Benef Microbes. 2020 Oct 13;:1-16
Authors: Libbey JE, Sanchez JMS, Fleming BA, Doty DJ, DePaula-Silva AB, Mulvey MA, Fujinami RS
Abstract
Multiple sclerosis (MS) is a neuro-inflammatory autoimmune disease of the central nervous system (CNS) that affects young adults. It is characterised by the development of demyelinating lesions and inflammation within the CNS. Although the causes of MS are still elusive, recent work using patient samples and experimental animal models has demonstrated a strong relationship between the gut microbiota and its contribution to CNS inflammation and MS. While there is no cure for MS, alteration of the gut microbiota composition through the use of probiotics is a very promising treatment. However, while most recent works have focused on the use of probiotics to modify pre-existing disease, little is known about its role in protecting from the establishment of MS. In this study, we determined whether colonisation with the probiotic bacterium Escherichia coli strain Nissle 1917 (EcN) could be used as a prophylactic strategy to prevent or alter the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We found that double gavage (two doses) of EcN before induction of EAE delayed disease onset and decreased disease severity. We also found that EcN-treated mice had decreased amounts of perivascular cuffing, CD4+ T cell infiltration into the CNS, together with significantly decreased absolute numbers of Th1 cells, and reduced activation of microglia. Although further studies are necessary to comprehend the exact protective mechanisms induced, our study supports a promising use of EcN as a probiotic for the prevention of MS.
PMID: 33045841 [PubMed - as supplied by publisher]
Ann Neurol. 2020 07;88(1):42-55
Authors: Krysko KM, Graves JS, Rensel M, Weinstock-Guttman B, Rutatangwa A, Aaen G, Belman A, Benson L, Chitnis T, Gorman M, Goyal MS, Harris Y, Krupp L, Lotze T, Mar S, Moodley M, Ness J, Rodriguez M, Rose J, Schreiner T, Tillema JM, Waltz M, Casper TC, Waubant E, US Network of Pediatric MS Centers
Abstract
OBJECTIVE: To assess real-world effectiveness of initial treatment with newer compared to injectable disease-modifying therapies (DMTs) on disease activity in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS).
METHODS: This is a cohort study of children with MS/CIS followed at 12 clinics in the US Network of Pediatric MS Centers, who received initial therapy with newer (fingolimod, dimethyl fumarate, teriflunomide, natalizumab, rituximab, ocrelizumab) or injectable (interferon-β, glatiramer acetate) DMTs. Propensity scores (PSs) were computed, including preidentified confounders. Relapse rate while on initial DMT was modeled with negative binomial regression, adjusted for PS-quintile. Time to new/enlarging T2-hyperintense and gadolinium-enhancing lesions on brain magnetic resonance imaging were modeled with midpoint survival analyses, adjusted for PS-quintile.
RESULTS: A total of 741 children began therapy before 18 years, 197 with newer and 544 with injectable DMTs. Those started on newer DMTs were older (15.2 vs injectable 14.4 years, p = 0.001) and less likely to have a monofocal presentation. In PS-quintile-adjusted analysis, those on newer DMTs had a lower relapse rate than those on injectables (rate ratio = 0.45, 95% confidence interval (CI) = 0.29-0.70, p < 0.001; rate difference = 0.27, 95% CI = 0.14-0.40, p = 0.004). One would need to treat with newer rather than injectable DMTs for 3.7 person-years to prevent 1 relapse. Those started on newer DMTs had a lower rate of new/enlarging T2 (hazard ratio [HR] = 0.51, 95% CI = 0.36-0.72, p < 0.001) and gadolinium-enhancing lesions (HR = 0.38, 95% CI = 0.23-0.63, p < 0.001) than those on injectables.
INTERPRETATION: Initial treatment of pediatric MS/CIS with newer DMTs led to better disease activity control compared to injectables, supporting greater effectiveness of newer therapies. Long-term safety data for newer DMTs are required. ANN NEUROL 2020 ANN NEUROL 2020;88:42-55.
PMID: 32267005 [PubMed - indexed for MEDLINE]
Mil Med. 2020 01 07;185(Suppl 1):296-302
Authors: Redd AM, Gundlapalli AV, Suo Y, Pettey WBP, Brignone E, Chin DL, Walker LE, Poltavskiy EA, Janak JC, Howard JT, Sosnov JA, Stewart IJ
Abstract
INTRODUCTION: We explore disparities in awarding post-traumatic stress disorder (PTSD) service-connected disability benefits (SCDB) to veterans based on gender, race/ethnicity, and misconduct separation.
METHODS: Department of Defense data on service members who separated from October 1, 2001 to May 2017 were linked to Veterans Administration (VA) administrative data. Using adjusted logistic regression models, we determined the odds of receiving a PTSD SCDB conditional on a VA diagnosis of PTSD.
RESULTS: A total of 1,558,449 (79% of separating service members) had at least one encounter in VA during the study period (12% female, 4.5% misconduct separations). Females (OR 0.72) and Blacks (OR 0.93) were less likely to receive a PTSD award and were nearly equally likely to receive a PTSD diagnosis (OR 0.97, 1.01). Other racial/ethnic minorities were more likely to receive an award and diagnosis, as were those with misconduct separations (award OR 1.3, diagnosis 2.17).
CONCLUSIONS: Despite being diagnosed with PTSD at similar rates to their referent categories, females and Black veterans are less likely to receive PTSD disability awards. Other racial/ethnic minorities and those with misconduct separations were more likely to receive PTSD diagnoses and awards. Further study is merited to explore variation in awarding SCDB.
PMID: 32074380 [PubMed - indexed for MEDLINE]
Mil Med. 2020 01 07;185(Suppl 1):413-419
Authors: Gundlapalli AV, Redd AM, Suo Y, Pettey WBP, Brignone E, Chin DL, Walker LE, Poltavskiy EA, Janak JC, Howard JT, Sosnov JA, Stewart IJ
Abstract
INTRODUCTION: Musculoskeletal (MSK) conditions are commonly seen among military service members (SM) and Veterans. We explored correlates of award of MSK-related service-connected disability benefits (SCDB) among SM seeking care in Veterans Affairs (VA) hospitals.
MATERIALS AND METHODS: Department of Defense data on SM who separated from October 1, 2001 to May 2017 were linked to VA administrative data. Using adjusted logistic regression models, we determined the odds of receiving MSK SCDB.
RESULTS: A total of 1,558,449 (79% of separating SM) had at least one encounter in VA during the study period (7.8% disability separations). Overall, 51% of this cohort had at least one MSK SCDB (88% among disability separations, 48% among normal). Those with disability separations (as compared to normal separations) were significantly more likely to receive MSK SCDB (odds ratio 2.37) as were females (compared to males, odds ratio 1.15).
CONCLUSIONS: Although active duty SM with disability separations were more likely to receive MSK-related service-connected disability ratings in the VA, those with normal separations also received such awards. Identifying those at highest risk for MSK-related disability could lead to improved surveillance and prevention strategies in the Department of Defense and VA health care systems to prevent further damage and disability.
PMID: 32074349 [PubMed - indexed for MEDLINE]
