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Visualizing the target estimand in comparative effectiveness studies with multiple treatments.

Aim: Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bi … rpretation of target estimands in a case study comparing the effectiveness of teriflunomide (TERI), dimethyl fumarate (DMF) and natalizumab (NAT) on manual dexterity in patients with multiple sclerosis. Results: In the simulation study, estimates of the treatment effect greatly differed depending on the target population. For example, when comparing treatment B wit …

Safety, tolerability, and efficacy of diroximel fumarate in a cohort of Black patients with multiple sclerosis from the phase 3 EVOLVE-MS-1 study.

BACKGROUND: Multiple sclerosis (MS) has not been well studied in racial and ethnic minorities, as these populations are typically underrepresented in clinical trials. Black or African Americans comprise ∼13 % of the US population, yet are represented by as little as 5 % in clinical trials. Differences in disease course and progression have been reported between races and ethnicities, so there is a need to understand the safety and efficacy of disease-modifying therapies (DMTs) in Black patients, to inform evidence-based approaches to treatment in this population. METHODS: EVOLVE-MS-1 (NCT0234

Активаторы Nrf2 для лечения редких заболеваний, связанных с перегрузкой железа: от скамейки до кровати.

Железная перегрузка и связанные с ней окислительные повреждения наблюдаются во многих редких болезнях в результате мутации генов, связанных с гомеостазом железа. Будучи основным регулятором реакции на клеточную антиоксидантную реакцию, Nrf2 может также снизить системный и клеточный уровень железа путем регулирования генов и путей, связанных с железом, что делает Nrf2 очень хорошими инициаторами для лечения нарушений, связанных с перегрузкой железа. К числу успешных примеров относится клиническое использование омавельоксолона для атаксии Фридрейха и диметилфумарата для повторного излучающего мн

Совпадение в аннотации оригинала
Iron overload and related oxidative damage are seen in many rare diseases, due to mutation of iron homeostasis-related genes. As a core regu … isorders. Successful examples include the clinical use of omaveloxolone for Friedreich's Ataxia and dimethyl fumarate for relapsing-remitting multiple sclerosis. Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanism …

Lymphopenia is Not the Primary Therapeutic Mechanism of Diroximel Fumarate in Relapsing-Remitting Multiple Sclerosis: Subgroup Analyses of the EVOLVE-MS-1 Study.

INTRODUCTION: In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia. METHODS: EVOLVE-MS-1-an open-label, 96-week, phase 3 study-assessed DRF safety and exploratory efficacy in patients with relapsing-remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients…

Scleroderma pulmonary arterial hypertension: the same as idiopathic pulmonary arterial hypertension?

PURPOSE OF REVIEW: Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc), which confers significant mor … lier in the course of their disease. Novel therapies specifically for SSc-PAH such as rituximab and dimethyl fumarate are under investigation. SUMMARY: Although patients with SSc-PAH and IPAH present with similar symptoms, there are significant differences between these two forms of PAH that warrant further investigation and characterization of optimal detection s …

VOC emitted by biopharmaceutical industries: Source profiles, health risks, and secondary pollution.

The biopharmaceutical industry contributes substantially to volatile organic compounds (VOCs) emissions, causing growing concerns and social developmental conflicts. This study conducted an on-site investigation of the process-based emission of VOCs from three biopharmaceutical enterprises. In the workshops of the three enterprises, 26 VOCs were detected, which could be sorted into 4 classes: hydrocarbons, aromatic hydrocarbons, oxygen-containing compounds, and nitrogen-containing compounds. Ketones were the main components of waste gases, accounting for 44.13%-77.85% of the overall VOCs. Proc

[Clinical variables and management of disseminated granuloma annulare - monocentric retrospective analysis of 33 cases between 2021 and 2023].

BACKGROUND AND OBJECTIVES: Granuloma annulare (GA) is a noninfectious, granulomatous dermatosis that is generally localized and self-limitin … Topical glucocorticoids, systemic glucocorticoids, phototherapy, topical calcineurin inhibitors and dimethyl fumarate were used therapeutically in descending frequency. Only 6 patients (18%) showed partial or complete remission. CONCLUSION: Due to the lack of approved therapies, disseminated GA is treated with inadequately effective regimens. Prospective randomize …

Natalizumab and fumarate treatment differentially modulate CD4+ T cell and B cell subtypes in multiple sclerosis patients without impacting durable COVID-19 vaccine responses.

BACKGROUND: There is a greater risk of complications from severe COVID-19 in immunocompromised patients with multiple sclerosis (pwMS) treated with certain disease-modifying therapies (DMTs), as well as a diminished vaccine response. METHODS: In this exploratory, observational study, we recruited 28 patients with Relapsing Remitting MS (RRMS, n=24) or Secondary Progressive MS (SPMS, n=4), that were receiving treatment with either natalizumab or fumarates (diroximel or dimethyl) prior to baseline sample collection. Blood samples were collected before vaccination (baseline), between 4 weeks and

C-reactive protein thresholds for discriminating active disease in axial spondyloarthritis: should we lower them?

BACKGROUND: Maternal Western diet (WD) consumption during pregnancy is linked to adverse gestational and offspring metabolic outcomes. Dimethyl fumarate (DMF), a Nrf2 activator with antioxidant and anti-inflammatory properties, is a proposed therapeutic candidate, but its safety and efficacy during pregnancy remain unexplored. This pilot study aimed to establish a guinea pig model of gestational WD consumption and evaluate the feasibility of DMF treatment on maternal, placental, and fetal outcomes. METHODS: Pregnant guinea pigs consuming a modified WD were randomized to receive either DMF or …

S-Nitrosylation of Histone Deacetylase 2 by Neuronal Nitric Oxide Synthase as a Mechanism of Diastolic Dysfunction.

BACKGROUND: Although the clinical importance of heart failure with preserved ejection fraction has been extensively explored, most therapeut … rosylation-resistant were also challenged. N(ω)-propyl-L-arginine, an nNOS selective inhibitor, and dimethyl fumarate, an NRF2 (nuclear factor erythroid 2-related factor 2) inducer, were used. Molecular events were further checked in human left ventricle specimens. RESULTS: SAUNA or mild transverse aortic constriction stress impaired diastolic function and exercis …

Very low monomethyl fumarate exposure via human milk: a case report-a contribution from the ConcePTION project.

INTRODUCTION: While breastfeeding is recommended, knowledge regarding medicine transfer to human milk and its safety for nursing infants is limited. Only one paper has previously described dimethyl fumarate (DMF) transfer during breastfeeding in two patients at 5 and 6 months postpartum, respectively. The current case report describes maternal pharmacokinetic data of monomethyl fumarate (MMF), the active metabolite of DMF, and infant exposure estimations of MMF at 3 months postpartum. METHODS: A 32-year-old Caucasian woman started DMF therapy (120 mg, 2x/day) for multiple sclerosis at 3 month…

Guaianolide Sesquiterpene Lactones from Globe Artichoke (Cynara scolymus L.) Induce Nrf2-Associated Antioxidant Signaling.

Background/Objectives: Oxidative and electrophilic stress-response pathways contribute to cellular resilience across various chronic diseases, including neurodegenerative, hepatic, and metabolic disorders. Pharmacological activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is a validated strategy to counteract oxidative damage, as evidenced by the clinical approval of dimethyl fumarate (DMF) and monomethyl fumarate (MMF) for relapsing forms of multiple sclerosis; both electrophilic compounds activate Nrf2 via covalent Keap1 (Kelch-lik…

Monomethyl fumarate confers cardioprotection after myocardial infarction via HCAR2-dependent activation of PI3K/Akt signaling.

Monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate, an immunomodulatory drug approved for multiple sclerosis and psoriasis, has emerging potential in ischemic heart disease. We investigated whether MMF can attenuate myocardial infarction (MI) injury and delineated the underlying mechanisms, focusing on hydroxycarboxylic acid receptor 2 (HCAR2, also known as GPR109A) and PI3K/Akt signaling. In a mouse MI model induced by permanent left anterior descending coronary artery ligation, MMF administration prior to ischemia significantly preserved left ventricular function and reduc…

Безопасность и эффективность дироксимеля фумарата в повторной форме множественного склероза: систематический обзор и метаанализ.

ЦЕЛЬ: Оценка безопасности и эффективности Diroximel Fumarate (DRF) у пациентов с различными формами восстановления MS (RMS) на основе систематического обзора и метаанализа. МЕТОДЫ: Был проведен систематический обзор и метаанализ в соответствии с руководящими принципами ПРИСМА. Базы данных < < Скопус > > , < < Пубмед > > и < < Кокран > > CNTRAL были подвергнуты обыску до декабря 6, 2024, для клинических испытаний и наблюдений за ДРР в РСМ. К числу критериев приемлемости относятся исследования, посвященные оценке безопасности или эффективности ОРР, за исключен

Совпадение в аннотации оригинала
OBJECTIVE: To evaluate the safety and efficacy of Diroximel Fumarate (DRF) in patients with different relapsing forms of MS (RMS) through sy … ficacy in reducing relapse rates and offers an improved safety profile compared to its predecessor, Dimethyl Fumarate (DMF), particularly in GI tolerability. However, lymphopenia requires monitoring. Further research is recommended to evaluate long-term safety and efficacy in diverse populations.

TCA Cycle Intermediate Mitigates Di(2-ethylhexyl) Phthalate-Induced Cholestatic Liver Injury Through Modulation of the Nrf2/NQO1 Signalling Axis.

As a commonly used phthalate compound, di(2-ethylhexyl) phthalate (DEHP) has been shown to disrupt the tricarboxylic acid (TCA) cycle and aggravate tissue damage. However, whether the TCA cycle is involved in cholestatic liver injury (CLI) induced by DEHP and the protective effect of dimethyl fumarate (DMF), which is used to supplement TCA intermediate metabolites, remained unclear. Here, mice were randomized into five groups (n = 6/group): (1) Control, (2) DEHP (200 mg/kg/day), (3) DMF (100 mg/kg/day), (4) DEHP + DMF (30 mg/kg/day) and (5) DEHP + DMF (100 mg/kg/day). Our data demonstrated tha…

Programmed cell death inhibitors: a new hope for cancer therapy?

BACKGROUND: Tumor initiation and progression are dynamically regulated by multiple programmed cell death (PCD) pathways. In recent years, be … el cell death modalities, such as the necroptosis inhibitor necrostatin-1, the pyroptosis inhibitor dimethyl fumarate, and the ferroptosis inhibitor ferrostatin-1, in anti-tumor therapy, providing theoretical foundations and novel perspectives for improving patient prognosis.

Nrf2 modulates the IRF7-SLC31A1 axis to suppress neuronal cuproptosis after traumatic brain injury.

Traumatic brain injury (TBI) is one of the most prevalent neurological disorders and a major cause of death and disability worldwide. Cuprop … cuproptosis after TBI, primarily through IRF7-mediated upregulation of SLC31A1. The Nrf2 activator dimethyl fumarate (DMF) suppresses neuronal injury and improves neurological function in TBI mice by inhibiting cuproptosis. Our results establish that cuproptosis is an important mechanism in TBI and that activation of Nrf2 mitigates TBI-induced cuproptosis by regul …

Relapsing-remitting multiple sclerosis in a patient with Huntington's disease.

A woman in her 50s with genetically confirmed Huntington's disease presented with right-sided arm sensory symptoms that evolved over days an … was established, based on the 2024 McDonald criteria and after exclusion of alternative diagnoses. Dimethyl fumarate was initiated, with neither adverse effects nor new clinical relapses or MRI lesions. This case highlights the need to remain alert to subjective neurological symptoms in patients with Huntington's disease, ensuring that new manifestations are not a …

Neuroprotective effects of glucotropaeolin as the major glucosinolate of cress seed on cuprizone-induced mouse model of multiple sclerosis.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and myelin damage. Glucosinolates, present in Lepidium sativum L. (garden cress) seeds (LSS), exhibit anti-inflammatory properties. This study evaluates the anti-inflammatory and neuroprotective effects of glucosinolate-rich and volatile fractions from LSS in a MS mouse model. C57BL/6 male mice were divided into seven groups: Normal, cuprizone (0.4% diet for 8 weeks), positive control (dimethyl fumarate), and groups receiving LSS glucosinolate (1, 10 mg/kg, oral) and volatile fractions (1, 10 mg/kg, subcutaneo…

Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice.

The treatment of osteoporosis and related bone defects remains challenging. This study identifies pyroptosis-driven inflammation as a key disruptor of bone homeostasis. To address this, we develop a magnesium-gelatin composite microsphere scaffold (GelMa/Mg/DMF MS) that exploit pyroptosis blockade and hydrogen-mediated inflammation regulation for osteoporosis treatment. This porous microsphere scaffold is implanted into bone defects to achieve the sustained release of hydrogen gas, magnesium ions (Mg2+), and dimethyl fumarate (DMF). DMF act by activating the nuclear factor erythroid-related fa…