Aging Medicine最新文献

Immune checkpoint inhibitors (ICI), have transformed the management of several types of cancers; however, immune-related adverse events (irAEs) may cause treatment interruptions, chronic toxic effects, and death. Elderly patients are at high risk of cancer. Compared with traditional chemotherapy, immunotherapy has become a better alternative choice for elderly patients with cancer due to its high efficiency and low toxicity. However, the emergence of immunosenescence accompanied by advancing age raises safety concerns for ICI. Therefore, we summarize the characteristics of irAEs occurred in elderly patients with cancer and the physiological characteristics of immunosenescence, which will lay a theoretical foundation for the safety management of immunotherapy in elderly patients with cancer.

Insulin autoimmune syndrome (IAS) is a rare autoimmune disorder characterized by spontaneous hypoglycemia. The incidence of IAS is higher in East Asian populations compared to other populations. Delayed diagnosis and treatment can lead to recurrent hypoglycemia, significant glucose fluctuations, and adverse clinical outcomes, including life-threatening situations. Currently, no standardized guidelines exist for the diagnosis and treatment of IAS. This consensus aims to provide a systematic summary of the epidemiology, triggers, pathogenesis, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of IAS, with the objective of standardizing its clinical management.

The complex interplay between diamagnetic and paramagnetic substances within the brain, particularly in the context of Alzheimer's disease (AD), offers a rich landscape for investigation using advanced quantitative neuroimaging techniques. Although conventional approaches have focused on the paramagnetic properties of iron, emerging and promising research has highlighted the significance of diamagnetic signatures associated with beta-amyloid (Aβ) plaques and Tau (τ) protein aggregates. Quantitative susceptibility mapping (QSM) is a complex post-processing technique that visualizes and characterizes these subtle alterations in brain border tissue composition, such as the gray–white matter interface. Through voxel-wise separation of the contributions of diamagnetic and paramagnetic sources, QSM enabled the identification and quantification of Aβ and τ aggregates, even in the presence of iron. However, several challenges remain in utilizing diamagnetic signatures of Aβ and τ for clinical applications. These include the relatively small magnitude of the diamagnetic signal compared to paramagnetic iron, the need for high-resolution imaging and sophisticated analysis techniques, and the standardization of QSM acquisition and analysis protocols. Further research is necessary to refine QSM techniques, optimize acquisition parameters, and develop robust analysis pipelines to improve the sensitivity and specificity of detecting the diamagnetic nature of Aβ and τ aggregates. As our understanding of the diamagnetic properties of Aβ and τ continues to evolve, QSM is expected to play a pivotal role in advancing our knowledge of AD and other neurodegenerative diseases.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, characterized by mesangial IgA deposition. Asymptomatic hematuria with varying degrees of proteinuria is the most common clinical presentation, and 20%–40% of patients progress to end-stage kidney disease within 20 years after disease onset.¹ Currently, the “four-hit hypothesis” explains the pathogenesis of IgAN.² This hypothesis suggests that IgAN begins with elevated levels of circulating abnormally glycosylated galactose-deficient IgA1 (gd-IgA1), followed by the formation of immune complexes with anti-gd-IgA1 antibodies that ultimately deposit in the glomerular mesangium, leading to kidney injury. With the progressive studies of the pathogenesis of IgAN, key molecules in the pathogenesis have gradually become potential targets for future treatment strategies, and corresponding new drugs have been constantly emerging, as shown in Table 1. A proliferation inducing ligand (APRIL) is the 13th member of the TNF superfamily (TNFSF13), and as one of the growth factors of B cells, it can participate in the occurrence and development of IgAN by promoting B cell activation and the generation of gd-IgA1.³ The analysis of genome-wide association studies further suggests that TNFSF13 is a genome-wide locus significantly associated with IgAN, identifying the pathogenic signaling pathway and providing important evidence support for targeted drug development.⁴ Blocking APRIL activity is a potential therapeutic approach to reduce circulating levels of gd-IgA1 and its associated immune complexes.

The traditional treatment strategy of IgA nephropathy is mainly based on supportive treatment, combined with immunosuppressive therapy. In recent years, great progress has been made in the pathogenesis of IgA nephropathy, and put forward a new viewpoint on the treatment of IgA nephropathy. The new view is that the treatment needs to manage the two basic drivers of continuous nephron loss in IgAN at the same time. The focus of management in most patients should be to prevent or reduce IgA immune complex formation and immune complex-mediated glomerular injury. In parallel, manage the consequences of existing IgAN-induced nephron loss.

Sibeprenlimab (VIS649) is a humanized IgG2 monoclonal antibody that binds to and neutralizes the activity of APRIL. Blocking APRIL activity presents a potential method of treatment to reduce circulating levels of galactose-deficient IgA1 and associated immune complexes. The Phase II multicenter, double-blind, randomized, placebo-controlled trial of sibeprenlimab aims to evaluate the efficacy and safety of the drug in treating adult patients, who had biopsy-confirmed IgAN.¹⁶ Eligible patients with estimated glomerular filtration rate (eGFR) ≥30 mL per minute per 1.73 m² (as calculated with the use of the 20