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Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-Cd20 Monoclonal Antibodies for Multiple Sclerosis Treatment
No full textThe therapeutic scenario for Multiple Sclerosis (MS) has expanded rapidly over the last few years. Among the available treatments, anti-CD20 monoclonal antibodies, including rituximab, ocrelizumab, ofatumumab, and ublituximab, have shown significant results in reducing disease activity and slowing progression, particularly in relapsing MS. The distinct mechanisms of action, including the pharmacokinetic and pharmacodynamic profiles as well as the immunogenicity of these drugs, require careful consideration to tailor treatment for individual patients. A comprehensive review of the literature was conducted by searching PubMed and evaluating key studies, trials, and congress abstracts related to the use of anti-CD20 monoclonal antibodies. The analysis focused on the pharmacokinetic and pharmacodynamic profiles, as well as the immunogenicity, of anti-CD20 therapies currently available, with particular emphasis on the recently approved ublituximab. Ocrelizumab is effective in both relapsing-remitting and primary-progressive MS, using Antibody- Dependent Cellular Cytotoxicity (ADCC) as its primary mechanism of action, with intravenous and subcutaneous administration options ensuring flexible treatment delivery. Ofatumumab depletes B-cells through enhanced complement-dependent cytotoxicity, offering convenient monthly subcutaneous self-administration. Ublituximab's unique glycoengineered fragment crystallizable region enhances ADCC, resulting in rapid B-cell depletion and potentially improving its safety profile. Ublituximab allows for a shorter infusion time without requiring post-infusion monitoring after the second dose, provided there have been no prior reactions. Understanding the characteristics of different anti-CD20 monoclonal antibodies is critical for optimizing treatment, enhancing patient outcomes, and minimizing treatment burden. Ublituximab represents a promising option, offering a shorter infusion time and higher ADCC activity, which complements existing treatments such as ocrelizumab and ofatumumab
Striking the Right Chord at EJI: Introducing Editor-in-Chief Matteo Iannacone and the Seamless Transfer Policy
No full textImpact of extreme weather events on food security among older people: a systematic review
Get PDFBackground: Climate change has intensified the frequency and severity of extreme weather events, disproportionately affecting vulnerable populations, including older people for which the literature is still limited. This systematic review investigated the impact of extreme weather events on malnutrition and food security among individuals aged 60 and older. Methods: A systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted without restrictions (October 2024), and following PRISMA guidelines. Observational studies examining older adults exposed to extreme weather events (e.g., droughts, floods, heatwaves, hurricanes) and their effects on malnutrition or food security were included. The Newcastle-Ottawa Scale assessed study quality. Protocol was registered in PROSPERO (ID: CRD42024596910). Results: From 1,709 articles, six observational studies involving 265,000 participants (aged 60 years and over) were included. These studies spanned multiple geographies, with a concentration in the United States. Findings revealed a dual impact: while some studies reported protective factors, such as social support and economic stability, others highlighted increased malnutrition risk due to disrupted food supply, economic hardship, and inadequate adaptive responses. Heterogeneity in study designs, exposure definitions, and outcome measures limited comparability. Conclusion: Extreme weather events significantly impact malnutrition and food security among older adults, with outcomes influenced by socio-economic and geographical factors. Further longitudinal studies are needed to clarify causal pathways and inform targeted public health interventions to enhance resilience in aging populations
From classical approaches to artificial intelligence, old and new tools for PDAC risk stratification and prediction
No full textPancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal malignancies, characterized by late-stage diagnosis and limited therapeutic options. Risk stratification has traditionally been performed using epidemiological studies and genetic analyses, through which key risk factors, including smoking, diabetes, chronic pancreatitis, and inherited predispositions, have been identified. However, the multifactorial nature of PDAC has often been insufficiently addressed by these methods, leading to limited precision in individualized risk assessments. Advances in artificial intelligence (AI) have been proposed as a transformative approach, allowing the integration of diverse datasets—spanning genetic, clinical, lifestyle, and imaging data into dynamic models capable of uncovering novel interactions and risk profiles. In this review, the evolution of PDAC risk stratification is explored, with classical epidemiological frameworks compared to AI-driven methodologies. Genetic insights, including genome-wide association studies and polygenic risk scores, are discussed, alongside AI models such as machine learning, radiomics, and deep learning. Strengths and limitations of these approaches are evaluated, with challenges in clinical translation, such as data scarcity, model interpretability, and external validation, addressed. Finally, future directions are proposed for combining classical and AI-driven methodologies to develop scalable, personalized predictive tools for PDAC, with the goal of improving early detection and patient outcomes
Molecular constraints of sarcopenia in the ageing muscle
Get PDFSarcopenia, the age-related loss of skeletal muscle mass, strength, and function, is driven by a convergence of molecular, cellular, hormonal, nutritional, and neurological alterations. Skeletal muscle comprises multinucleated fibers supported by satellite cells-muscle stem cells essential for repair and regeneration. With age, both the structure and function of these components deteriorate: myonuclei become disorganized, gene expression skews toward catabolic, inflammatory, and fibrotic pathways, and satellite cell numbers and activity decline. Concurrently, mitochondrial dysfunction, impaired proteostasis, and vascular rarefaction limit energy availability and regenerative capacity. Neurodegeneration and age-related muscle fibers denervation further exacerbate muscle loss, particularly affecting fast-twitch fibers, and reduce motor unit integrity. These neural deficits, alongside changes at the neuromuscular junction, contribute to functional decline and diminished contractility. Hormonal changes-including reduced levels of growth hormone, testosterone, and IGF-1-undermine anabolic signaling and promote muscle atrophy. Nutritional factors are also pivotal: anorexia of aging and reduced dietary protein intake lead to suboptimal nutrient availability. Compounding this is anabolic resistance, a hallmark of aging muscle, in which higher levels of dietary protein and amino acids are required to stimulate muscle protein synthesis effectively. Physical inactivity and immobility, often secondary to chronic illness or frailty, further accelerate sarcopenia by promoting disuse atrophy. The molecular constraints of sarcopenia are deeply intertwined with non-molecular mechanisms-such as neuromuscular degeneration, hormonal shifts, inadequate nutrition, and reduced physical activity-creating a complex and self-reinforcing cycle that impairs muscle maintenance and regeneration in the elderly. This review synthesizes current evidence on these interconnected factors, highlighting opportunities for targeted interventions to preserve muscle health across the lifespan
Moving Toward Implementation of Responsible Artificial Intelligence in Health Care: The European TRAIN Initiative
No full textTiming of Cardiac Resynchronization Therapy Following Stable Medical Therapy in Patients With Heart Failure
No full textBackground: Guidelines' recommendations for cardiac resynchronization therapy (CRT) implantation in selected patients with heart failure (HF) exist. However, data on the best timing for CRT implantation after the achievement of stable medical therapy (SMT) and its association with outcomes are currently lacking. Objectives: The aim of this study was to investigate the timing of CRT implantation after the achievement of SMT, associated patient profiles, and clinical outcomes in a real-world HF population. Methods: Patients with HF treated with SMT derived from the Swedish ICD and Pacemaker Registry who received CRT between 2007 and 2020 were included in the study. Patient characteristics associated with a shorter or longer time to CRT implantation were assessed using multivariable logistic regression, and associations between the time from SMT to CRT implantation and clinical outcomes (mortality and morbidity) were analyzed using multivariable Cox regression. Results: Of the 9,409 patients, 43.8% received CRT at 6 months and ischemic heart disease were associated with a longer time. After adjustments, there was a 9% lower risk of cardiovascular death with a shorter time from SMT to CRT implantation of 9 months vs 3-9 months was associated with a 13% higher risk of cardiovascular death/HF hospitalization, a 12% higher risk of cardiovascular death (P = 0.040), and an 11% higher risk of first HF hospitalization (P = 0.013). Conclusions: Time from the achievement of SMT to CRT implantation decreased over the study period. Delayed CRT implantation beyond 3 months was associated with higher cardiovascular mortality compared with earlier implantation after GDMT optimization