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Reduced-versus Standard-dose Melphalan as Single-agent Conditioning Regimen in Auto HSCT for Multiple Myeloma: A Systematic Review and Meta-Analysis.

BackgroundThe optimal conditioning dose of melphalan for autologous hematopoietic stem cell transplantation (AHSCT) in multiple myeloma remains a subject of debate. While prior studies have presented conflicting evidence on whether standard-dose melphalan (SDM, 200 mg/m2) provides a statistically significant survival advantage over reduced-dose melphalan (RDM, 140 mg/m2), further investigation is necessary to clarify this.AimThis systematic review and meta-analysis aimed to consolidate existing studies and assess whether standard-dose melphalan confers a significant benefit in terms of overall

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… Autologous Hematopoietic Stem Cell Transplantation (AHSCT): Standard of Care for Relapsing-Remitting Multiple Sclerosis Patients. Neurol Ther. 2020; 9: 19-203. 8. Aypar E, İzzettin FV, Akı ŞZ, Sancar M, Yeğin Z, Türköz-Sucak G. …

BCMA/CD19 CAR T cell therapy for refractory myasthenia gravis: Proteomic signatures and single-cell transcriptomics of disease flares.

Myasthenia gravis (MG) is an autoimmune disorder characterized by B cell dysfunction. Here, we designed B cell maturation antigen (BCMA)/CD19 chimeric antigen receptor T cell (CAR T cell) therapy for six refractory MGs, demonstrating favorable safety with grade 1 cytokine release syndrome observed. CAR T cell expansion induced profound B cell depletion, a sustained reduction in acetylcholine receptor (AChR) antibody titers, and symptom improvement. Five patients achieved drug-free remission with minimal manifestations by month 6, persisting through the 12-month follow-up despite B cell reconst

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… Becher , B cell depletion attenuates CD27 signaling of T helper cells in multiple sclerosis . Cell Rep. Med. 5 , 101351 ( 2024 ). 38134930 10.1016/j.xcrm.2023.101351 PMC10829729 34 E. Ricker , M. Manni , D. Flores-Castro , D. Jenkins , S. Gupta , J. Rivera-Correa , W. Meng , A. M. Rosenfeld , T. … Somers , Age-associated B cells with proinflammatory characteristics are expanded in a proportion of multiple sclerosis patients . J. Immunol. 197 , 4576 – 4583 ( 2016 ). 27837111 10.4049/jimmunol.1502448 36 Y. Qin , M. L. Cai , H. Z. Jin , W. Huang , C. Zhu , A. Bozec , J. Huang , Z. …

Comparison of the prophylactic use of ibandronate and its use in early-stage osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: The aim of this study was to investigate the effects of ibandronate before and after the onset of osteonecrosis in rats with steroid-induced osteonecrosis of the femoral head. MATERIALS AND METHODS: A total of 24 female Sprague-Dawley rats were used in this study. Three groups were formed with eight rats in each group. The first group was the prophylactic group that received ibandronate treatment before and after the onset of osteonecrosis (Group PT). The second group received ibandronate treatment three weeks after the development of osteonecrosis (Group TAO). The third group was

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… In patients who will receive high-dose steroids (such as in the treatment of lymphoma or multiple sclerosis), starting with the intravenous form of bisphosphonates, which may show a more rapid effect, may preserve the trabecular bone architecture. …

A PRoliferation-Inducing Ligand (APRIL) in the Pathogenesis of Immunoglobulin A Nephropathy: A Review of the Evidence.

A PRoliferation-Inducing Ligand (APRIL), the thirteenth member of the tumor necrosis factor superfamily, plays a key role in the regulation of activated B cells, the survival of long-lived plasma cells, and immunoglobulin (Ig) isotype class switching. Several lines of evidence have implicated APRIL in the pathogenesis of IgA nephropathy (IgAN). Globally, IgAN is the most common primary glomerulonephritis, and it can progress to end-stage kidney disease; yet, disease-modifying treatments for this condition have historically been lacking. The preliminary data in ongoing clinical trials indicate

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… Fusion Protein Antagonists Targeting Both APRIL and BAFF Atacicept, a fusion protein comprising recombinant TACI and human IgG1, was originally developed for the treatment of immune-mediated disorders, including SLE and multiple sclerosis [ 119 ]. … Atacicept in multiple sclerosis (ATAMS): A randomised, placebo-controlled, double-blind, phase 2 trial. Lancet Neurol. 2014;13:353–363. doi: 10.1016/S1474-4422(14)70028-6. 122. Dhillon S. Telitacicept: First approval. Drugs. 2021;81:1671–1675. doi: 10.1007/s40265-021-01591-1. 123. …

Case report: A case of proliferative glomerulonephritis with monoclonal kappa-light chain deposits treated with daratumumab combination therapy.

INTRODUCTION: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a chronic glomerular disease caused by monoclonal gammopathy. IgG (mainly IgG3) is the most commonly involved isotype of PGNMID. Here we illustrated a novel medication regimen for the rare variant of PGNMID with deposition of monoclonal immunoglobulin light chain only (PGNMID-LC). Daratumumab has been proved effective in the treatment of plasma cell myeloma while its effect for PGNMID-LC has rarely been reported. METHODS: A daratumumab combination therapy (D-VCd regimen, specifically are daratum

Проверка и оценка применения Комплекса реабилитации МКФ: польская клиническая перспектива.

Проверка функционального статуса пациента в процессе реабилитации имеет важное значение для постоянного повышения качества предлагаемых реабилитационных услуг. Эта возможность обеспечивается за счет использования Международной классификации функционирования, инвалидности и здоровья (МКФ) и основных наборов МКФ, разработанных на ее основе. Цель этого исследования заключалась в том, чтобы подтвердить и оценить применение Комплекса реабилитации МКФ для реабилитационных пациентов в клинической практике в юго-восточной Польше. В исследовании использовалась польская версия справочника по рейтингам д

Dermatological manifestations of hematologic neoplasms. Part II: nonspecific skin lesions/paraneoplastic diseases.

Cutaneous manifestations occur in the course of hematologic malignancies and precede, accompany or occur late in relation to the diagnosis. They result from paraneoplastic phenomena, tumor infiltrations, immunosuppression resulting from the hematologic disease itself or its treatment. The dermatologist must be aware of these conditions that may be helpful both in the diagnosis of the underlying disease and in reducing patient morbidity. This review (part II) addresses the paraneoplastic dermatological changes associated with systemic hematologic malignancies.

Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.

Gene editing is a groundbreaking therapeutic approach that can potentially treat a broad spectrum of genetic and acquired diseases. This review highlights recent clinical trials employing advanced gene editing technologies such as CRISPR-Cas9, zinc-finger nucleases (ZFNs), and base editors across multiple disease areas including metabolic disorders, autoimmune diseases, muscular dystrophies, and inherited eye disorders. Central to the success of these therapies is the development of efficient and safe delivery systems, including lipid nanoparticles (LNPs), viral vectors (adenoviral and lentivi

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis.

The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current un

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… New insights into the role of chemokines and their receptors in these contexts are also informative for studies of brain inflammation caused by multiple sclerosis, Alzheimer’s or Parkinson’s disease. … Pathological expression of CXCL12 at the blood–brain barrier correlates with severity of multiple sclerosis. Am. J. Pathol. 172 799 – 808 10.2353/ajpath.2008.070918 18276777 PMC2258272 McDermott D. H. Liu Q. Ulrick J. Kwatemaa N. Anaya-O’Brien S. Penzak S. R. ( 2011 ). …

Biomimetic materials for medical applications.

AbstractRecent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases.

Комбинированная терапия резко поощряет воспоминание.

Множественный склероз (MS) — неизлечимое иммунное заболевание в центральной нервной системе, характеризующееся демиелинацией, аксонной дегенерацией и прогрессивной неврологической инвалидностью и до сих пор неизлечимое. Нынешние лекарства в основном предназначены для лечения иммунных заболеваний, но не предотвращают прогрессию заболеваний из-за их неспособности активно содействовать воссоединению. По сообщениям, небольшие молекулы способствуют регенерации миелина, но их терапевтическая эффективность ограничивается недостаточной иммунной модуляцией. Таким образом, стратегии, направленные как на

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Multiple sclerosis (MS) is an immune-mediated disease in the central nervous system that is characterized by demyelination, axonal degeneration, and progressive neurological disability and is so far incurable. Current medications are predominantly immune-targeted but fail to prevent disease progression due to their inability to actively promote remyelination…

Predicting Regulatory Product Approvals Using a Proposed Quantitative Version of FDA's Benefit-Risk Framework to Calculate Net-Benefit Score and Benefit-Risk Ratio.

BackgroundApproval of regulated medical products in the USA is based upon a rigorous review of the benefits and risks as performed by the US Food and Drug Administration (FDA) staff of scientists and is summarized in a descriptive and qualitative format called the FDA's Benefit-Risk Framework (BRF). This present method highlights the key factors in regulatory decision-making, but does not clearly define the reason for its final approval.MethodThis study proposes a quantitative version of FDA's BRF to calculate a Net-Benefit Score and a Benefit-Risk Ratio as a method to define a single-value su

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… Caster O Edwards IR Quantitative benefit–risk assessment of methylprednisolone in multiple sclerosis relapses BMC Neurol 2015 15 206 10.1186/s12883-015-0450-x 26475456 PMC4609048 5. …

Molecular and epigenetic regulatory mechanisms of normal stem cell radiosensitivity.

Ionizing radiation (IR) therapy is a major cancer treatment modality and an indispensable auxiliary treatment for primary and metastatic cancers, but invariably results in debilitating organ dysfunctions. IR-induced depletion of neural stem/progenitor cells in the subgranular zone of the dentate gyrus in the hippocampus where neurogenesis occurs is considered largely responsible for deficiencies such as learning, memory, and spatial information processing in patients subjected to cranial irradiation. Similarly, IR therapy-induced intestinal injuries such as diarrhea and malabsorption are commo

Current State and Future Challenges for PI3K Inhibitors in Cancer Therapy.

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… Notch activation contributes to the development of a variety of stem and early progenitor cells. 67 The defective Notch signaling is implicated in many cancers and diseases, including T-cell acute lymphoblastic leukemia, multiple sclerosis, melanoma, breast cancer, meningioma, lung adenocarcinoma, and … sclerosis | Atherosclerotic cardiovascular disease | Activation of Nrf2, Inhibition of NF-κB, agonism of HCAR2, inhibition of aerobic glycolysis, and depletion of GSH 9 | Fluoxetine 179 | Anti-depressant | Depression | Premenstrual dysphoria 10 | Minoxidil 180 | Antihypertensive vasodilator | Used as …

A Narrative Review of Osteonecrosis of the Jaw: What a Clinician Should Know.

Medication-related osteonecrosis of the jaw (MRONJ) is an uncommon complication of antiresorptive therapy (ART) in patients receiving higher and more frequent doses of osteoclast inhibitors. The jaws are the most common site, as they have high bone turnover. The oral structures are exposed to various types of stresses, like mastication and dental diseases, which lead to microtrauma and increased bone remodeling. The hallmark feature of MRONJ is the area of exposed, necrotic, nonhealing, asymptomatic bone for more than eight weeks. Objective signs are pain in the jaw and oral cavity, loose teet

Biomarkers in the diagnosis of lysosomal storage disorders: proteins, lipids, and inhibodies.

A biomarker is an analyte indicating the presence of a biological process linked to the clinical manifestations and outcome of a particular disease. In the case of lysosomal storage disorders (LSDs), primary and secondary accumulating metabolites or proteins specifically secreted by storage cells are good candidates for biomarkers. Clinical applications of biomarkers are found in improved diagnosis, monitoring disease progression, and assessing therapeutic correction. These are illustrated by reviewing the discovery and use of biomarkers for Gaucher disease and Fabry disease. In addition, rece

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… Plasma chitotriosidase activity is increased, albeit much more modestly, in several lysosomal and nonlysosomal diseases, such as sarcoidosis, visceral Leishmaniasis, leprosy, arthritis, multiple sclerosis, thalassemia, chronic obstructive pulmonary disease (COPD), malaria, and atherosclerosis (Hollak … sclerosis Brain 2006 129 517 526 16364958 10.1093/brain/awh707 Brady RO Kanfer JN Bradley RM Shapiro D Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease J Clin Invest 1966 45 1112 1115 5338605 10.1172/JCI105417 PMC292783 Brady RO Gal AE Bradley RM Martensson E …

Сексуальные отношения с лицами, страдающими расстройством бдительности: обзор.

Целью этого обзора повествования является проведение синтетического обзора современных знаний о взаимосвязи между расстройством гиперактивности (АДХД) и сексуальным функционированием взрослых с уделением особого внимания нейробиологическим механизмам, коморбидным расстройствам и воздействию фармакотерапии. Шесть независимых исследователей провели всеобъемлющий обзор литературы с использованием баз данных PubMed, Scopus и Google Scientist, охватывающих публикации, имеющиеся по состоянию на май 2024 года. Были включены первоначальные исследовательские документы, обзоры и метаанализы на английско

The pleiotropic effects of erythropoietin in infection and inflammation.

Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic

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… In experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, EPO inhibits pro-inflammatory responses of antigen-specific T cells and induces immune tolerance [35,36] . …

Кислотная терапия и риск излечения в случае воспламенительной болезни лопатки: сравнительное исследование в целях информирования о личностном лечении в мире.

Предыстория/цели: Известно, что ингибиторы протонных насосов (ИПЦ) изменяют состав кишечника микробиота; однако их связь с курсами заболеваний и результатами у пациентов с воспалительным кишечным заболеванием (ИБД) остается неопределенной. Наши цели заключались в оценке связи между использованием ИЦП и эскалацией лечения, диффицией Клостридиодов и использованием медицинских услуг в ИБД. Методы: Мы провели ретроспективное когортное исследование на платформе TriNetX. Пациенты IBD с ИЦП или histamine-2 Совпадали антагонисты рецептора (H2RA) one- чтобы...one с помощью баллов склонности. Итогом это