Worsening of lymphopenia in patients with multiple sclerosis when switched from dimethyl fumarate to diroximel fumarate.

BACKGROUND: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are similar disease-modifying therapies (DMTs) that reduce disease activity in patients with relapsing-remitting multiple sclerosis (MS). We expect that patients on DRF would experience a similar incidence and severity of lymphopenia, given that it is a well-documented side effect of DMF treatment. METHODS: We utilized linear mixed-effects models to test for differences in white blood cell count (WBC), absolute lymphocyte count (ALC), absolute CD3+ count, absolute CD4+ count, and absolute CD8+ count over time in clinically stable patients with MS on DMF who switched to DRF. RESULTS: Twenty-two patients with MS who were clinically stable on DMF switched to DRF. Linear mixed-effects models showed a decrease in ALC when switching medications (ß = -225.70, p < 0.040). In addition, the models showed a decrease in absolute CD8+ counts after switches from DMF to DRF (ß = -85.59, p = 0.034). CONCLUSION: Patients with MS who are stable on DMF and switch to DRF may experience worsening of lymphopenia and lower absolute CD8+ counts, which may increase their risk of opportunistic infections. These findings indicate that close lymphocyte subset monitoring is clinically important when switching patients with MS from DMF to DRF.

Clinical course of multiple sclerosis with comorbid endometriosis: A matched cohort study.

BACKGROUND: Endometriosis (EMS) is pain syndrome in which endometrial tissue grows outside the uterus. EMS is associated with an increased risk of multiple sclerosis (MS), a demyelinating disease of the central nervous system. OBJECTIVE: To characterize clinical phenotypes of a cohort of patients with both EMS and MS compared to a cohort of matched controls with only MS. METHODS: We retrospectively identified patients with EMS and MS at Beth Israel Deaconess Medical Center (BIDMC). We collected data on EMS treatments and analyzed differences in histories of gynecological cancer, smoking, fatigue, anxiety, depression, headache, and neuropathic pain compared to matched controls. We used Wilcoxon signed rank tests for paired samples to compare Expanded Disability Status Scores (EDSS) and timed 25-foot walk values (T25FW). RESULTS: Using a case-control methodology, we found significantly increased EDSS (p < 0.001) and T25FW (p = 0.01) in the EMS-MS group compared to the MS group. More patients in the EMS-MS group had histories of smoking, anxiety, depression, and headaches, while more patients in the MS group had histories of fatigue and neuropathic pain. CONCLUSION: When controlling for age, race, and MS therapy, those with EMS-MS experience more MS disability than controls, suggesting this population requires more monitoring and efficacious treatment.

MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation.

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κß) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.