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Background Context
The concept of dynamic stabilization (DS) of the lumbar spine for treatment of degenerative instability has been introduced almost two decades ago. Dynamic stabilization follows the principle of controlling movement in the coronal plane by providing load transfer of the spinal segment without fusion and, at the same time, reducing side effects such as adjacent segment disease (ASD). So far, only little is known about revision rates after DS due to ASD and screw loosening (SL).Purpose
The present study aimed to evaluate the longitudinal revision rates following dynamic pedicle screw stabilization in the lumbar spine and to determine specific risk factors predictive for ASD, SL, and overall reoperation in a large cohort with considerable follow-up.Design
We carried out a post hoc analysis of a prospectively collected database in a level I spine center.Patients Example
The patient sample comprised 283 (151 female/132 male) consecutive patients suffering from painful degenerative lumbar segmental instability with or without spinal stenosis who underwent DS of the lumbar spine (Ulrich Cosmic, Ulrich Medical, Ulm, Germany) between January 2008 and December 2011.Outcome Measures
Longitudinal reoperation rate and risk factors predictive for revision surgery were evaluated.Methods
We analyzed the longitudinal reoperation rate due to ASD and SL and overall reoperation. Risk factors such as age, gender, body mass index, lumbar lordosis (LL), number of segments, and number of previous surgeries were taken into account. Regular and mixed model logistic regressions were performed to determine risk factors for revision surgery on a patient and on a screw level.Results
The mean age was 65.7±10.2 years (range 31–88). One hundred thirty-two patients were stabilized in 1 segment, 134 in 2 segments, 15 in 3 segments, and 2 patients in 4 segments. Reoperation rate for ASD and SL after 1 year was 7.4 %, after 2 years was 15.0%, and after a mean follow-up of 51.4±15 months was 22.6%. Reasons for revision were SL in 19 cases (6.6%), ASD in 39 cases (13.7%), SL and ASD in 6 cases, hematoma in 2 cases (0.7%), cerebrospinal fluid fistulae in 3 cases (1.1%), infection in 6 cases (2.1%), and implant failure in 1 case (0.4%). The patients' age, the number of stabilized segments, and the number of previous surgeries and postoperative LL had a significant influence on the probability for revision surgery.Conclusions
Reoperation rates after DS of the lumbar spine are comparable with rigid fixations. The younger the patient and the more segments are involved, the lower the LL and the more previous surgeries were found, the higher was the risk of revision. Risk of revision was almost twice as high in men compared with women. We therefore conclude that for clear clinical indication and careful evaluation of preoperative imaging data, DS using the Cosmic system seems to be a possible option. The presented data will help to further tailor indication and patient selection. 相似文献Background
Clear cell renal cell carcinoma (ccRCC) is known to occur across the adult lifetime traversing the spectrum of age-related organismal changes. Little is known as to how the aging process may affect the course of renal cell carcinoma (RCC) and the repertoire of genes involved.Methods
Using The Cancer Genome Atlas (n?=?436) and Cancer Genomics of the Kidney (n?=?89) datasets, we applied regression analysis to examine associations between patient age and gene expression profiles in ccRCC tumors and normal kidney tissues. Pathway enrichment analysis was performed to identify cellular process that is affected by aging in ccRCC. Moreover, connectivity mapping analysis was used to predict age-dependent response to drug treatments.Results
Our analysis revealed different age-dependent gene expression spectra in ccRCC and normal kidney tissues. These findings were significant and independently reproducible in both datasets examined. Age up-regulated genes, showing higher expression in older patients, were significantly enriched (false discovery rate <0.05) in normal tissues for pathways associated with immune response and extracellular matrix organization, whereas age up-regulated genes in tumors were enriched for metabolism and oxidation pathways. Strikingly, age down-regulated genes in normal cells were also enriched for metabolism and oxidation, while those in tumors were enriched for extracellular matrix organization. Further in silico analysis of potential drug targets predicted preferential efficacy of Phosphoinositide 3-kinase inhibitor or immunotherapy in association with age.Conclusion
We report on previously unrecognized associations between age and molecular underpinnings of RCC, including age-associated expression of genes implicated in RCC development or treatment. 相似文献Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献