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Proportionate and disproportionate reporting of different infectious complications of disease modifying therapy in multiple sclerosis.

INTRODUCTION: Progessive multifocal leukoencephalopathy (PML) is a complication of immunoincompetence due to disease or immunosuppressive th … d from entries to Vigibase for a sample of drugs used for DMT (Alemtuzumab, Cladribine, Fingolimod, Dimethyl fumarate, Glatirameracetat, Interferon beta-1a, Interferon beta-1b, Natalizumab, Ocrelizumab, Ofatumumab, Ozanimod, Peginterferon-beta-1a, Ponesimod, Siponimod, and Teriflunomide) and infections with the varicella zoster virus (VZV), PML, and cryptococcal an …

The gasdermin family: from pyroptosis mechanisms to therapeutic targets.

The gasdermin (GSDM) family of proteins has emerged as the central executioner of pyroptosis, a form of inflammatory cell death characterize … tegies, encompassing small-molecule inhibitors such as disulfiram (DSF), necrosulfonamide (NSA) and dimethyl fumarate (DMF), as well as novel material-based delivery systems. Collectively, these advances underscore the therapeutic potential of targeting GSDMs for precise clinical intervention to treat both inflammatory and non-inflammatory diseases, as well as to e …

Successful Treatment of Linear Psoriasis With the IL-17a-Antagonist Ixekizumab: A Case Report.

Linear psoriasis (LP) represents a rare variant of psoriasis. The clinical presentation includes erythematous plaques distributed along the … s that proved refractory to treatment with topical corticosteroids, vitamin D analogs, and systemic dimethyl fumarate. The histopathological findings showed psoriasiform epidermal hyperplasia with alternating ortho- and parakeratosis, subepidermal capillary dilatation, and perivascular lymphocytic infiltrates, confirming the diagnosis. Ixekizumab, a IL-17A antagoni …

Инфекции у пациентов с множественным склерозом, которые лечатся с помощью методов лечения, позволяющих видоизменить заболевания: когортное исследование по сравнительной оценке риска.

Справочная информация: Основными режимами лечения множественных склерозов (МS) являются методы лечения, корректирующие заболевания (ДМТ). Обычными осложнениями этих лекарств являются грибные, вирусные и бактериальные инфекции. Кроме того, само МЗ является хроническим заболеванием, связанным с иммунизацией, которое может скомпрометировать их инфекцию. Таким образом, НР может быть фактором риска инфекционных осложнений. Методы: Настоящий документ представляет собой ретроспективное когортное исследование, проведенное с февраля 2020 по январь 2022 с использованием перспективных данных от каждого п

Совпадение в аннотации оригинала
Background: The major treatment regimens for multiple sclerosis (MS) are disease-modifying therapies (DMTs). Fungal, viral, and bacterial in … urinary tract infection (UTI) and bacterial vaginitis. Moreover, rituximab, glatiramer acetate, and dimethyl fumarate were associated with HSV-associated ulceration. None of the investigated DMTs were associated with an altered risk of COVID-19. Conclusion: The use of DMTs can result in an increased risk of infections in patients. The selection of these DMTs should …

[A patient with multiple sclerosis who developed bilateral optic neuritis and central trigeminal myelin lesion].

A 70-year-old woman was admitted to our hospital due to bilateral optic neuritis and left facial sensory disturbance that became exacerbated … elin lesion confined to the central myelin portion and high level of MBP in the CSF. Treatment with dimethyl fumarate has been effective for preventing recurrence in 13 months in this patient. The central-peripheral myelin transitional zone at the trigeminal nerve is located 1-6 mm from the pons, where central myelin changes to the peripheral myelin. This patient s …

Reviewing the Significance of Blood-Brain Barrier Disruption in Multiple Sclerosis Pathology and Treatment.

The disruption of blood-brain barrier (BBB) for multiple sclerosis (MS) pathogenesis has a double effect: early on during the onset of the i … nt of relapses, no evidence of disease activity and smoldering demyelination or silent progression. Dimethyl fumarate (DMF), modulators of S1P receptor, cladribine and laquinimode are DMTs that are able to cross the BBB and exhibit beneficial direct effects in the CNS with very different mechanisms of action, providing hope that a combined therapy might be effectiv …

Economic Evaluation of Cladribine Tablets in Patients With High Disease Activity-Relapsing-Remitting Multiple Sclerosis in the Kingdom of Saudi Arabia.

OBJECTIVE: Cladribine tablets are the first short-course oral treatment approved for high disease activity relapsing-remitting multiple scle … ure and validated by key opinion leaders. The comparators considered in the model were alemtuzumab, dimethyl fumarate, fingolimod, interferon beta-1a (subcutaneous and intramuscular) and beta-1b, natalizumab, and teriflunomide. A sensitivity analysis was also performed to assess the robustness of the analysis. RESULTS: The cost-effectiveness results showed cladrib …

Comparison of brain atrophy in patients with multiple sclerosis treated with first- versus second-generation disease modifying therapy without clinical relapse.

BACKGROUND AND PURPOSE: The silent progression of patients with multiple sclerosis (MS) has been reported. The aim of this study was to investigate the association between brain atrophy rates and disease-modifying drugs (DMDs) in patients with MS during their relapse-free period. METHODS: Patients with relapsing-remitting MS were classified into two groups on the basis of clinical records, i.e. a first-generation DMD group treated with interferon-beta-1a, interferon-beta-1b or glatiramer acetate and a second-generation DMD group treated with dimethyl fumarate, fingolimod or natalizumab. Brain…

JCPyV NCCR analysis in PML patients with different risk factors: exploring common rearrangements as essential changes for neuropathogenesis.

BACKGROUND: During severe immunosuppression or treatment with specific biological drugs, human polyomavirus JC (JCPyV) may establish a lytic infection in oligodendrocytes, leading to progressive multifocal leukoencephalopathy (PML). Beyond AIDS, which represents the most common predisposing condition, several biological drugs have been associated to the development of PML, such as natalizumab, fingolimod and dimethyl fumarate, which have been showed to increase the risk of PML in the multiple sclerosis (MS) population. JCPyV non-coding control region (NCCR) can be found in two different forms:…

Общий синтез циклогельминтола I-IV свидетельствует о создании новой цистейно-селективной ковалентной реакционной группы.

Биосопоставимые кавалентные реактивные группы (КРГ) играют ключевую роль в ряде областей химической биологии и биологических наук, включая целевую ковалентную ингибиторную конструкцию и подготовку современных биологовых препаратов, таких, как антитела-наркотики. В этом исследовании мы представляем информацию о том, что небольшой хлорированный естественный продукт из поликетида циклогельминтиол II (CHM-II) действует в качестве нового типа CRG, предусматривающего как обратимую, так и необратимую реактивность. Мы разрабатываем первые синтезы из четырех простых циклогельминтолов, циклохелминтола I

Совпадение в аннотации оригинала
Biocompatible covalent reactive groups (CRGs) play pivotal roles in several areas of chemical biology and the life sciences, including targe … for CHM-II in cells with subsequent validation experiments demonstrating mechanistic similarity to dimethyl fumarate (DMF) - a known (covalent) drug used in the treatment of multiple sclerosis. Focused biochemical experiments revealed divergent thiol-reactivity inherent to the CHM-II scaffold and through further chemical derivatization of CHM-II we applied activit …

Оценка эффективности SARS-CoV-2 Дополнительные и ускорительные вакцины у пациентов с иммунокомпромиссным множественным склерозом: исследование COVACIMS.

Оценка исследований COVID-19 первичная вакцинация two Согласно сообщениям о тупых реакциях у пациентов с множественным склерозом (MS) anti-CD20 и sphingosine-1-phosphate (S1P) Модуторы. Была рекомендована расширенная первичная вакцинация (РВП) у пациентов с иммуноподверженным НР. Данные об эффективности ЭТС и последующей дозы ускорителя ограничены. Потенциальное когортное исследование (n = 270) была проведена оценка юморальности и клеточной иммуногенности схемы ЭВМ у пациентов с иммунокомпромиссным склерозом (т.е. anti-CD20, S1P модуляторы, натализумаб, терифлуномид или диметилфумарат) и регул

Совпадение в аннотации оригинала
Studies evaluating COVID-19 primary vaccination with two vaccines reported a blunt response in Multiple Sclerosis (MS) patients under anti-C … mpromised MS patients (i.e., treated with anti-CD20, S1P modulators, natalizumab, teriflunomide, or dimethyl fumarate) vs. regular primary vaccination in non-treated patients - primary course (PC) cohort. The effect of a subsequent booster dose was also assessed - first booster (FB) cohort . The seroconversion rates were 55% and 56% in anti-CD20 and 75% and 67% in …

Escalation to Anti-CD20 Treatment for Multiple Sclerosis Following Natalizumab-Associated Progressive Multifocal Leukoencephalopathy.

OBJECTIVES: Disease-modifying therapy (DMT) for multiple sclerosis (MS) after natalizumab-associated progressive multifocal leukoencephalopa … econstitution inflammatory syndrome before starting glatiramer acetate for DMT. She transitioned to dimethyl fumarate in 2013 after MS activity on MRI with negative CSF JC virus testing. Owing to worsening footdrop consistent with progression, she transitioned to ocrelizumab in 2017 and then to ofatumumab in 2020 due to logistics of medication administration. There …

The role of TH17 cells in multiple sclerosis: Therapeutic implications.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) where immunopathology is thought to be … ry T cells, which harbour the majority of peripheral TH17 cells, while the efficacy of natalizumab, dimethyl fumarate and importantly hematopoietic stem cell therapy correlates with TH17.1 cell inhibition. Interestingly, also CD20 antibodies target highly inflammatory TH cells and hamper TH17 differentiation by IL-6 reductions. Moreover, recovery rates of TH cells …

The glutathione-dependent neuroprotective activity of the blood-CSF barrier is inducible through the Nrf2 signaling pathway during postnatal development.

BACKGROUND: Choroid plexuses regulate the exchanges between the blood and the CSF, and provide trophic factors necessary to brain development. They also express detoxifying enzymes that protect the developing brain from harmful substances. Targeting the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway may enhance the detoxification capabilities of choroid plexuses that are linked to glutathione conjugation, but little is known about mechanisms of enzyme induction in this tissue. METHODS: Rat pups were treated with dimethylfumarate and the subcellular localization of Nrf2 w

[Current treatment of multiple sclerosis].

Multiple sclerosis (MS) is an autoimmune and degenerative disorder. In the past decades, the introduction of parenteral immunomodulatory therapies brought significant progress. These agents increase the number of relapses (shubs) by about 30%, and some of them has been shown to halter the accumulation of neurological symptoms and the development of disability. As first-line agents, interferon beta and glatiramer acetate (consisting of amino acids) can be used. Some new therapeutic strategies have been developed as a result of biotechnological development. The advantage of humanised monoclonal

Emerging strategies in drug repurposing for decreasing the risk of age-related macular degeneration.

INTRODUCTION: Vision loss in older adults is largely driven by age-related macular degeneration (AMD), characterized by progressive central … diabetic cohorts. Additional pharmacological agents include statins, glyburide, L-DOPA, fluoxetine, dimethyl fumarate, and nutraceuticals such as curcumin, melatonin, and N-acetylcysteine. EXPERT OPINION: Early AMD prevention through repurposed therapeutics, guided by AI-driven design and systems biology, may enable personalized care via multimodal risk stratifica …

Поглощение педиатрической склерозной популяции в Британской Колумбии, Канада, в результате изменения методов лечения.

ОБРАЩЕНИЕ: Лечение педиатрического множественных склерозов (POMS) развивается по мере того, как педиатрические клинические испытания проводятся для лечения заболеваний (DMT). Однако большинство ДМТ по-прежнему не имеют маркировки у детей, что создает препятствия для доступа и изменчивости методов лечения в различных юрисдикциях. Цель этого исследования заключалась в том, чтобы описать тенденции в области поглощения ДМТ в СУП в Британской Колумбии, Канада. МЕТОДЫ: Мы использовали взаимосвязанные клинические и административные наборы данных для выявления MS с началом <18 лет и для оценки поглоще

Совпадение в аннотации оригинала
BACKGROUND: The treatment of pediatric-onset multiple sclerosis (POMS) is evolving as disease-modifying therapies (DMTs) undergo pediatric c … ) did so at any age. Moderate-efficacy therapies (beta-interferons/glatiramer acetate/teriflunomide/dimethyl fumarate) were the initial DMT in 60 cases (79%) overall, however by the end of follow-up a high-efficacy therapy was the most recent DMT dispensed for 52/76 cases (68%). After 2016, anti-CD20 monoclonal antibodies became the most common DMT class dispensed. …

Oleic acid restores the impaired antitumor immunity of γδ-T cells induced by palmitic acid.

Dietary fatty acids (FAs) are associated with the therapeutic intervention under various health conditions. Human γδ-T cells are indispensab … or activity. Alternatively, direct blockade of IFNγ by anti-IFNγ mAb or inhibition of pyroptosis by dimethyl fumarate (DMF) also restores their antitumor activity. This study highlights a novel mechanism whereby dietary FAs modulate γδ-T cell function through regulating IFNγ-mediated pyroptosis. Additionally, it offers proof-of-concept for an innovative approach by …

PTSD symptoms among patients with multiple sclerosis in Jordan during October 7th Gaza war outbreak.

OBJECTIVE: Clinicians have noted that the ongoing war on Gaza has had a psychological impact on people with multiple sclerosis (PwMS) whose … gher risk were the unemployed (OR = 2.14, 95% CI = 1.13-4.07, P = 0.02), whereas patients receiving dimethyl fumarate (19.9%) were at lower risk (OR = 0.43, 95% CI = 0.19-0.94, P = 0.02). CONCLUSION: The high rate of significant PTSD symptoms among people with MS in this study underscores the need for attention by primary care providers and the implementation of a …

Oxaliplatin and 5-fluorouracil promote epithelial-mesenchymal transition via activation of KRAS/ERK/NF-κB pathway in KRAS-mutated colon cancer cells.

Oxaliplatin (L-OHP) and 5-fluorouracil (5-FU) are used to treat colon cancer; however, resistance contributes to poor prognosis. Epithelial- … tivation. Combined administration with KRAS siRNA, MEK1/2 inhibitor trametinib, and NF-κB inhibitor dimethyl fumarate (DMF), suppressed L-OHP- and 5-FU-induced EMT. These results suggest that KRAS/ERK/NF-κB pathway activation is important for EMT induction by L-OHP and 5-FU treatment. Thus, MEK1/2 and NF-κB inhibitors may facilitate the resistance acquisition to L- …