpensive passive approach for treatment of mining-influenced water (MIW). Typically, microbial community acclimation to MIW involves bioreactor batch-mode operation to initiate lignocellulose hydrolysis and fermentation and provide electron donors for sulfate-reducing bacteria. However, batch-mode operation could significantly prolong bioreactor start-up times (up to several months) and select for slow-growing microorganisms.

Induction of immunogenic cell death of cancer cells through nanoparticle-mediated dual chemotherapy and photothermal therapy.

The use of nanomedicines to induce immunogenic cell death is a new strategy that aims to increase tumor immunogenicity and thereby prime tumors for further immunotherapies. In this study, we developed a nanoparticle formulation for combinatory chemotherapy and photothermal therapy based only on materials previously used in FDA-approved products and investigated the effect of the combinatory therapy on the growth inhibition and induction of immunogenic cell death in human MDA-MB-231 breast cancer cells. The formulation consists of ~108-nm nanoparticles made of poly(lactic acid)-b-methoxy poly(ethylene glycol) which carry doxorubicin for chemotherapy and indocyanine green for photothermal therapy.

Prospective growth and developmental outcomes in infants born to mothers with multiple sclerosis.

Background: The importance of supporting pregnancy-related decisions in multiple sclerosis (MS) patients has increasingly been recognized and hence the need for prospective data on pregnancy and pediatric outcomes in this patient population.

Objective: To assess prospective growth and developmental outcomes of infants born to mothers with multiple sclerosis (IMS).

Methods: PREG-MS is a prospective multicenter cohort study in New England, United States.

Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis.

Background: There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.

Methods: We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks.

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis.

Objective: The subcortical deep gray matter (DGM) develops selective, progressive, and clinically relevant atrophy in progressive forms of multiple sclerosis (PMS). This patient population is the target of active neurotherapeutic development, requiring the availability of outcome measures. We tested a fully automated MRI analysis pipeline to assess DGM atrophy in PMS.

Design, rationale, and baseline characteristics of the randomized double-blind phase II clinical trial of ibudilast in progressive multiple sclerosis.

Background: Primary and secondary progressive multiple sclerosis (MS), collectively called progressive multiple sclerosis (PMS), is characterized by gradual progression of disability. The current anti-inflammatory treatments for MS have little or no efficacy in PMS in the absence of obvious active inflammation. Optimal biomarkers for phase II PMS trials is unknown.

The role of biosimilar granulocyte colony stimulating factor (GCSF) Zarzio for progenitor cell mobilization and the treatment of therapy-induced neutropenia in adult hematopoietic stem cell transplantation.

Originator GCSF (Neupogen) has been used to mobilize progenitor stem cells and treat therapy-induced neutropenia in Canadian stem cell transplant settings for years. Although its benefit is not in question, viable alternatives are available. Biosimilar GCSF (Zarzio) is widely in use in Europe since 2009 and was recently approved in the U.

Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea.

Objectives: To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA.

Methods: The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians.

Health promotion, risk stratification, and treatment options to decrease hospitalization rates for community-acquired pneumonia in adults.

Purpose: Community-acquired pneumonia (CAP) is a serious illness and hospitalization for this illness is expensive. There is much the nurse practitioner (NP) can do to prevent and manage this illness.

Data Sources: Review of current literature, medical/nursing references, and data from the healthcare utilization project (HCUP).

Identification of insomnia in a sleep center population using electronic health data sources and the insomnia severity index.

Study Objectives: To assess the validity and efficacy of using electronic health data to identify a physician diagnosis of insomnia in a population of patients referred for testing at a tertiary sleep center.

Methods: Retrospective cohort study in a tertiary sleep center in Calgary, Alberta, Canada. Cohort consisted of 1,207 patients referred for sleep diagnostic testing and/or assessment by a sleep physician.

Readmissions after implantation of axial flow left ventricular assist device.

Objectives: The purpose of this study was to determine the occurrence and causes of readmissions after implantation of axial flow left ventricular assist device (LVAD).

Background: Based on the REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) study experience, readmissions after LVAD implantation are thought to be frequent.

Methods: We retrospectively analyzed admissions to our facility in a cohort of 115 patients implanted between January 2008 and July 2011 with the HeartMate II axial flow LVAD, of whom 42 were bridged to transplant.

The CD6 multiple sclerosis susceptibility allele is associated with alterations in CD4+ T cell proliferation.

Genome-wide association studies have revealed a large number of genetic associations with autoimmune diseases. Despite this progress, the mechanisms underlying the contribution of allelic variants to the onset of immune-related diseases remain mostly unknown. Our recent meta-analysis of genome-wide association studies of multiple sclerosis (MS) identified a new susceptibility locus tagged by a single nucleotide polymorphism, rs17824933 (p = 3.

Snail2 controls mesodermal BMP/Wnt induction of neural crest.

The neural crest is an induced tissue that is unique to vertebrates. In the clawed frog Xenopus laevis, neural crest induction depends on signals secreted from the prospective dorsolateral mesodermal zone during gastrulation. The transcription factors Snail2 (Slug), Snail1 and Twist1 are expressed in this region.

Enhancing nurse practitioner understanding of urachal anomalies.

Purpose: To provide nurse practitioners an understanding of urachal anomalies, their presentations, and treatment options.

Data Sources: Scientific literature, including articles that address the pathogenesis, presentation, complications, diagnosis, and treatment of acquired and congenital urachal anomalies.

Conclusion: Urachal disorders occur in 1 of 5000 persons.

Ethical analysis of withdrawing ventricular assist device support.

Objective: To describe a series of patients with heart failure supported with a ventricular assist device (VAD) who requested (or whose surrogates requested) withdrawal of VAD support and the legal and ethical aspects pertaining to these requests.

Patients And Methods: We retrospectively reviewed the medical records of patients at Mayo Clinic, Rochester, MN, from March 1, 2003, through January 31, 2009, who requested (or whose surrogates requested) withdrawal of VAD support and for whom the requests were fulfilled. We then explored the legal and ethical permissibility of carrying out such requests.

T-cells in multiple sclerosis.

Multiple sclerosis (MS) is a multifocal demyelinating disease of the central nervous system pathologically characterized by lesions of infiltrating macrophages and T cells. Multiple lines of evidence implicate that T cells play a central role in both mediating and regulating MS pathophysiology, and efforts to develop rational therapeutic strategies for MS have focused on understanding factors which control T cell function. T cells are a highly heterogeneous population comprised of multiple cell subtypes which mediate both adaptive immunity and specific tolerance.

Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses.

Multiple sclerosis (MS) is an organ-specific autoimmune disorder that is in part genetically determined. The gene encoding the alpha-chain of the IL-2 receptor, IL2RA, harbors alleles associated with risk to MS and other autoimmune diseases. In addition, IL2RA genetic variants correlate with the levels of a soluble form of the IL-2 receptor in subjects with type 1 diabetes and multiple sclerosis.

IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production.

Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus.