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Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.

BACKGROUND: CAR-T cell therapy represents a major breakthrough in hematological malignancies. However, the trade-off between insufficient treatment persistence and treatment-related toxicities (especially cytokine release syndrome, CRS) still limits its wider clinical application. MAIN BODY: Our review aims to reframe the understanding of this central dilemma. It posits that the dynamic imbalance of intracellular signaling networks and external inflammation in the tumor microenvironment (TME) are the causes of insufficient persistence of CAR-T cells and the severe CRS. The intracellular signa

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… The GLP-1 R agonist semaglutide and UrA inhibit mTOR and activate mitophagy, inducing metabolic reprogramming that enhances persistence [ 166 ]. Metformin modulates the ERK/CREB/PGC-1α signaling and balances STAT3 and STAT5 signaling. … Exemplifying this strategy, the combination of semaglutide and UrA enhances autophagy and mitophagy in CAR-T cells by inhibiting mTOR and activating Atg4b respectively, significantly improving CAR-T cell persistence and antitumor efficacy [ 166 ]. …

A brief clinical genetics review: stepwise diagnostic processes of a monogenic disorder-hypertriglyceridemia.

The completion of the Human Genome Project and tremendous advances in automated high-throughput genetic analysis technologies have enabled explosive progress in the field of genetics, which resulted in countless discoveries of novel genes and pathways. Many phenotype- or disease-associated single nucleotide polymorphisms (SNPs) with a high statistical significance have been identified through numerous genome-wide association studies (GWAS), and various polygenic risk scoring (PRS) schemes have been proposed to identify individuals with a high risk for a certain trait or disorder. Meanwhile, me

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… Although the FDA has approved GLP-1 agonists, such as semaglutide and liraglutide, in individuals older than 12 years old, the pros and cons of these agents should be discussed with a healthcare provider. …

European Association for the Study of Obesity Position Statement on the Diagnosis and Management of Obesity in Older Adults.

<p>Obesity is increasingly prevalent among older adults and is a major contributor to cardiometabolic diseases, functional decline, frailty, and loss of independence. The intersection between population ageing and the obesity epidemic poses major public health and clinical challenges. This European Association for the Study of Obesity (EASO) position statement represents an update of the EASO guideline from 2012, and provides a comprehensive overview of the epidemiology, pathophysiology, clinical consequences, and management of obesity in adults aged ≥65 years. It summarizes current evidence a

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… Three incretin mimetics (IMs) are currently approved for obesity pharmacotherapy: liraglutide and semaglutide, both GLP-1 receptor agonists, and tirzepatide, a dual GIP/GLP-1 receptor agonist. …

Advances in Extracellular Matrix-Associated Diagnostics and Therapeutics.

The extracellular matrix (ECM) is the common denominator of more than 50 chronic diseases. Some of these chronic pathologies lead to enhanced tissue formation and deposition, whereas others are associated with increased tissue degradation, and some exhibit a combination of both, leading to severe tissue alterations. To develop effective therapies for diseases affecting the lung, liver, kidney, skin, intestine, musculoskeletal system, heart, and solid tumors, we need to modulate the ECM's composition to restore its organization and function. Across diverse organ diseases, there are common denom

Cardiometabolic health in people with HIV: expert consensus review.

ObjectivesTo develop consensus data statements and clinical recommendations to provide guidance for improving cardiometabolic health outcomes in people with HIV based on the knowledge and experience of an international panel of experts.MethodsA targeted literature review including 281 conference presentations, peer-reviewed articles, and background references on cardiometabolic health in adults with HIV published between January 2016 and April 2022 was conducted and used to develop draft consensus data statements. Using a modified Delphi method, an international panel of 16 experts convened in

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… Healthcare; honoraria from Eli Lilly and Company, International Medical Press, Medscape, Novo Nordisk and ViiV Healthcare; travel support from Novo Nordisk (paid to institution); participation on data safety monitoring boards/advisory boards for Eli Lilly and Company, Novo Nordisk and Pfizer; receipt of semaglutide …

Post-marketing safety of tarlatamab in small cell lung cancer based on FAERS and WHO-VigiAccess with SHAP-based interpretable machine learning analysis of immune-related adverse events.

BACKGROUND: Tarlatamab is a DLL3-targeted bispecific T-cell engager approved for previously treated extensive-stage small cell lung cancer (ES-SCLC). However, its post-marketing safety profile in routine practice remains incompletely characterized. METHODS: We conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System from Q2 2024 to Q3 2025, with a descriptive cross-database comparison using WHO-VigiAccess. Disproportionality analyses were performed using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, an

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Abstracts From the 42nd Annual Scientific Meeting of the Transplantation Society of Australia and New Zealand held on June 16-18, 2024

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… Recruited patients were commenced on 1mg subcutaneous semaglutide weekly, and demographic data, cardiac function, and transplant listing status were evaluated pre- and post-GLP-1 RA use. … Results : Nine patients (100% male, mean age: 54.5 ± 8.2 years) with ESHF (mean LVEF: 19.4 ± 0.1%) and severe obesity (mean pre-GLP-1 RA BMI: 36.3 ± 3.4 kg/m 2 ) were prescribed semaglutide for a mean duration of 5 months (range: 1 – 16 months). …

Heart Failure in Older Patients: An Update.

Heart failure (HF) is a clinical syndrome with high incidence and prevalence and high morbidity and death rate, even in the short term, representing a serious public health issue, mainly in older people. It is a growing cause for hospital admission in this age group, being frequently associated with several comorbidities, further aggravating the disease's course. Moreover, older HF patients are usually affected by clinical conditions, like frailty, malnutrition, and cachexia, which significantly impact the overall management of HF and need to be properly identified and treated. Diagnosing and

An Updated Comprehensive Review on Diseases Associated with Nephrotic Syndromes.

There have been exciting advances in our knowledge of primary glomerular diseases and nephrotic syndromes in recent years. Beyond the histological pattern from renal biopsy, more precise phenotyping of the diseases and the use of modern nephrogenetics helps to improve treatment decisions and sometimes also avoid unnecessary exposure to potentially toxic immunosuppression. New biomarkers have led to easier and more accurate diagnoses and more targeted therapeutic decisions. The treatment landscape is becoming wider with a pipeline of promising new therapeutic agents with more sophisticated appr

Role of mitochondria in physiological activities, diseases, and therapy.

Mitochondria are generally considered essential for life in eukaryotic organisms because they produce most of the energy or adenosine triphosphate (ATP) needed by the cell. Beyond energy production, it is now widely accepted that mitochondria also play a pivotal role in maintaining cellular homeostasis and signaling. The two core processes of mitochondrial dynamics, fission and fusion, serve as crucial foundations for maintaining mitochondrial morphology, distribution, and quantity, thereby ensuring cellular homeostasis. Mitochondrial autophagy (mitophagy) ensures the selective degradation of

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… Idebenone Phase IV ATP production modulator and antioxidant NCT05987397 Diabetes mellitus Acipimox Phase III Antioxidant NCT01816165 Sodium-phenylbutyrate Phase IV Accelerate branched-chain amino acids oxidation NCT05836350 Dapagliflozin Phase IV Sodium-glucose cotransporter 2 inhibitor NCT03919656 Semaglutide … production modulator and antioxidant | NCT05987397 Diabetes mellitus | Acipimox | Phase III | Antioxidant | NCT01816165 | Sodium-phenylbutyrate | Phase IV | Accelerate branched-chain amino acids oxidation | NCT05836350 | Dapagliflozin | Phase IV | Sodium-glucose cotransporter 2 inhibitor | NCT03919656 | Semaglutide …

Unraveling Obesity and Multiple Myeloma: Insights from Epidemiology and Molecular Mechanisms.

Purpose of reviewThe global incidence of obesity has risen dramatically in recent decades, with consequent detrimental health effects. Extensive studies have demonstrated that obesity significantly affects the risk, prognosis, and progression of various cancers, including multiple myeloma (MM). As an established modifiable risk factor for both MM and its precursor stages -monoclonal gammopathy of unknown significance (MGUS) and smoldering MM (SMM)- the association between obesity and disease onset has become a compelling area of research. This review presents a comprehensive overview of the cu

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… Glucagon-like Peptide-1 Receptor Agonists Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), such as liraglutide and semaglutide, have emerged as a groundbreaking class of medications in the management of obesity. …

Endothelial dysfunction in congenital adrenal hyperplasia due to 21-hydroxylase deficiency: current knowledge and novel biomarkers.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a complex endocrine disorder characterized by impaired cortisol synthesis and androgen excess. Beyond its hormonal and metabolic implications, CAH has been increasingly associated with an elevated risk of cardiovascular complications, including endothelial dysfunction, a critical precursor to atherosclerosis and a risk factor for cardiovascular and metabolic diseases. This review explores the current knowledge on endothelial function in patients with CAH, focusing on the interplay between chronic hormonal imbalanc

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… Newer antiobesity medications (liraglutide, semaglutide, tirzepatide, and naltrexone/bupropion) have not yet been studied in patients with CAH. …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Abstract

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… Hospital- Catanzaro Italy, 2 La Sapienza University- Roma, Italy Introduction: Cardiovascular outcome trials (CVOTs) demonstrated that GLP1-RAs have effectively reduced CV risk in T2DM patients, so their use is recommended by guidelines Aim: The objective of our work is to evaluate the effect of Semaglutide … Conclusion: Our results demonstrated that 6 months treatment with Semaglutide, improved GLS, GLS endo-epi ratio and GWE, due to reduced levels of oxidative stress, platelet activation, probably acting on the microcirculation. …

Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

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… Ryan, D. (2021) Next Generation Antiobesity Medications: Setmelanotide, Semaglutide, Tirzepatide and Bimagrumab: What do They Mean for Clinical Practice? Journal of Obesity & Metabolic Syndrome , 30(3), pp.196-208. …

Position Statement on Multimodal Cardiac Imaging in Patients with Systemic Diseases - 2026.

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Clinical Practice Guidelines for Menopause: An Executive Summary and Recommendations: Indian Menopause Society 2026.

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Oral Presentations

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ePoster.

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