Abstract
Odontoid fractures are the most common fracture of the axis and the most common cervical spine fracture in patients over 65. Despite their frequency, there is considerable ambiguity ...regarding optimal management strategies for these fractures in the elderly. Poor bone health and medical comorbidities contribute to increased surgical risk in this population; however, nonoperative management is associated with a risk of nonunion or fibrous union. We provide a review of the existing literature and discuss the classification and evaluation of odontoid fractures. The merits of operative vs nonoperative management, fibrous union, and the choice of operative approach in elderly patients are discussed. A treatment algorithm is presented based on the available literature. We believe that type I and type III odontoid fractures can be managed in a collar in most cases. Type II fractures with any additonal risk factors for nonunion (displacement, comminution, etc) should be considered for surgical management. However, the risks of surgery in an elderly population must be carefully considered on a case-by-case basis. In a frail elderly patient, a fibrous nonunion with close follow-up is an acceptable outcome. If operative management is chosen, a posterior approach is should be chosen when fracture- or patient-related factors make an anterior approach challenging. The high levels of morbidity and mortality associated with odontoid fractures should encourage all providers to pursue medical co-management and optimization of bone health following diagnosis.
Aging is a major risk factor of intervertebral disc degeneration and a leading cause of back pain. Pathological changes associated with disc degeneration include the absence of large, vacuolated and ...reticular‐shaped nucleus pulposus cells, and appearance of smaller cells nested in lacunae. These small nested cells are conventionally described as chondrocyte‐like cells; however, their origin in the intervertebral disc is unknown. Here, using a genetic mouse model and a fate mapping strategy, we have found that the chondrocyte‐like cells in degenerating intervertebral discs are, in fact, nucleus pulposus cells. With aging, the nucleus pulposus cells fuse their cell membranes to form the nested lacunae. Next, we characterized the expression of sonic hedgehog (SHH), crucial for the maintenance of nucleus pulposus cells, and found that as intervertebral discs age and degenerate, expression of SHH and its target Brachyury is gradually lost. The results indicate that the chondrocyte‐like phenotype represents a terminal stage of differentiation preceding loss of nucleus pulposus cells and disc collapse.
Lineage tracing of neonatal mouse nucleus pulposus (NP) cells of the intervertebral disc using Krt19CreERT; R26mT/mG line shows that reticular‐shaped NP cells differentiate into the chondrocyte‐like cell (CLCs) with aging. The study also shows that the nested CLCs are formed by the fusion of several NP cells. And differentiation of NP into CLC was associated with a decline in the expression of SHH and Brachyury.
Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC ...remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with
loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.
Abstract Background context Adjacent segment disease (ASD) is symptomatic deterioration of spinal levels adjacent to the site of a previous fusion. A critical issue related to ASD is whether ...deterioration of spinal segments adjacent to a fusion is due to the spinal intervention or due to the natural history of spinal degenerative disease. Purpose The purpose of this review is to summarize the recent clinical literature on adjacent segment disease in light of the natural history, patient-modifiable risk factors, surgical risk factors, sagittal balance, and new technology. Study design This review will evaluate the recent literature on genetic and hereditary components of spinal degenerative disease and potential links to the development of ASD. Methods After a meticulous search of Medline for relevant articles pertaining to our review, we summarized the recent literature on the rate of ASD and the effect of various interventions, including motion preservation, sagittal imbalance, arthroplasty, and minimally invasive surgery. Results The reported rate of ASD after decompression and stabilization procedures is approximately 2% to 3% per year. The factors that are consistently associated with adjacent segment disease include laminectomy adjacent to a fusion and a sagittal imbalance. Conclusions Spinal surgical interventions have been associated with ASD. However, whether such interventions may lead to an acceleration of the natural history of the disease remains questionable.
The reaction dynamics of excited electronic states in nucleic acid bases is a key process in DNA photodamage. Recent ultrafast spectroscopy experiments have shown multicomponent decays of excited ...uracil and thymine, tentatively assigned to nonadiabatic transitions involving multiple electronic states. Using both quantum chemistry and first principles quantum molecular dynamics methods we show that a true minimum on the bright S2 electronic state is responsible for the first step that occurs on a femtosecond time scale. Thus the observed femtosecond decay does not correspond to surface crossing as previously thought. We suggest that subsequent barrier crossing to the minimal energy S2/S1 conical intersection is responsible for the picosecond decay.
Retrospective review.
(1) To describe change in treatment patterns for degenerative spondylolisthesis (DS). (2) To report regional variation in treatment of DS. (3) To describe variation in ...surgeon-reported outcomes for DS based on treatment.
Spinal stenosis associated with DS is commonly treated with decompression and fusion but little is known about the optimal fusion technique. During a 6-month period, American Board of Orthopaedic Surgery step II candidates submit procedure lists; these lists have been stored in an electronic database since 1999.
The American Board of Orthopaedic Surgery database was retrospectively queried to identify patients who underwent surgery for DS from 1999 to 2011. Included patients underwent uninstrumented fusion, fusion with posterior instrumentation, fusion using interbody device, or decompression without fusion. Utilization of these procedures was analyzed by year and geographic region.
The study period included 5639 cases; the annual number of cases doubled during the study period. The percentage of cases treated with interbody fusion (IF) increased significantly throughout the study period, from 13.6% (1999-2001) to 32% (2009-2011) (P<0.001). The percentage of DS cases treated with posterolateral fusion peaked in 2003 then decreased as the rate of IF increased. In 2011, the rates of posterolateral fusion (40%) and posterolateral fusion with IF (37%) were nearly identical. The Northwest had the highest rate of IF (41%), >10% higher than any other region (P<0.001) and more than 23% higher than the Southeast (P<0.001).
Despite little evidence guiding treatment strategy for DS, national treatment patterns have changed dramatically during the past 13 years. The rapid adoption of IF and substantial regional variation in treatment utilization patterns raises questions about drivers of change including perceptions about associated fusion rates, the importance of sagittal balance and differential reimbursement.
4.
Retrospective subgroup analysis of prospectively collected data according to treatment received.
The purpose of this study was to determine whether obesity affects treatment outcomes for lumbar ...stenosis (SpS) and degenerative spondylolisthesis (DS).
Obesity is thought to be associated with increased complications and potentially less favorable outcomes after the treatment of degenerative conditions of the lumbar spine. This, however, remains a matter of debate in the existing literature.
An as-treated analysis was performed on patients enrolled in the Spine Patient Outcomes Research Trial for the treatment of SpS or DS. A comparison was made between patients with a body mass index (BMI) of less than 30 ("nonobese," n = 373 SpS and 376 DS) and those with a BMI of 30 or more ("obese," n = 261 SpS and 225 DS). Baseline patient characteristics, intraoperative data, and complications were documented. Primary and secondary outcomes were measured at baseline and regular follow-up time intervals up to 4 years. The difference in improvement over baseline between surgical and nonsurgical treatment (i.e., treatment effect) was determined at each follow-up interval for the obese and nonobese groups.
At 4-year follow-up, operative and nonoperative treatment provided improvement in all primary outcome measures over baseline in patients with BMI of less than 30 and 30 or more. For patients with SpS, there were no differences in the surgical complication or reoperation rates between groups. Patients with DS with BMI of 30 or more had a higher postoperative infection rate (5% vs. 1%, P = 0.05) and twice the reoperation rate at 4-year follow-up (20% vs. 11%, P = 0.01) than those with BMI of less than 30. At 4 years, surgical treatment of SpS and DS was equally effective in both BMI groups in terms of the primary outcome measures, with the exception that obese patients with DS had less improvement from baseline in the 36-Item Short Form Health Survey (SF-36) physical function score than nonobese patients (22.6 vs. 27.9, P = 0.022). With nonoperative treatment, patients with SpS with BMI of 30 or more did worse in regard to all 3 primary outcome measures, and patients with DS with BMI of 30 or more had similar SF-36 bodily pain scores but less improvement over baseline in the SF-36 physical function and Oswestry Disability Index scores. Treatment effects for SpS and DS were significant within each BMI group for all primary outcome measures in favor of surgery. Obese patients had a significantly greater treatment effect than nonobese patients with SpS (Oswestry Disability Index, P = 0.037) and DS (SF-36 PF, P = 0.004) largely due to the relatively poor outcome of nonoperative treatment in obese patients.
Obesity does not affect the clinical outcome of operative treatment of SpS. There are higher rates of infection and reoperation and less improvement from baseline in the SF-36 physical function score in obese patients after surgery for DS. Nonoperative treatment may not be as effective in obese patients with SpS or DS.
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