Feifei Zhou, Shuyang Li, Yanbin Zhao, Yilong Zhang, Kevin L. Ju, Fengshan Zhang, Shengfa Pan and Yu Sun
The authors aimed to identify factors that may be useful for quantifying the amount of degenerative change in preoperative patients to identify ideal candidates for cervical disc replacement (CDR) in patients with a minimum of 10 years of follow-up data.
During the period from December 2003 to August 2008, 54 patients underwent CDR with a Bryan cervical disc prosthesis performed by the same group of surgeons, and all of the patients in this group with at least 10 years of follow-up data were enrolled in this retrospective analysis of cases. Postoperative bone formation was graded in radiographic images by using the McAfee classification for heterotopic ossification. Preoperative degeneration was evaluated in radiographs based on a quantitative scoring system. After univariate analysis, the authors performed multifactor logistic regression analysis to identify significant factors. To determine the cutoff points for the significant factors, a receiver operating characteristic (ROC) curve analysis was conducted.
Study patients had a mean age of 43.6 years and an average follow-up period of 120.3 months. The patients as a group had a 68.2% overall incidence of bone formation. Based on univariate analysis results, data for patient sex, disc height, and the presence of anterior osteophytes and endplate sclerosis were included in the multivariate analysis. According to the analysis results, the identified independent risk factors for postoperative bone formation included disc height, the presence of anterior osteophytes, and endplate sclerosis, and according to a quantitative scoring system for degeneration of the cervical spine based on these variables, the ROC curve indicated that the optimal cutoff scores for these risk factors were 0.5, 1.5, and 1.5, respectively.
Among the patients who were followed up for at least 10 years after CDR, the incidence of postoperative bone formation was relatively high. The study results indicate that the degree of degeneration in the target level before surgery has a positive correlation with the incidence of postoperative ossification. Rigorous indication criteria for postoperative ossification should be applied in patients for whom CDR may be a treatment option.
Fengshan Yu, Zhifei Wang, Mikiei Tanaka, Chi-Tso Chiu, Peter Leeds, Yumin Zhang and De-Maw Chuang
Although traumatic brain injury (TBI) is the leading cause of death and morbidity in young adults, no effective pharmaceutical treatment is available. By inhibiting glycogen synthase kinase–3 (GSK-3) and histone deacetylases (HDACs), respectively, lithium and valproate (VPA) have beneficial effects in diverse neurodegenerative diseases. Furthermore, in an excitotoxic neuronal model and in animal models of amyotrophic lateral sclerosis, Huntington disease, and stroke, combined treatment with lithium and VPA produces more robust neuroprotective effects than treatment with either agent alone. Building on previous work that establishes that therapeutic doses of either lithium or VPA have beneficial effects in mouse models of TBI, this study evaluated the effects of combined treatment with subeffective doses of lithium and VPA in a mouse model of TBI.
Male C57BL/6 mice underwent TBI and were subsequently treated with lithium, VPA, or a combination of lithium and VPA 15 minutes post-TBI and once daily thereafter for up to 3 weeks; all doses were subeffective (1 mEq/kg of lithium and 200 mg/kg of VPA). Assessed parameters included lesion volume via H & E staining; blood-brain barrier (BBB) integrity via immunoglobulin G extravasation; neurodegeneration via Fluoro-Jade B staining; motor coordination via a beam-walk test; and protein levels of acetylhistone H3, phospho-GSK-3β, and β-catenin via Western blotting.
Posttrauma treatment with combined subeffective doses of lithium and VPA significantly reduced lesion volume, attenuated BBB disruption, and mitigated hippocampal neurodegeneration 3 days after TBI. As expected, subeffective doses of lithium or VPA alone did not have these beneficial effects. Combined treatment also improved motor coordination starting from Day 7 and persisting at least 21 days after TBI. Acetylation of histone H3, an index of HDAC inhibition, was robustly increased by the combined treatment 3 days after TBI.
Cotreatment with subeffective doses of lithium and VPA significantly attenuated TBI-induced brain lesion, BBB disruption, and neurodegeneration, and robustly improved long-term functional recovery. These findings suggest that potentiating histone acetylation by HDAC inhibition is probably part of the mechanism underlying the beneficial effects associated with this combined treatment for TBI. Because both lithium and VPA have a long history of safe clinical use, the results suggest that using a combination of these 2 agents at subtherapeutic doses to treat patients with TBI may also reduce side effects and enhance tolerability.