Результаты поиска

Реальный опыт использования озанимода у взрослых с множественной скlerозом.

AIM: Ozanimod — фингозин второго поколения. 1-phosphate Модулятор рецептора (S1PR), утвержденный для лечения повторного склероза (MS). Данные об использовании озанимодов в реальной клинической практике отсутствуют. Цель этого исследования состоит в том, чтобы определить характеристики людей, у которых MS (PwMS) предписан озанимод, а также стойкость, терпимость, безопасность и эффективность по отношению к ним. one Год. МЕТОДЫ: Ретроспективно собирались данные по взрослым с синдромом MS или клинически изолированным синдромом, которые получали озанимод two Высшие центры MS. Результаты: Мы определ

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… Bilateral macular edema was identified in one individual at 12 months of treatment with ozanimod; the treating clinician reported that co-morbid type 1 diabetes mellitus was likely contributory. One pwMS developed necrotizing fasciitis, which led to discontinuation of ozanimod. …

Pharyngeal-Esophageal Malignancies with Dermatologic Paraneoplastic Syndrome.

Systemic changes often send signals to the skin, and certain neoplastic diseases of the internal organs can also trigger skin manifestations. In this article, the authors make clinical photography presentations of the patients seen at our clinic with dermatologic paraneoplastic syndromes within pharyngeal-esophageal malignancies, describe several paraneoplastic dermatoses, and also review high-quality scientific literature in order to be able to highlight the dermatological signs of pharyngoesophageal malignant tumors. The majority of our patients with paraneoplastic dermatoses, filtering for

Interferon-Related Depression: A Primer on Mechanisms, Treatment, and Prevention of a Common Clinical Problem.

BACKGROUND: Depression is among the commonest of psychiatric disorders, and inflammatory mechanisms have been suggested to play a role in its pathophysiology. Interferons are a superfamily of proinflammatory cytokines that play a role in host defence mechanisms. Interferons are used in the treatment of a variety of autoimmune (e.g. multiple sclerosis), viral (e.g. chronic hepatitis B and C), and malignant (e.g. malignant melanoma, hairy cell leukemia) disorders; depression, however, is a notable and clinically troublesome adverse effect. OBJECTIVE: This article seeks to present a simple expla

Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma.

Continuous lenalidomide-dexamethasone (Rd)-based regimens are among the standards of care in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. The oral proteasome inhibitor ixazomib is suitable for continuous dosing, with predictable, manageable toxicities. In the double-blind, placebo-controlled TOURMALINE-MM2 trial, transplant-ineligible NDMM patients were randomized to ixazomib 4 mg (n = 351) or placebo (n = 354) plus Rd. After 18 cycles, dexamethasone was discontinued and treatment was continued using reduced-dose ixazomib (3 mg) and lenalidomide (10 mg) until progres

Adeno-associated virus as a delivery vector for gene therapy of human diseases.

Adeno-associated virus (AAV) has emerged as a pivotal delivery tool in clinical gene therapy owing to its minimal pathogenicity and ability to establish long-term gene expression in different tissues. Recombinant AAV (rAAV) has been engineered for enhanced specificity and developed as a tool for treating various diseases. However, as rAAV is being more widely used as a therapy, the increased demand has created challenges for the existing manufacturing methods. Seven rAAV-based gene therapy products have received regulatory approval, but there continue to be concerns about safely using high-dos

GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review.

Multiple myeloma is a genetically complex and heterogenous malignancy with a 5-year survival rate of approximately 60%. Despite advances in therapy, patients experience cycles of remission and relapse, with each successive line of therapy associated with poorer outcomes; therefore, therapies with different mechanisms of action against new myeloma antigens are needed. G protein-coupled receptor class C group 5 member D (GPRC5D) has emerged as a novel therapeutic target for the treatment of multiple myeloma. We review the biology and target validation of GPRC5D, and clinical data from early phas

Исследование in vitro токсикологических механизмов финолимода (S)-фосфата в камерах HEPG2.

Fingolimod (FTY720) — первый модератор рецептора фингозина-1-фосфата (S1P), утвержденный Администрацией продовольствия и лекарств США для лечения множественных склерозов. Активная форма FTY720 (S)-P действует в качестве мощного агониста рецептора S1P, что ведет к его нижнему регулированию на поверхности клеток, снижению активности и прекращению внутриклеточной сигнализации, зависимой от фингозина. Повышенные уровни фермента печени, клинически значимая травма печени и острая недостаточность печени наблюдались у пациентов, прошедших курс лечения с помощью FTY720 (S)-P, что требует дополнительног

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… FTY720 can also cause serious complications such as bradycardia, infections, macular edema. 12 An increase in liver enzymes has been observed in patients with MS who have been treated with FTY720. …

Сравнительная эффективность и терпимость Sphingosine-1-Phosphate Рецептор-модуляторы в пациентах с множественным склерозом: сетевая мета-анализа случайных контролируемых испытаний.

ИСТОРИЯ ВОПРОСА: Sphingosine-1-phosphate Рецепторные модуляторы (S1PRM) используются для лечения повторного множественных склерозов (MS). Каждый наркотик имеет разный S1PR-subtype избирательный подход. Они нацелены на G-протеиновые рецепторы, сцепленные с S1P, и оказывают значительное иммунодуляционное воздействие, например предотвращая появление новых CNS-повреждений и возобновление ранее существовавших повреждений. ЦЕЛЬ: Настоящее исследование направлено на изучение эффективности и безопасности S1PRM при обработке MS. МЕТОДЫ: В августе был проведен систематический поиск литературы в базах да

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… Its use is restricted, however, due to concerns with adverse effects such as decreased heart rate and atrioventricular block, increased risk of serious infections, macular edema or development of skin neoplasms. …

Acceptance of health technology assessment submissions with incremental cost-effectiveness ratios above the cost-effectiveness threshold.

ObjectivesIn health technology assessment (HTA) agencies where cost-effectiveness plays a role in decision-making, an incremental cost-effectiveness ratio (ICER) threshold is often used to inform reimbursement decisions. The acceptance of submissions with ICERs higher than the threshold was assessed across different agencies and across indications, in order to inform future reimbursement submissions.MethodsAll HTA appraisals from May 2000 to May 2014 from National Institute for Health and Care Excellence (NICE), Scottish Medicines Consortium (SMC), Pharmaceutical Benefits Advisory Committee (P

Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan.

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the "geriatric giants", including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation-or "inflammaging"-amplifies systemic decline. Key molecular pathwa

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… . | Diabetic macular edema, wet age-related macular degeneration. | Ongoing clinical trials, safety data limited. Avoid in patients with ocular infections. …

Быстрый обзор мер по улучшению ухода за людьми, страдающими множественным склерозом, диабетической ретинопатией и раком легких.

В Соединенных Штатах пациенты, страдающие хроническими заболеваниями, сталкиваются с различиями в показателях здоровья по всему спектру услуг по уходу. Среди пациентов с множественным склерозом, диабетической ретинопатией и раком легких не хватает доказательств, резюмирующих меры по улучшению ухода и сокращению этих различий. Цель этого оперативного обзора литературы заключалась в том, чтобы определить меры, принимаемые пациентами с такими хроническими заболеваниями в целях улучшения состояния здоровья и сокращения неравенства в плане выявления, диагностики, доступа к лечению и специалистам, с

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… Example MESH terms used in our search include “Multiple Sclerosis” [Mesh], “Lung Neoplasms” [Mesh], “Macular Edema” [Mesh], “Diabetic Retinopathy” [Mesh], “Medically Uninsured” [Mesh], and “Health Disparity, Minority and Vulnerable Populations” [Mesh]. …

Лимфопенсия, связанная с фингозином 1-phosphate Рецепторные модуляторы (S1PRM) в множестве склерозов: анализ европейских данных о фармакологической бдительности.

В течение последних нескольких десятилетий значительно возрос уровень лечения множественных склерозов (MS) благодаря внедрению методов коррекции заболеваний (ДМР). Финголимод, сипонимод, озанимод и понсимод относятся к новому поколению пероральных ДМТ, отнесенных к категории фингозина 1-phosphate Рецепторные модуляторы (S1PRM). Благодаря своему механизму действий они могут повысить риск лимфакопсии, которая может повлиять на терапевтическое управление людьми с НР. Цель этого исследования заключалась в том, чтобы описать и сопоставить частоту представления данных о лимфопопиях, связанных four S

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… According to their European Union Risk Management Plans, collective important identified and potential risks are bradyarrhythmia (including conduction defects and bradycardia complicated by hypotension) occurring post-first dose, liver transaminase elevation, macular edema, skin cancers (Basal cell carcinoma …

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immun

Antibody and aptamer-based therapies for osteoarthritis: Application of antibodies and promise of aptamers.

Osteoarthritis (OA) is a common degenerative inflammatory joint disease with progressive loss of articular cartilage that undermines patients' quality of life. There are no regulatory-approved, disease-modifying OA medications, despite a great deal of studies done to elucidate OA pathogenesis. Until now, OA pharmacological treatment focused mainly on generalized inhibition of inflammation and pain. Currently, monoclonal antibodies and nucleic-acid aptamers emerge as targeted therapies offering potential alternatives by addressing the complex challenges posed by OA, such as specifically reducin

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

Drug Repurposing Opportunities in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the deadliest tumors worldwide. The diagnosis is often possible only in the latter stages of the disease, with patients already presenting an advanced or metastatic tumor. It is also one of the cancers with poorest prognosis, presenting a five-year survival rate of around 5%. Treatment of PDAC is still a major challenge, with cytotoxic chemotherapy remaining the basis of systemic therapy. However, no major advances have been made recently, and therapeutic options are limited and highly toxic. Thus, novel therapeutic options are urgen

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… Other Relevant Examples Aflibercept is a VEGF inhibitor currently used to treat eye pathologies like neovascular age-related macular degeneration, diabetic macular edema and diabetic retinopathy [ 220 ]. …

Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence.

Conventional immunotherapy has emerged as a key option for cancer treatment. However, its efficacy has been limited in urological cancers, especially prostate cancer, because of the immunosuppressive tumor microenvironment (TME), difficulty in drug delivery, aberrant immune response, and damage to normal cells. Bispecific antibodies (BsAbs) are engineered proteins with two different antigen-binding domains, designed using different technologies and in various formats. BsAb-based tumor immunotherapy has yielded optimistic results in preclinical and clinical investigations of many tumor types, i

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… Faricimab, a CrossMab-based BsAb that targets ang-2 and VEGF, is currently FDA-approved for treating diabetic macular edema and nAMD 42 . The Orthogonal Fab interface, which introduces mutations into the variable region of Fab, allows the production of BsAbs in mammalian cells 31 , 49 . … Currently, over 200 BsAbs are being evaluated in clinical and preclinical trials, with nine already approved by the FDA for various conditions beyond cancer, including hemophilia A, macular degeneration, and diabetic macular edema. …

Skin-Directed Therapies in Mycosis Fungoides: An Update.

Mycosis fungoides (MF) is the most common subtype of cutaneous T cell lymphoma (CTCL), characterized by monoclonal proliferation of malignant T cells primarily involving the skin. The management of MF, especially in the early stages, involves skin-directed therapies (SDTs) to achieve disease control, alleviate symptoms, and enhance the quality of life (QoL). This review provides an updated overview of SDTs in MF treatment, including topical agents such as corticosteroids, retinoids, mechlorethamine, carmustine, imiquimod, as well as photodynamic therapy (PDT); phototherapy modalities including

Heyde Syndrome Unveiled: A Case Report with Current Literature Review and Molecular Insights.

Heyde syndrome, marked by aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome, is often underreported. Shear stress from a narrowed aortic valve degrades von Willebrand factor multimers, leading to angiodysplasia formation and von Willebrand factor deficiency. This case report aims to raise clinician awareness of Heyde syndrome, its complexity, and the need for a multidisciplinary approach. We present a 75-year-old man with aortic stenosis, gastrointestinal bleeding from angiodysplasia, and acquired von Willebrand syndrome type 2A. The patient w

Stevens–Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) : Immunologic Reactions

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