Annals of the Academy of Medicine, Singapore最新文献

Introduction: Sepsis-induced myopathy (SIM) is a severe complication contributing to long-term morbidity and mortality in sepsis survivors. Emerging evidence highlights the role of pyroptosis in SIM pathogenesis. This study aims to identify pyroptosis-related genes and potential pharmacological targets for SIM and explore their therapeutic implications.

Method: The GSE13205 dataset from the Gene Expression Omnibus database was analysed to identify differentially expressed pyroptosis-related genes in SIM. Gene Set Variation Analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the biological functions and associated pathways. Hub genes were identified through protein-protein interaction network analysis. The Connectivity Map (CMap) database was used to predict candidate therapeutic compounds targeting these genes.

Results: A total of 39 pyroptosis-related genes were identified as differentially expressed in SIM. These genes were primarily associated with apoptosis, regulation of cell death, p53 signalling, circadian rhythm and responses to hypoxia and chemical stress. KEGG pathway analysis revealed enrichment in apoptosis, p53 signalling, microRNA in cancer and endocrine resistance pathways. Ten potential therapeutic compounds were predicted via CMap based on hub gene profiles. However, experimental validation of these compounds in the context of SIM is needed to assess their therapeutic efficacy.

Conclusion: This study identifies key pyroptosis-related genes and potential therapeutic compounds for SIM, providing new insights into its molecular mechanisms and suggesting novel strategies for treatment. Further experimental validation is required to confirm the clinical relevance and therapeutic potential of these findings.

Introduction: The authors aim to determine tuberculosis (TB) incidence and ascertain risk factors for TB in patients with stage 5 chronic kidney disease (CKD5) in the Singapore population.

Method: A retrospective cohort study of all stage CKD5 patients registered in Singapore's renal registry who developed active pulmonary and extra-pulmonary TB between 2012 and 2021, after their CKD5 diagnosis.

Results: TB incidence among CKD5 patients was significantly higher compared to the general Singapore population, ranging from 279 to 630 per 100,000 CKD5 population over the period from 2012 to 2021, versus 32.6 to 41.1 per 100,000 general population during the same period. In univariable comparisons, statistically significant risk factors for development of TB disease in CKD5 patients were: male sex (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.3-2.12, P<0.001), Malay ethnicity (OR 1.33, 95% CI 1.02-1.72, P=0.03) and reported history of "ever smoking" (OR 2.93, 95% CI 2.15-4.03, P<0.001). CKD5 patients who were on any type of dialysis were also observed to have a significantly higher risk of developing TB disease, haemodialysis (OR 2.31, 95% CI 1.69-3.23, P<0.001), peritoneal dialysis (OR 2.53, 95% CI 1.46-4.23, P=0.001) or a combination of haemodialysis and peritoneal dialysis (OR 2.55, 95% CI 1.63-3.95, P<0.001), compared to those who had not been initiated on dialysis. These factors remained significant in the multivariable models except ethnicity.

Conclusion: CKD5 patients have an increased risk of developing TB, particularly when certain risk factors are present, such as male sex or receiving dialysis. Clinicians should maintain a high degree of suspicion for TB in CKD5 patients with compatible clinical symptoms.