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Gene Therapy Approach for Intervertebral Disc Degeneration: An Update
Yoshiki Takeoka,Takashi Yurube,Kotaro Nishida 대한척추신경외과학회 2020 Neurospine Vol.17 No.1
Intervertebral disc degeneration is the primary cause of back pain and associated with neurological disorders including radiculopathy, myelopathy, and paralysis. The currently available surgical treatments predominantly include the excision of pathological discs, resulting in the function loss, immobilization, and potential additional complications due to the altered biomechanics. Gene therapy approach involves gene transfer into cells, affects RNA and protein synthesis of the encoded genes in the recipient cells, and facilitates biological treatment. Relatively long-exerting therapeutic effects by gene therapy are potentially advantageous to treat slow progressive degenerative disc disease. In gene therapy, the delivery method and selection of target gene(s) are essential. Although gene therapy was first mediated by viral vectors, technological progress has enabled to apply nonviral vectors and polyplex micelles for the disc. While RNA interference successfully provides specific downregulation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc degeneration. Then, more recent findings of our studies have suggested autophagy, the intracellular self-digestion, and recycling system under the negative regulation by the mammalian target of rapamycin (mTOR), as a gene therapy target in the disc. Here we briefly review backgrounds and applications of gene therapy for the disc, introducing strategies of autophagy and mTOR signaling modulation through selective RNA interference.
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Takahiro Niikura,Sang Yang Lee,Yoshitada Sakai,Kotaro Nishida,Ryosuke Kuroda,Masahiro Kurosaka 대한정형외과학회 2014 Clinics in Orthopedic Surgery Vol.6 No.2
Background: Currently, an algorithmic approach for deciding treatment options according to the Vancouver classification is widely used for treatment of periprosthetic femoral fractures after hip arthroplasty. However, this treatment algorithm based on the Vancouver classification lacks consideration of patient physiology and surgeon’s experience (judgment), which are also important for deciding treatment options. The purpose of this study was to assess the treatment results and discuss the treatment options using a case series. Methods: Eighteen consecutive cases with periprosthetic femoral fractures after total hip arthroplasty and hemiarthroplasty were retrospectively reviewed. A locking compression plate system was used for osteosynthesis during the study period. The fracture type was determined by the Vancouver classification. The treatment algorithm based on the Vancouver classification was generally applied, but was modified in some cases according to the surgeon’s judgment. The reasons for modification of the treatment algorithm were investigated. Mobility status, ambulatory status, and social status were assessed before the fracture and at the latest follow-up. Radiological results including bony union and stem stability were also evaluated. Results: Thirteen cases were treated by osteosynthesis, two by revision arthroplasty and three by conservative treatment. Four cases of type B2 fractures with a loose stem, in which revision arthroplasty is recommended according to the Vancouver classification, were treated by other options. Of these, three were treated by osteosynthesis and one was treated conservatively. The reasons why the three cases were treated by osteosynthesis were technical difficulty associated with performance of revision arthroplasty owing to severe central migration of an Austin-Moore implant in one case and subsequent severe hip contracture and low activity in two cases. The reasons for the conservative treatment in the remaining case were low activity, low-grade pain, previous wiring around the fracture and light weight. All patients obtained primary bony union and almost fully regained their prior activities. Conclusions: We suggest reaching a decision regarding treatment methods of periprosthetic femoral fractures by following the algorithmic approach of the Vancouver classification in addition to the assessment of each patient’s hip joint pathology, physical status and activity, especially for type B2 fractures. The customized treatments demonstrated favorable overall results.
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