ABSTRACT
BACKGROUND: Degenerative spondylolisthesis is a disease characterized by the displacement of a vertebra above the underlying vertebra. Lumbar arthrodesis is currently the most frequently performed surgical option for treatment due to the use of various approaches and techniques. The disease is characterized by low back pain, a clinical and public health problem, which in addition to having a socio-economic burden, severely affects functional status, quality of life (QoL), activity impairment, and health services. The study aims to investigate the benefits, in terms of pain, disability, andQoL, of lumbar arthrodesis surgery in patients with degenerative spondylolisthesis, at the latest follow-up. METHODS: A systematic literature review registered in PROSPERO (ID: CRD42022379242), was conducted in the databases of: Cochrane Library, PubMed, Embase, Scopus, and Web of Science. The key words used were as follows: "spondylolisthesis", "arthrodesis", "degenerative", "quality of life", "pain", "patient reported outcome", and "disability". RESULTS: A total of 26 articles were included. Significant differences were found between the preoperative and postoperative evaluation of the outcomes considered, in particular: pain (MD = -6.74; SD = 2.83; 95% CI: -8.01 to -5.46), low back pain (MD = -3.35; SD = 3.27; 95% CI: -3.61 to -3.10), lower limb pain (MD = -3.81; SD = 3.80; 95% CI: -4.10 to -3.51), disability (MD = -23.75; SD = 19.68; 95% CI: -25.26 to -22.23) and QoL (MD = 0.21; SD = 0.24; 95% CI: 0.19 to 0.23). CONCLUSIONS: The results show significant improvement in all measured variables, demonstrating that there are different surgical treatments to cure degenerative spondylolisthesis. However, residual pain impacting the QoL remains, regardless of the technique used. Therefore, the development of personalized pain management for patients with residual chronic pain is indicated.
ABSTRACT
The drivers of sporadic Alzheimer's disease (AD) remain incompletely understood. Utilizing directly converted induced neurons (iNs) from AD-patient-derived fibroblasts, we identified a metabolic switch to aerobic glycolysis in AD iNs. Pathological isoform switching of the glycolytic enzyme pyruvate kinase M (PKM) toward the cancer-associated PKM2 isoform conferred metabolic and transcriptional changes in AD iNs. These alterations occurred via PKM2's lack of metabolic activity and via nuclear translocation and association with STAT3 and HIF1α to promote neuronal fate loss and vulnerability. Chemical modulation of PKM2 prevented nuclear translocation, restored a mature neuronal metabolism, reversed AD-specific gene expression changes, and re-activated neuronal resilience against cell death.