ABSTRACT
Objectives: To formulate the most current, evidence-based recommendations for the role of medication, physical medicine, and rehabilitation in the management of acute low back pain lasting <4 weeks. Methods: A systematic literature search in PubMed and Google Scholar databases was performed from 2012 to 2022 using the search terms "acute low back pain," "drugs," "bed rest," "physical medicine," rehabilitation." Standardized screening criteria resulted in a total of 39 articles that were analyzed, including 16 RCTs, 8 prospective studies, 6 retrospective studies, and 9 systematic reviews. This up-to-date information was reviewed and presented at two separate meetings of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. Two rounds of the Delphi method were utilized to vote on the statements and arrive at a positive or negative consensus. Results and conclusion: The WFNS Spine Committee finalized twelve recommendation guidelines on the role of medication, physical medicine and rehabilitation in the management of acute LBP. We advocate for a uniform approach to the treatment of these patients, including proper patient education and utilizing drugs with proven efficacy and minimal side effects. First-line pharmacologic agents are acetaminophen and NSAIDs; muscle relaxants can be used for spasms and pain reduction, and opioids should be minimized. Continued activity, rather than bed rest, is recommended, and lumbar spine orthotics may be used to reduce pain and augment functional status. Thermotherapy, cryotherapy, TENs, spinal manipulative therapy, and acupuncture may all be used as adjuncts to improve acute LBP.
ABSTRACT
Glioblastoma Multiforme (GBM) is the most invasive and prevalent Central Nervous System (CNS) malignancy. It is characterised by diffuse infiltrative growth and metabolic dysregulation that impairs the extent of surgical resection (EoR), contributing to its poor prognosis. 5-Aminolevulinic acid (5-ALA) fluorescence-guided surgical resection (FGR) takes advantage of the preferential generation of 5-ALA-derived fluorescence signal in glioma cells, thereby improving visualisation and enhancing the EoR. However, despite 5-ALA FGR is a widely used technique in the surgical management of malignant gliomas, the infiltrative tumour margins usually show only vague or no visible fluorescence and thus a significant amount of residual tumour tissue may hence remain in the resection cavity, subsequently driving tumour recurrence. To investigate the molecular mechanisms that govern the preferential accumulation of 5-ALA in glioma cells, we investigated the precise subcellular localisation of 5-ALA signal using Correlative Light and Electron Microscopy (CLEM) and colocalisation analyses in U118MG glioma cells. Our results revealed strong 5-ALA signal localisation in the autophagy compartment - specifically autolysosomes and lysosomes. Flow cytometry was employed to investigate whether autophagy enhancement through spermidine treatment (SPD) or nutrient deprivation/caloric restriction (CR) would enhance 5-ALA fluorescence signal generation. Indeed, SPD, CR and a combination of SPD/CR treatment significantly increased 5-ALA signal intensity, with a most robust increase in signal intensity observed in the combination treatment of SPD/CR. When using 3-D glioma spheroids to assess the effect of 5-ALA on cellular ultrastructure, we demonstrate that 5-ALA exposure leads to cytoplasmic disruption, vacuolarisation and large-scale mitophagy induction. These findings not only suggest a critical role for the autophagy compartment in 5-ALA engagement and signal generation but also point towards a novel and practically feasible approach to enhance 5-ALA fluorescence signal intensity. The findings may highlight that indeed autophagy control may serve as a promising avenue to promote an improved resection and GBM prognosis.
