European journal of clinical investigation
-
Eur. J. Clin. Invest. · Nov 2024
Association between insulin-associated gene polymorphisms and new-onset diabetes mellitus in statin-treated patients.
While statins are effective at managing lipid levels, there is growing evidence for new-onset diabetes mellitus (NODM). The insulin signalling pathway (ISP) inhibited by statins is one of the potential mechanisms; however, most studies have been limited to in vitro settings. Therefore, this study aimed to identify the genetic associations within the ISP-related genes and NODM. ⋯ This study revealed the ISP-related genetic effects, specifically involving genes such as INSR, IGF1R and PIK3R1, in the development of statin-induced NODM. Our findings suggest a potential mechanism of statin-induced NODM related to ISP-related genetic variants.
-
Eur. J. Clin. Invest. · Nov 2024
ReviewCirculating Fetuin-A concentrations in rheumatic diseases: a systematic review and meta-analysis.
Rheumatic diseases (RDs) include a broad group of disabling conditions with different phenotypes, from autoimmune to autoinflammatory, degenerative, metabolic or mixed manifestations. With the continuous efforts to identify therapeutic targets for new biologic drugs to treat overt clinical manifestations, research is also focusing on the discovery of new biomarkers to diagnose and manage early disease stages. In this context, we conducted a systematic review and meta-analysis of Fetuin-A (FtA), a glycoprotein synthesized by the liver that participates in several biological processes and has been proposed as a biomarker for several disorders, including rheumatoid arthritis. ⋯ In conclusion, our study identified significant reductions in FtA concentrations in RD patients versus healthy controls. These alterations were significantly associated with specific study and patient characteristics. Further research is required to identify the exact pathophysiological mechanisms underlying these alterations and the possible utility of measuring FtA for the diagnosis and management of RDs.
-
Eur. J. Clin. Invest. · Nov 2024
Genome-wide methylation profiling of maternal cell-free DNA using methylated DNA sequencing (MeD-seq) indicates a placental and immune-cell signature.
Placental-originated cell-free DNA (cfDNA) provides unique opportunities to study (epi)genetic placental programming remotely, but studies investigating the cfDNA methylome are scarce and usually technologically challenging. Methylated DNA sequencing (MeD-seq) is well compatible with low cfDNA concentrations and has a high genome-wide coverage. We therefore aim to investigate the feasibility of genome-wide methylation profiling of first trimester maternal cfDNA using MeD-seq, by identifying placental-specific methylation marks in cfDNA. ⋯ MeD-seq can detect (novel) genome-wide placental DNA methylation marks and determine fetal sex in maternal cfDNA. Our results indicate a placental and immune-cell contribution to the pregnancy-specific cfDNA methylation signature. This study supports future research into maternal cfDNA methylation.
-
Eur. J. Clin. Invest. · Nov 2024
Ceramide and phosphatidylcholine lipids-based risk score predicts major cardiovascular outcomes in patients with heart failure.
Ceramide and phosphatidylcholine lipids-based risk score (CERT2) has shown a strong prognostic value in predicting cardiovascular (CV) events in patients with ischemic heart disease. This study aimed to investigate the prognostic value of CERT2 risk score in patients with heart failure (HF). ⋯ The CERT2 risk score is strongly associated with an increased risk of CV death, all-cause death and MACE in patients with HF.
-
Eur. J. Clin. Invest. · Nov 2024
Review[225Ac]Ac-PSMA for the treatment of metastatic castration-resistant prostate cancer: A systematic review and meta-analysis.
Approximately 10%-20% of prostate cancers progress to metastatic and castration-resistant forms (mCRPC). Radioligand (RLT) therapy with [177Lu]Lu-prostate-specific membrane antigen (PSMA) is an approved treatment for metastasized mCRPC. Moreover, Actinium-225 (225Ac), an alpha-emitter isotope, has also been used to label PSMA and, recently, to treat mCRPC patients with encouraging results. However, robust clinical data on [225Ac]Ac-PSMA therapy and its comparison with [177Lu]Lu-PSMA are still limited. Our aim was to evaluate the role of [225Ac]Ac-PSMA in treating mCRPC and compare it with conventional [177Lu]Lu-PSMA therapy. ⋯ Overall, the main results of our study showed that [225Ac]Ac-PSMA-617 had a significant therapeutic effect on mCRPC with an acceptable toxicity level. The latter, however, appears greater than with [177Lu]Lu-PSMA-617. In future studies, an adequate analysis of the incidence of side effects associated with [225Ac]Ac-PSMA should be performed to evaluate the role of cumulative toxicity of earlier treatments and the higher frailty of heavily pretreated patients.