Expression of serglycin in human disc is increased in degenerated discs and up-regulated in vitro by exposure to IL-1ß or TNF-α.

We investigated whether the multifunctional intercellular proteoglycan, serglycin, is expressed in human intervertebral disc cells and assessed its localization. We also investigated expression levels of serglycin in human annulus fibrosus (annulus) cells exposed to IL-1ß and TNF-α, which are two proinflammatory cytokines that are expressed during disc degeneration. Immunolocalization of serglycin was common in many cells of the human annulus, but less common in the nucleus pulposus (nucleus). Both intracellular and cell membrane localization were observed. Annulus cells from Thompson grades III, IV and V degenerated discs exhibited a 4.69 fold up-regulation in serglycin expression vs. cells from healthier grades I and II discs. In monolayer annulus cell culture, cells from more degenerated discs exhibited a 9.4 fold up-regulation of serglycin expression compared to cells from healthier discs. Exposure of cultured cells to IL-1ß or TNF-α caused significant up-regulation of serglycin expression. We found that serglycin expression increased with increasing disc degeneration both in vivo and in vitro, and also increased with exposure in vitro to IL-1ß and TNF-α.

The chemokine, CXCL16, and its receptor, CXCR6, are constitutively expressed in human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL-1ß in vitro.

Chemokines are an important group of soluble molecules with specialized functions in inflammation. The roles of many specialized chemokines and their receptors remain poorly understood in the human intervertebral disc. We investigated CXCL16 and its receptor, CXCR6, to determine their immunolocalization in disc tissue and their presence following exposure of cultured human annulus fibrosus cells to proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can induce hypoxia-inducible factor 1α (HIF-1α), which is a phenotypic marker of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in many cells of the annulus portion of the disc. Molecular studies showed that annulus fibrosus cells exposed to IL-1ß, but not TNF-α, exhibited significant up-regulation of CXCL16 expression vs. control cells. There was no significant difference in the percentage of annulus cells that exhibited immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens. The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests the need for future research concerning the role of this chemokine in proinflammatory functions, HIF-1α expression and disc vascularization.

Coccygectomy for patients with chronic coccydynia: a prospective, observational study of 98 patients.

AIMS: The purpose of this prospective study was to evaluate the outcomes of coccygectomy for patients with chronic coccydynia. PATIENTS AND METHODS: Between 2007 and 2011, 98 patients underwent coccygectomy for chronic coccydynia. The patients were aged > 18 years, had coccygeal pain, local tenderness and a radiological abnormality, and had failed conservative management. Outcome measures were the Short Form 36 (SF-36), the Oswestry Disability Index (ODI) and a visual analogue scale (VAS) for pain. Secondary analysis compared the pre-operative features and the outcomes of patients with successful and failed treatment, two years post-operatively. The threshold for success was based on a minimum clinically important difference (MCID) on the ODI of 20 points. All other patients, including those lost to follow-up, were classified as failures. RESULTS: There was significant improvement in all ten components of the SF-36 (p < 0.05), the ODI (23 points) and VAS (39 points) (p < 0.0001). A total of 69 patients (70.4%) met the designated MCID threshold for a successful outcome. The failure group consisted of 25 patients (25.5%) who did not reach the MCID and four (4.1%) who were lost to follow-up. Six patients (6.1%) in the failure group had ODI scores that were no better or worse than that pre-operatively. The patients in whom treatment failed had significantly worse pre-operative scores for the ODI (p = 0.04), VAS (p = 0.02) and on five of ten SF-36 components (p < 0.04). They also had a higher incidence of psychiatric disorders, pre-operative opiate use and more than three comorbidities. TAKE HOME MESSAGE: Coccygectomy for chronic coccydynia results in significant improvement in patient-reported outcomes at two years. Failure is associated with certain pre-operative characteristics such as psychiatric illness, poor quality of life features, higher levels of pain, and use of opiates.

Increased IL-17 expression in degenerated human discs and increased production in cultured annulus cells exposed to IL-1ß and TNF-α.

IL-17 is expressed in a number of tissues including the intervertebral disc, where it exerts strong inflammatory properties. We evaluated IL-17 using immunolocalization in herniated and non-herniated human discs, IL-17 gene expression, and the production of IL-17 by annulus cells cultured in three dimensions in the presence of IL-1ß or TNF-α. There was no difference in the percentage of IL-17 positive cells in annulus or nucleus in herniated vs. non-herniated disc specimens. Molecular studies confirmed expression of IL-17 in disc tissue, with significantly increased expression in more degenerated discs; there was no difference in expression between herniated vs. non-herniated discs. Exposure to IL-1ß or TNF-α resulted in significantly greater production of IL-17. Our findings expand understanding of IL-17 production by disc cells and reveal the importance of non-canonical IL-17 production in the disc. Significantly greater expression of IL-17 in more degenerated discs adds to our understanding of the changes in disc cell function with advancing stages of disc degeneration.

Human adipose-derived mesenchymal stem cells: serial passaging, doubling time and cell senescence.

Adult adipose-derived mesenchymal stem cells (AD-MSC) are very interesting to our research group because they are easy to harvest, they are abundant in humans, and they have potential clinical applications in autologous cell therapy for disc degeneration. We examined these cells through sequential serial passages to assess osteogenic and chondrogenic capabilities, mean doubling time and cell senescence. Osteogenic and chondrogenic potencies were maintained through 13 passages. Mean passage doubling time increased significantly with increasing passage number. When donor age was evaluated, passages 1-4 from older donors had significantly longer doubling times compared to cells from younger donors. Passages 5-11 showed similar findings when analyzed by donor age. The mean percent senescence increased significantly with cell passaging, rising from 0% at passage 1 to 3.4% at passage 13. These novel data suggest that caution should be exercised when using AD-MSC with long passage times.

The musculoskeletal effects of smoking.

Currently, there are more than 50 million smokers in this country, and approximately 800 billion cigarettes are smoked each year. Smoking is now the leading avoidable cause of morbidity and mortality in the United States. According to one report, over 500,000 deaths per year in the United States alone can be attributed to smoking. For years, orthopaedic surgeons have known about the relationships that putatively exist between smoking and an array of orthopaedic conditions and complications. It has been shown to adversely affect bone mineral density, lumbar disk disease, the rate of hip fractures, and the dynamics of bone and wound healing. Although scientific and clinical information on smoking and its consequences suggests differing degrees of correlation between smoking and orthopaedic conditions, most available data do suggest a real and reproducible relationship. In the past, there have been many individual reports that deal with these relationships separately but very few published comprehensive reviews. This summary of the current literature regarding the relationship between smoking and musculoskeletal diseases and their treatment provides information that can be used clinically by both the practitioner and the patient.

Effects of very high antibiotic concentrations on human intervertebral disc cell proliferation, viability, and metabolism in vitro.

STUDY DESIGN: Four antibiotics commonly used during spinal surgery (cefazolin, gentamycin, cefamandole, and vancomycin) were tested for their effects on cultured human disc cells from the anulus. OBJECTIVE: To determine the viability, proliferation, and metabolism of cells cultured from the human anulus after they were exposed to four antibiotics. SUMMARY OF BACKGROUND DATA: Previous studies concerning the effect of antibiotics on the disc have used animal models or explanted discs, but little is understood about the effect of antibiotics on the proliferation, viability, and metabolism of cells from the anulus. METHODS: In this study, 3H-thymidine incorporation, trypan blue exclusion, and cell metabolism were determined using cells from the human anulus grown in monolayer culture. The latter measurement used a cytosensor microphysiometer to monitor the rate at which cells acidified their microenvironment, an event that is proportional to cellular metabolism because it reflects the excretion over time of acidic products such as lactic acid from glycolysis and CO2 from cellular respiration. RESULTS: After 48 hours of antibiotic exposure, cell viability was significantly lower as a result of all four antibiotics at the highest concentration tested. Cell proliferation was lower after exposure to cefazolin and cefamandole. During a 6-hour antibiotic exposure, anulus cells in the highest concentration of cefamandole or vancomycin displayed a significantly decreased rate of cell metabolism. CONCLUSIONS: These findings show that high doses of antibiotics can have direct, deleterious effects on cultured disc cell survival, cell proliferation, and metabolic rates. Discitis is a serious primary or postoperative complication that often requires prolonged antibiotic treatment. Studies such as the current investigation with cultured cells from the anulus show the importance of a greater understanding concerning antibiotic effects on disc cell proliferation and metabolism.

Interobserver reliability and intraobserver reproducibility of the modified Ficat classification system of osteonecrosis of the femoral head.

Anteroposterior and lateral plain radiographs of 116 osteonecrotic femoral heads were reviewed to assess the interobserver reliability and intraobserver reproducibility of the modified Ficat classification system. The radiographs were reviewed initially and then again six months later by three adult reconstructive surgeons, two general orthopaedic surgeons, two orthopaedic residents, and one musculoskeletal radiologist. All eight observers agreed on the classification of twenty hips (17 per cent) at both the first and the second review of the radiographs. Paired comparisons revealed a mean interobserver kappa reliability coefficient of 0.46 (range, 0.30 to 0.67) for the first review and 0.45 (range, 0.30 to 0.66) for the second. For all observers, the mean rate of perfect agreement between the first and the second review was 68 per cent (range, 56 to 80 per cent). The mean kappa value for intraobserver reproducibility was 0.59 (range, 0.44 [one of the residents] to 0.73 [one of the general orthopaedic surgeons]). No observer or pair of observers had excellent reproducibility or reliability (kappa > 0.75). The poor interobserver reliability and fair intraobserver reproducibility diminishes any meaningful comparison of studies in which the modified Ficat classification system has been used and illuminates the need for a more reliable and reproducible classification system.

Cigarette smoking and its orthopedic consequences.

Cigarette smoking and its ramifications are coming under increasing scrutiny in the field of orthopedic surgery. Smoking has been implicated in impeding bone metabolism and fracture repair, and increasing the rate of postoperative infection and the incidence of nonunion. This article reviews the current body of knowledge on these topics, as well as the potential adverse effects of smoking on wound healing and microsurgical procedures. An in-depth discussion on the pathophysiologic mechanisms of nicotine is also included.

Indications for fusion in the lumbar spine.

A wide variety of lumbar spinal conditions have been managed by spinal fusion. Results appear better when the diagnosis is specific and related to definable instability or deformity in patients with a stable psychologic state. Success rates are higher in isthmic spondylolisthesis, unstable spinal stenosis syndromes (degenerative spondylolisthesis, degenerative scoliosis), and in patients with objective segmental instability. Variable success rates are reported for disk-related low back pain conditions and in patients with failed previous surgery. Instrumentation appears to be beneficial in situations in which complex deformities or obvious instability are present.

The indications for lumbar spinal fusion with and without instrumentation.

STUDY DESIGN: Literature review. OBJECTIVES: A review, analysis, and discussion of the extensive literature on lumbar spinal fusion were done to attempt to place in perspective the indications and success rate for lumbar spinal fusion with and without instrumentation. SUMMARY OF BACKGROUND DATA: A wide variety of lumbar spinal conditions have been managed by spinal fusion. Results appear better when the diagnosis is very specific and related to definable instability or deformity in patients with a stable psychologic state. METHODS: Search of literature. RESULTS: Success rates are higher in isthmic spondylolisthesis, unstable spinal stenosis syndromes (degenerative spondylolisthesis, degenerative scoliosis), and in patients with objective segmental instability. Variable success rates are reported for disc-related low back pain conditions and in patients with failed previous surgery. Instrumentation appears to be beneficial in situations where complex deformities or obvious instability is present. When applied for other diagnoses (e.g., internal disc disruption), results appear no better than with traditional surgical techniques. CONCLUSIONS: The outcome of lumbar spinal fusion depends on careful assessment of the anatomic cause of pain and of the patient's functional state and expectations.

Extracting knowledge from large medical databases: an automated approach.

Tools which can uncover patterns in patients' records and then make predictions based on that knowledge are and will continue to be high priority in many medical informatics groups. These tools are impacting the performance of outcome studies by discovering patterns which can then be verified with standard statistical tools. This paper demonstrates INC2.5, a general classification system, as a tool for assisting physicians in the decision making process. INC2.5 gathers information from patient records and builds a decision tree which is used to assist physicians in predicting the outcome of new patients. The decision tree will also reveal any patterns which the system found in the data. Successful results of such a system can be used to enhance outcome studies as well as to spread clinical information to areas with fewer resources.

Lumbar intervertebral disc transfer. A canine study.

STUDY DESIGN: Degenerative lumbar disc disease has been implicated as a cause of low back pain. Current treatment options for low back pain involve nonphysiologic fusion of the involved segments and have variable success rates. This is an experimental study of lumbar intervertebral disc transplantation using a canine surgical model. OBJECTIVES: This study evaluated the feasibility of lumbar disc transplantation and its effects on disc metabolism and morphology. METHOD: Eight mature mongrel dogs underwent disc transfer surgeries, in which the L2-L3 and L4-L5 intervertebral discs, with a small segment of adjacent superior and inferior vertebral body, were removed and transposed. The transplanted disc were stabilized by plates or by a flexible cable wire construct using Songer cables (DANEK, Inc., Memphis, TN). Unrestricted activity was allowed postoperatively. At 4 months, the spines were harvested, and the transplanted discs were evaluated biochemically and histologically. Intervening nontransplanted discs served as viable controls and thrice-frozen discs served as nonviable controls. Cell viability was assessed by measuring proteoglycan synthesis and DNA content. RESULTS: Proteoglycan synthesis (35S uptake normalized to DNA content) was maintained in transplanted anulus fibrosus tissue, but was decreased in nucleus pulposus samples (P < 0.05). DNA content was not altered significantly in the transplanted discs. Histologic analysis of the transplanted discs showed revascularization and remodeling of the bone adjacent to the disc and preservation of the lamellar architecture of the anulus fibrosus. The transplanted nucleus pulposus samples had chondrocyte-like cells present, but the staining characteristics of the nucleus material was variable. The contour of the transplanted disc endplates was irregular in all specimens. CONCLUSIONS: The structure and function of autograft intervertebral discs were maintained after disc transfer surgery; the transplant discs, however, were not completely normal in either their morphology or their metabolic functioning.

Vascular surgery: possible adverse effect on extent of subsequent lower limb amputation.

The influence of previous vascular surgery on the level of amputation was examined retrospectively in 345 amputations (66 bilateral) in 279 patients with peripheral vascular disease. Seventy-two patients (38% diabetic) had previous vascular surgery on 74 limbs and 207 (65% diabetic) had no history of vascular surgery on 271 limbs. In patients with previous vascular surgery, above-knee amputation was done on 55% of limbs versus 71% of limbs in patients with no previous vascular surgery (P < .05), despite a lower incidence of diabetes in the former group. We conclude that although reconstructive vascular surgery is an effective treatment for vascular insufficiency, occasionally it not only fails, but is associated with an increased incidence of above-knee amputation.

Junctional burst fractures.

Twenty-two patients with burst fractures in this mechanically and neurologically distinct region (T11-L2) were studied at injury and after acute surgical reduction and stabilization (antikyphosis and ligamentotaxis concept). Canal compromise averaged 42% (10-82%) before surgery, and at follow-up 14% (0-46%), segmental kyphosis 15 degrees (4 degrees-27 degrees) and 3 degrees (0 degree-15 degrees), and vertebral segment height 62% (41-85%) and 86% (60-100%), respectively. Incomplete patients gained an average of 1.8 Frankel subgrades. The described treatment can predictably recanalize the spine, correct deformity, and stabilize neurologic compromise. A significant correlation between postoperative neurologic status and the radiographic criteria under study could not be established.

Decompression and luque rectangle fusion for degenerative spondylolisthesis.

Detailed follow-up at an average of 21.3 months is reported for 24 patients undergoing decompression and fusion with the Luque rectangle as a tension band device for spinal stenosis secondary to degenerative spondylolisthesis. Leg pain and back pain were improved at rates of 91% and 90%, respectively. The average distance walked increased from 1.1 blocks preoperatively to 6.8 blocks postoperatively. The fusion rate was 96%, and minimal slip progression was observed. The instrumentation is simple to perform and appears to have few complications.

The development of low-back pain after excision of a lumbar disc.

One hundred and twenty consecutive patients who had primary excision of a lumbar disc at a single level for predominantly radicular symptoms were studied. Of these patients, eighty-seven (72 per cent) were available for comprehensive review. The duration of follow-up ranged from twenty-four to eighty-seven months (average, thirty-eight months). Radiculopathy was initially relieved in eighty-six (99 per cent) of the patients, although six patients (7 per cent) had recurrent herniation, which was successfully treated by reoperation. In an additional twelve patients (14 per cent), the operation was deemed a failure due to subsequent disabling low-back pain. Narrowing of the disc space was present radiographically in 98 per cent of the patients, but the amount of narrowing did not correlate with the degree of low-back pain, the age of the patient, or the length of time after operation. Factors predisposing to failure of the operation due to disabling low-back pain included coverage under Workmen's Compensation (p less than 0.00001), a history of more than fifteen pack-years of cigarette-smoking (average, one pack a day for fifteen years) (p less than 0.01), and an age of more than forty years (p less than 0.05).