scholarly journals Fingolimod Potentiates the Antifungal Activity of Amphotericin B

2021 ◽  
Vol 11 ◽  
Author(s):  
Lu-Qi Wei ◽  
Jing-Cong Tan ◽  
Yue Wang ◽  
Yi-Kun Mei ◽  
Jia-Yu Xue ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Pathogens ◽  
Oral Treatment ◽  
Severe Infection ◽  
Human Fungal Pathogen ◽  
Incidence And Mortality ◽  
Relapsing Remitting ◽  
Golden Standard ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Macrophage Killing

Candida albicans (C. albicans) is an opportunistic human fungal pathogen that can cause severe infection in clinic. Its incidence and mortality rate has been increasing rapidly. Amphotericin B (AMB), the clinical golden standard antifungal agent, has severe side effects that limit its clinical application. Thus, lowering the concentration and increasing the efficacy of AMB in a combinatorial antifungal therapy have been pursued by both industry and academia. Here we identify that fingolimod (FTY720), an immunomodulatory drug used for oral treatment of relapsing-remitting multiple sclerosis, can potentiate the efficacy of AMB against C. albicans growth synergistically. Furthermore, we observe an antifungal efficacy of FTY720 in combination with AMB against diverse fungal pathogens. Intriguingly, cells treated with both drugs are hypersensitive to endothelial endocytosis and macrophage killing. This is later found to be due to the hyperaccumulation of reactive oxygen species and the corresponding increase in activities of superoxide dismutase and catalase in the cells that received combinatorial treatment. Therefore, the combination of AMB and FTY720 provides a promising antifungal strategy.

scholarly journals Telemedicine during the Coronavirus Disease (COVID-19) Pandemic: A Multiple Sclerosis (MS) Outpatients Service Perspective

2021 ◽  
Vol 13 (1) ◽  
pp. 25-31
Author(s):  
Francesco Corea ◽  
Silvia Ciotti ◽  
Antonella Cometa ◽  
Claudia De Carlo ◽  
Giancarlo Martini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Care Delivery ◽  
Oral Treatment ◽  
Case Series ◽  
Patient Characteristics ◽  
Stroke Care ◽  
Retrospective Case ◽  
Short Disease Duration ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: During the COVID-19 pandemic, the need for a broader implementation of telemedicine for many diseases has become apparent. Televisits are one type of telemedicine in which clinical visits are conducted remotely using an audio-visual connection with the patient at home. The use of televisits is more established in Stroke care but was also recently formally evaluated for Multiple Sclerosis (MS). This retrospective case series describes patient characteristics and reasons for televisits in persons with MS during the COVID-19 pandemic outbreak in Italy, which was declared in February 2020. Methods: Recruitment occurred in a general hospital based MS clinic during Italy’s lockdown months period (9 March–18 May). Each subject completed at least one televisit. The baseline data included were demographics and MS history; reasons for the remote house calls were analyzed focusing on COVID-19 related needs. Results: Forty-six participants completed at least one study visit. The patients enrolled were more often females suffering from Relapsing Remitting Multiple Sclerosis (RRMS). Half of the patients had an intermediate level of education and lived within a 60 min drive from the clinic. These patients predominately had a short disease duration and were mostly involved in oral treatment. The main reasons for the call were drug use and counseling on social distancing. In 5 cases, COVID-19 infection was reported. Conclusions: Televisits during the COVID-19 outbreak demonstrated their utility as a care delivery method for MS. Hence, it is vital to facilitate the implementation of this technology in common practice to both face infectious threats and increase accessibility of the health care system.

scholarly journals Severe rebound after cessation of fingolimod treated with ocrelizumab with coincidental transient aggravation: report of two cases

2019 ◽  
Vol 12 ◽  
pp. 175628641984681 ◽  
Author(s):  
Stephan Schmidt ◽  
Thomas Schulten
Keyword(s):  
Multiple Sclerosis ◽  
Monoclonal Antibody ◽  
Immune Reconstitution ◽  
Oral Treatment ◽  
Expanded Disability Status Scale ◽  
Radiological Findings ◽  
Highly Active ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis

Background: Fingolimod (FTY), an oral treatment for patients with relapsing-remitting multiple sclerosis (RRMS), has been associated with a significant rebound of disease activity after cessation of therapy. Methods: We present the clinical and radiological findings of two patients with severe rebound after FTY withdrawal, which was further aggravated by the initiation of treatment with the B cell-depleting monoclonal antibody, ocrelizumab. Results: Both patients exhibited significant Expanded Disability Status Scale progression after administration of ocrelizumab despite immune reconstitution more than 3 months after FTY withdrawal. Conclusions: Although the observed effect may be coincidental, ocrelizumab may complicate recovery of rebound after cessation of FTY. Further studies are warranted to better understand and predict the clinical and immunological consequences of sequential immunosuppressive and immunomodulatory treatments in patients with highly active RRMS.

scholarly journals Epidemiology and therapeutic management of highly active relapsing-remitting multiple sclerosis adults in the French national health insurance database

2021 ◽  
Author(s):  
Arnaud Kwiatkowski ◽  
Marianne Payet ◽  
Emmanuelle Préaud ◽  
Ludovic Lamarsalle ◽  
Fanny Raguideau ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Therapeutic Management ◽  
Specific Information ◽  
Discharge Data ◽  
Highly Active ◽  
Incidence And Mortality ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Insurance Database

Abstract Background: In France, no specific information on the Highly Active Relapsing-Remitting Multiple Sclerosis (HA-RRMS) population is available.Objective: To describe the epidemiology and therapeutic management of HA-RRMS patients in France.Methods: In this cohort study, HA-RRMS patients were identified in the health data system with a new algorithm using outpatient healthcare consumption and hospital discharge data. Results: Over 2010–2015, 9,596 incident HA-RRMS patients were identified (sex ratio: 2.8; mean age 39.9 years old) and followed-up for 4.0 years, on average. In 2015, the incidence and mortality rates in patients aged 20 and above were 3.6 and 389 per 100,000, respectively (lower mortality than in the MS population but twice as high as in the French population). During the study, 39.7% of patients took a disease-modifying drug (DMD) and 83.5% a high efficacy DMD (HE-DMD, fingolimod or natalizumab, with a mean treatment duration of 3.5 years). When patients treated by an HE-DMD required to switch to another treatment, it was more often to the other HE-DMD (more often from natalizumab to fingolimod) than to a DMD. Conclusions: According to this first real-world study, HA-RRMS patients could represent 8% of MS patients. The results validated the algorithm to identify HA-RRMS patients.

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