Mycobacterium tuberculosis cords within lymphatic endothelial cells to evade host immunity.

The ability of Mycobacterium tuberculosis to form serpentine cords is intrinsically related to its virulence, but specifically how M. tuberculosis cording contributes to pathogenesis remains obscure. Here, we show that several M. tuberculosis clinical isolates form intracellular cords in primary human lymphatic endothelial cells (hLECs) in vitro and in the lymph nodes of patients with tuberculosis. We identified via RNA-Seq a transcriptional program that activated, in infected-hLECs, cell survival and cytosolic surveillance of pathogens pathways. Consistent with this, cytosolic access was required for intracellular M. tuberculosis cording. Mycobacteria lacking ESX-1 type VII secretion system or phthiocerol dimycocerosates expression, which failed to access the cytosol, were indeed unable to form cords within hLECs. Finally, we show that M. tuberculosis cording is a size-dependent mechanism used by the pathogen to avoid its recognition by cytosolic sensors and evade either resting or IFN-γ-induced hLEC immunity. These results explain the long-standing association between M. tuberculosis cording and virulence and how virulent mycobacteria use intracellular cording as strategy to successfully adapt and persist in the lymphatic tracts.

Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells.

BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans. Here, we examined the role of PDIM in Mtb translocation to the cytosol in hLECs. RESULTS: Analysis of a Mtb mutant unable to produce PDIM showed less co-localisation of bacteria with the membrane damage marker Galectin-8 (Gal8), indicating that PDIM strongly contribute to phagosomal membrane damage. Lack of this Mtb lipid also leads to a reduction in the proportion of Mtb co-localising with markers of macroautophagic removal of intracellular bacteria (xenophagy) such as ubiquitin, p62 and NDP52. hLEC imaging with transmission electron microscopy shows that Mtb mutants lacking PDIM are much less frequently localised in the cytosol, leading to a lower intracellular burden. CONCLUSIONS: PDIM is needed for the disruption of the phagosome membrane in hLEC, helping Mtb avoid the hydrolytic phagolysosomal milieu. It facilitates the translocation of Mtb into the cytosol, and the decreased intracellular burden of Mtb lacking PDIM indicates that the cytosol is the preferred replicative niche for Mtb in these cells. We hypothesise that pharmacological targeting of PDIM synthesis in Mtb would reduce the formation of a lymphatic reservoir of Mtb in humans.

Mycobacterium tuberculosis replicates within necrotic human macrophages.

Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage colony-stimulating factor-differentiated macrophages more than in granulocyte-macrophage colony-stimulating factor-differentiated macrophages. We show that permissiveness in the different populations of macrophages to bacterial growth is the result of a differential ability to preserve PM integrity. By combining live-cell imaging, correlative light electron microscopy, and single-cell analysis, we found that after infection, a population of macrophages became necrotic, providing a niche for M. tuberculosis replication before escaping into the extracellular milieu. Thus, in addition to bacterial dissemination, necrotic cells provide first a niche for bacterial replication. Our results are relevant to understanding the environment of M. tuberculosis replication in the host.

3D correlative light and electron microscopy of cultured cells using serial blockface scanning electron microscopy.

The processes of life take place in multiple dimensions, but imaging these processes in even three dimensions is challenging. Here, we describe a workflow for 3D correlative light and electron microscopy (CLEM) of cell monolayers using fluorescence microscopy to identify and follow biological events, combined with serial blockface scanning electron microscopy to analyse the underlying ultrastructure. The workflow encompasses all steps from cell culture to sample processing, imaging strategy, and 3D image processing and analysis. We demonstrate successful application of the workflow to three studies, each aiming to better understand complex and dynamic biological processes, including bacterial and viral infections of cultured cells and formation of entotic cell-in-cell structures commonly observed in tumours. Our workflow revealed new insight into the replicative niche of Mycobacterium tuberculosis in primary human lymphatic endothelial cells, HIV-1 in human monocyte-derived macrophages, and the composition of the entotic vacuole. The broad application of this 3D CLEM technique will make it a useful addition to the correlative imaging toolbox for biomedical research.

Interrupting peptidoglycan deacetylation during Bdellovibrio predator-prey interaction prevents ultimate destruction of prey wall, liberating bacterial-ghosts.

The peptidoglycan wall, located in the periplasm between the inner and outer membranes of the cell envelope in Gram-negative bacteria, maintains cell shape and endows osmotic robustness. Predatory Bdellovibrio bacteria invade the periplasm of other bacterial prey cells, usually crossing the peptidoglycan layer, forming transient structures called bdelloplasts within which the predators replicate. Prey peptidoglycan remains intact for several hours, but is modified and then degraded by escaping predators. Here we show predation is altered by deleting two Bdellovibrio N-acetylglucosamine (GlcNAc) deacetylases, one of which we show to have a unique two domain structure with a novel regulatory"plug". Deleting the deacetylases limits peptidoglycan degradation and rounded prey cell "ghosts" persist after mutant-predator exit. Mutant predators can replicate unusually in the periplasmic region between the peptidoglycan wall and the outer membrane rather than between wall and inner-membrane, yet still obtain nutrients from the prey cytoplasm. Deleting two further genes encoding DacB/PBP4 family proteins, known to decrosslink and round prey peptidoglycan, results in a quadruple mutant Bdellovibrio which leaves prey-shaped ghosts upon predation. The resultant bacterial ghosts contain cytoplasmic membrane within bacteria-shaped peptidoglycan surrounded by outer membrane material which could have promise as "bacterial skeletons" for housing artificial chromosomes.

Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis.

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.

Ankyrin-mediated self-protection during cell invasion by the bacterial predator Bdellovibrio bacteriovorus.

Predatory Bdellovibrio bacteriovorus are natural antimicrobial organisms, killing other bacteria by whole-cell invasion. Self-protection against prey-metabolizing enzymes is important for the evolution of predation. Initial prey entry involves the predator's peptidoglycan DD-endopeptidases, which decrosslink cell walls and prevent wasteful entry by a second predator. Here we identify and characterize a self-protection protein from B. bacteriovorus, Bd3460, which displays an ankyrin-based fold common to intracellular pathogens of eukaryotes. Co-crystal structures reveal Bd3460 complexation of dual targets, binding a conserved epitope of each of the Bd3459 and Bd0816 endopeptidases. Complexation inhibits endopeptidase activity and cell wall decrosslinking in vitro. Self-protection is vital - ΔBd3460 Bdellovibrio deleteriously decrosslink self-peptidoglycan upon invasion, adopt a round morphology, and lose predatory capacity and cellular integrity. Our analysis provides the first mechanistic examination of self-protection in Bdellovibrio, documents protection-multiplicity for products of two different genomic loci, and reveals an important evolutionary adaptation to an invasive predatory bacterial lifestyle.

The innate immune response in human tuberculosis.

Mycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini-review, we discuss these host-pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome-wide association studies).

Experimental selection of long-term intracellular mycobacteria.

Some intracellular bacteria are known to cause long-term infections that last decades without compromising the viability of the host. Although of critical importance, the adaptations that intracellular bacteria undergo during this long process of residence in a host cell environment remain obscure. Here, we report a novel experimental approach to study the adaptations of mycobacteria imposed by a long-term intracellular lifestyle. Selected Mycobacterium bovis BCG through continuous culture in macrophages underwent an adaptation process leading to impaired phenolic glycolipids (PGL) synthesis, improved usage of glucose as a carbon source and accumulation of neutral lipids. These changes correlated with increased survival of mycobacteria in macrophages and mice during re-infection and also with the specific expression of stress- and survival-related genes. Our findings identify bacterial traits implicated in the establishment of long-term cellular infections and represent a tool for understanding the physiological states and the environment that bacteria face living in fluctuating intracellular environments.

Silicate-substituted calcium phosphate as a bone graft substitute in surgery for adolescent idiopathic scoliosis.

STUDY DESIGN AND OBJECTIVE: The purpose of this prospective clinical study is to evaluate the clinical and radiographic outcomes using a silicate-substituted calcium phosphate (Si-CaP) as a bone graft substitute in surgery for adolescent idiopathic scoliosis (AIS). In posterior corrective surgery for AIS, harvesting autologous bone from the iliac crest still represents the gold standard to augment the local bone graft though it is comparatively invasive and associated with donor site morbidity. Si-CaP enriched with bone marrow aspirate (BMA) might be an appropriate bone graft extender to overcome these difficulties. METHODS: Eighteen female and three male patients with AIS who underwent corrective posterior instrumentation were observed clinically and radiographically for a minimum of 24 months. In all cases, 20-40 ml Si-CaP granules (ACTIFUSE) mixed with BMA from vertebral bodies was used to extend the local bone graft. Fusion was assessed by standardized conventional radiographs regarding loss of correction and implant failure. Clinical outcome was evaluated with use of the Scoliosis Research Society-22 patient Questionnaire (SRS-22) and a Visual Analog Scale (VAS) for back pain. RESULTS: Cobb angle of major curves averaged 63° preoperatively, 22° after surgery, and 24° at final follow-up, with a maximum loss of correction of 7° recorded after 4 months. No adverse effects related to the study material had been observed. In all patients, there was no evidence of implant failure, and formation of an increasingly densifying 'fusion mass' was visible, as assessed by conventional radiography. VAS score for back pain averaged 1.7 before surgery, 2.3 at discharge, and 1.5 at final follow-up. Outcome assessment using the SRS-22 revealed a significantly enhanced overall health-related quality of life (84 vs. 74 % before surgery; P = 0.0005) due to a significant improvement of the domains 'self image' (77 vs. 59 %; P = 0.0002) and 'pain' (88 vs. 80 %; P = 0.02). Patients' management satisfaction averaged 93 %. CONCLUSIONS: Si-CaP augmented with BMA from vertebral bodies seems to prove an effective, safe, and easy to handle bone graft extender in scoliosis surgery and thus a suitable alternative to bone harvesting procedures.

Genome analysis of a simultaneously predatory and prey-independent, novel Bdellovibrio bacteriovorus from the River Tiber, supports in silico predictions of both ancient and recent lateral gene transfer from diverse bacteria.

BACKGROUND: Evolution equipped Bdellovibrio bacteriovorus predatory bacteria to invade other bacteria, digesting and replicating, sealed within them thus preventing nutrient-sharing with organisms in the surrounding environment. Bdellovibrio were previously described as "obligate predators" because only by mutations, often in gene bd0108, are 1 in ~1x10(7) of predatory lab strains of Bdellovibrio converted to prey-independent growth. A previous genomic analysis of B. bacteriovorus strain HD100 suggested that predatory consumption of prey DNA by lytic enzymes made Bdellovibrio less likely than other bacteria to acquire DNA by lateral gene transfer (LGT). However the Doolittle and Pan groups predicted, in silico, both ancient and recent lateral gene transfer into the B. bacteriovorus HD100 genome. RESULTS: To test these predictions, we isolated a predatory bacterium from the River Tiber- a good potential source of LGT as it is rich in diverse bacteria and organic pollutants- by enrichment culturing with E. coli prey cells. The isolate was identified as B. bacteriovorus and named as strain Tiberius. Unusually, this Tiberius strain showed simultaneous prey-independent growth on organic nutrients and predatory growth on live prey. Despite the prey-independent growth, the homolog of bd0108 did not have typical prey-independent-type mutations. The dual growth mode may reflect the high carbon content of the river, and gives B. bacteriovorus Tiberius extended non-predatory contact with the other bacteria present. The HD100 and Tiberius genomes were extensively syntenic despite their different cultured-terrestrial/freshly-isolated aquatic histories; but there were significant differences in gene content indicative of genomic flux and LGT. Gene content comparisons support previously published in silico predictions for LGT in strain HD100 with substantial conservation of genes predicted to have ancient LGT origins but little conservation of AT-rich genes predicted to be recently acquired. CONCLUSIONS: The natural niche and dual predatory, and prey-independent growth of the B. bacteriovorus Tiberius strain afforded it extensive non-predatory contact with other marine and freshwater bacteria from which LGT is evident in its genome. Thus despite their arsenal of DNA-lytic enzymes; Bdellovibrio are not always predatory in natural niches and their genomes are shaped by acquiring whole genes from other bacteria.

Specialized peptidoglycan hydrolases sculpt the intra-bacterial niche of predatory Bdellovibrio and increase population fitness.

Bdellovibrio are predatory bacteria that have evolved to invade virtually all gram-negative bacteria, including many prominent pathogens. Upon invasion, prey bacteria become rounded up into an osmotically stable niche for the Bdellovibrio, preventing further superinfection and allowing Bdellovibrio to replicate inside without competition, killing the prey bacterium and degrading its contents. Historically, prey rounding was hypothesized to be associated with peptidoglycan (PG) metabolism; we found two Bdellovibrio genes, bd0816 and bd3459, expressed at prey entry and encoding proteins with limited homologies to conventional dacB/PBP4 DD-endo/carboxypeptidases (responsible for peptidoglycan maintenance during growth and division). We tested possible links between Bd0816/3459 activity and predation. Bd3459, but not an active site serine mutant protein, bound ß-lactam, exhibited DD-endo/carboxypeptidase activity against purified peptidoglycan and, importantly, rounded up E. coli cells upon periplasmic expression. A ΔBd0816 ΔBd3459 double mutant invaded prey more slowly than the wild type (with negligible prey cell rounding) and double invasions of single prey by more than one Bdellovibrio became more frequent. We solved the crystal structure of Bd3459 to 1.45 Å and this revealed predation-associated domain differences to conventional PBP4 housekeeping enzymes (loss of the regulatory domain III, alteration of domain II and a more exposed active site). The Bd3459 active site (and by similarity the Bd0816 active site) can thus accommodate and remodel the various bacterial PGs that Bdellovibrio may encounter across its diverse prey range, compared to the more closed active site that "regular" PBP4s have for self cell wall maintenance. Therefore, during evolution, Bdellovibrio peptidoglycan endopeptidases have adapted into secreted predation-specific proteins, preventing wasteful double invasion, and allowing activity upon the diverse prey peptidoglycan structures to sculpt the prey cell into a stable intracellular niche for replication.

Effects of orally administered Bdellovibrio bacteriovorus on the well-being and Salmonella colonization of young chicks.

Bdellovibrio bacteriovorus is a bacterium which preys upon and kills Gram-negative bacteria, including the zoonotic pathogens Escherichia coli and Salmonella. Bdellovibrio has potential as a biocontrol agent, but no reports of it being tested in living animals have been published, and no data on whether Bdellovibrio might spread between animals are available. In this study, we tried to fill this knowledge gap, using B. bacteriovorus HD100 doses in poultry with a normal gut microbiota or predosed with a colonizing Salmonella strain. In both cases, Bdellovibrio was dosed orally along with antacids. After dosing non-Salmonella-infected birds with Bdellovibrio, we measured the health and well-being of the birds and any changes in their gut pathology and culturable microbiota, finding that although a Bdellovibrio dose at 2 days of age altered the overall diversity of the natural gut microbiota in 28-day-old birds, there were no adverse effects on their growth and well-being. Drinking water and fecal matter from the pens in which the birds were housed as groups showed no contamination by Bdellovibrio after dosing. Predatory Bdellovibrio orally administered to birds that had been predosed with a gut-colonizing Salmonella enterica serovar Enteritidis phage type 4 strain (an important zoonotic pathogen) significantly reduced Salmonella numbers in bird gut cecal contents and reduced abnormal cecal morphology, indicating reduced cecal inflammation, compared to the ceca of the untreated controls or a nonpredatory ΔpilA strain, suggesting that these effects were due to predatory action. This work is a first step to applying Bdellovibrio therapeutically for other animal, and possibly human, infections.

Sagittal balance of thoracic lordoscoliosis: anterior dual rod instrumentation versus posterior pedicle screw fixation.

Posterior pedicle screw fixation is now the standard treatment for surgical correction of idiopathic scoliosis and has largely replaced anterior techniques, but there have been reports describing a lordogenic effect of segmental pedicle screw instrumentation in the thoracic spine. This clinical study compared anterior dual rod instrumentation with posterior pedicle screw fixation for idiopathic thoracic lordoscoliosis, including 42 patients (7 male, 35 female; average age 16 years, range 12-34) who underwent posterior pedicle screw fixation (n = 20) or anterior dual rod instrumentation (n = 22) at two centers. The average follow-up period was 33 months (24-108 months). Inclusion criteria were a diagnosis of adolescent idiopathic scoliosis with a structural thoracic curve (Lenke 1-3) and thoracic hypokyphosis (T4-T12 < 20°). The main thoracic curve magnitude and sagittal profile on standing radiographs were evaluated. Thoracic kyphosis was significantly restored from preoperatively 10.2° to 23.4° postoperatively in the anterior group and from 7.6° to 12.9° in the posterior group (P < 0.005). Kyphosis improved significantly better in the anterior group than in the posterior group (P < 0.005). The preoperative and postoperative main thoracic curve values were 63° (48-80°) and 25.2° in the anterior group and 60.6° (50-88°) and 23.6° in the posterior group, with no significant differences between the groups. No neurological or other severe complications were observed. Anterior dual rod instrumentation in patients with thoracic lordoscoliosis allows significantly better restoration of thoracic kyphosis than posterior pedicle screw instrumentation.

Long-term follow-up after en bloc resection and reconstruction of a solitary paraganglioma metastasis in the first lumbar vertebral body: a case report.

INTRODUCTION: Paragangliomas are rare tumors that originate from the autonomic nervous system-associated paraganglia. They metastasize infrequently. Malignancy can only be demonstrated by the presence of chromaffin tissue at sites where it usually is not present, such as bone, lung or liver, or local recurrence after total resection of a primary mass. Paragangliomas within the central nervous system are usually intradural near the conus medullaris. The metastatic spread of a retroperitoneal paraganglioma to a vertebral body is extremely rare, and there are only a few cases reported in the literature. CASE PRESENTATION: We report the case of a 16-year-old Caucasian girl who had undergone resection of a retroperitoneal paraganglioma that measured 15 × 11.5 × 9.5 cm. After further staging, a solitary metastatic paraganglioma was detected in the first lumbar vertebral body. After initial chemotherapy, marginal en bloc resection and reconstruction were performed followed by radiotherapy. Histologic examination of the specimen revealed that the tumor cells did not show any response to preoperative chemotherapy, which is in line with a few other reports in the literature. Ten years after operative treatment, the patient is free of complaints, very satisfied with the result and without signs of local recurrence or distant metastases. CONCLUSION: We recommend en bloc spondylectomy and local radiotherapy in the treatment of solitary spinal metastatic paragangliomas.

A level-1 pilot study to evaluate of ultraporous beta-tricalcium phosphate as a graft extender in the posterior correction of adolescent idiopathic scoliosis.

The objective of this study is to compare the clinical and radiographic results of ultraporous beta-tricalcium phosphate (beta-TCP) versus autogenous iliac crest bone graft (ICBG), through prospective randomized pilot study (EBM-Level 1), as graft extenders in scoliosis surgery. In the posterior correction of scoliosis, local bone resected as part of the procedure is used as the base bone graft material. Supplemental grafting from the iliac crest is considered the gold-standard in posterior spinal fusion. However, autograft is not available in unlimited quantities, and bone harvesting is a source of significant morbidity. Ultraporous beta-TCP might be a substitute for ICBG in these patients and thus eliminate donor site morbidity. A total of 40 patients with adolescent idiopathic scoliosis (AIS) were randomized into two treatment groups and underwent corrective posterior instrumentation. In 20 patients, ICBG harvesting was performed whereas the other half received beta-TCP (VITOSS) to augment the local bone graft. If thoracoplasty was performed, the resected rib bone was added in both groups. Patients were observed clinically and radiographically for a minimum of 20 months postoperatively, with a mean follow-up of 4 years. Overall pain and pain specific to the back and donor site were assessed using a visual analog scale (VAS). As a result, both groups were comparable with respect to the age at the time of surgery, gender ratio, preoperative deformity, and hence length of instrumentation. There was no significant difference in blood loss and operative time. In nine patients of the beta-TCP group and eight patients of the ICBG group, thoracoplasty was performed resulting in a rib graft of on average 7.9 g in both groups. Average curve correction was 61.7% in the beta-TCP group and 61.2% in the ICBG group at hospital discharge (P=0.313) and 57.2 and 54.3%, respectively, at follow-up (P=0.109). Loss of curve correction amounted on average 2.6 degrees in the beta-TCP group and 4.2 degrees in the comparison group (P=0.033). In the ICBG group, four patients still reported donor site pain of on average 2/10 on the VAS at last follow-up. One patient in the beta-TCP group was diagnosed with a pseudarthrosis at the caudal end of the instrumentation. Revision surgery demonstrated solid bone formation directly above the pseudarthrosis with no histological evidence of beta-TCP in the biopsy taken. In conclusion, the use of beta-TCP instead of ICBG as extenders of local bone graft yielded equivalent results in the posterior correction of AIS. The promising early results of this pilot study support that beta-TCP appears to be an effective bone substitute in scoliosis surgery avoiding harvesting of pelvic bone and the associated morbidity.

Raster stereography versus radiography in the long-term follow-up of idiopathic scoliosis.

STUDY DESIGN: Raster-stereographic and radiographic evaluation of idiopathic scoliosis without braces in a retrospective longitudinal long-term follow-up study. OBJECTIVE: To investigate the reliability and accuracy of raster stereography in comparison with radiography as the gold standard, using a longitudinal long-term study design in idiopathic scoliosis, to reduce the number of radiographs required during follow-up in scoliosis patients. SUMMARY OF BACKGROUND DATA: It has been confirmed that raster stereography produces reliable data in patients with conservatively and surgically treated idiopathic scoliosis, up to a Cobb angle of 80 degrees. This means that the method can be used to replace radiography during the follow-up in these patients. However, no data have yet been published on the use of raster stereography in a longitudinal setting during a long-term follow-up period in comparison with radiography as the gold standard. METHODS: Raster stereographs and digitized anterior-posterior radiographs of 16 patients with idiopathic scoliosis were studied retrospectively in a longitudinal study design, with a mean follow-up period of 8 years (range 3 to 10 y). Lateral vertebral deviation and vertebral rotation were measured between C7 and L4 using raster stereography and radiography, compared with Cobb angles, and correlated. RESULTS: During the follow-up period, the Cobb angle increased on average by 13 degrees. The progression of lateral vertebral deviation measured using both techniques, and that of vertebral rotation measured with radiography, was greater than that of the Cobb angle, whereas that of raster-stereographic vertebral rotation was lower. However, there was an excellent correlation between the raster-stereographic and radiographic progression of these parameters (R2 >or=0.5). The mean difference between raster stereographs and radiographs was 3.21 mm for lateral vertebral deviation and 2.45 degrees for vertebral rotation. CONCLUSIONS: Using the parameters of lateral vertebral deviation and vertebral rotation, raster stereography accurately reflects the radiographically measured progression of idiopathic scoliosis during the long-term follow-up, but these parameters are not directly comparable with the Cobb angle. In the follow-up of scoliosis patients, the authors would recommend a raster-stereographic examination every 3 to 6 months and a radiographic examination every 12 to 18 months only, provided that raster stereography does not show rapid deterioration of the scoliosis. The patient's radiation exposure can be reduced using this approach.

En bloc spondylectomy in malignant tumors of the spine.

En bloc spondylectomy is a technique that enables wide or marginal resection of malignant lesions of the spine. Both all posterior techniques as well as combined approaches are reported. Aim of the present study was to analyse the results of 21 patients with malignant lesions of the spine, all treated with en bloc excision in a combined posteroanterior (n = 19) or all posterior approach (n = 2). Twenty-one consecutive patients, operated between 1997 and 2005, were included into this retrospective study. Thirteen patients had primary malignant lesions, eight patients had solitary metastases, all located in the thoracolumbar spine. There were 16 single level, three two-level, one three-level and one four-level spondylectomy. The patients were followed clinically and radiographically (including CT studies) with an average follow-up of 4 years. Out of 11 patients with primary Ewing or osteosarcoma seven patients are alive without any evidence of disease. One patient died after 5 years from other causes and three are alive with evidence of disease. Latter had either a poor histologic response to the preoperative chemotherapy (n = 2) or an intralesional resection (n = 1). All three patients with solitary spinal metastases of Ewing or osteosarcoma died of the disease. Five patients with solitary metastases of mainly hypernephroma are alive. In total, six resections were intralesional, mainly due to large intraspinal tumor masses, with two patients having had previous surgery. In the remaining cases, wide (n = 10) or marginal (n = 5) resection was accomplished. There were one pseudarthrosis requiring extension of the fusion and two cases with local recurrences and repeated excisional surgery. At follow-up CT studies, all cages were fused. Health related quality of life analysis (SF-36) revealed only slightly decreased physical component and normal mental component scores compared to normals in those patients with no evidence of disease. En bloc spondylectomy enables wide or marginal resection of malignant lesions of the spine in most cases with acceptable morbidity. Intralesional resection, poor histologic response, and solitary spinal metastases of Ewing and osteosarcoma are associated with a poor prognosis.

Acquired spondylolysis after implantation of a lumbar ProDisc II prosthesis: case report and review of the literature.

STUDY DESIGN: A case of acquired lumbar spondylolysis following lumbar disc arthroplasty L5-S1 in an 40-year-old woman and review of the literature. OBJECTIVES: To present and discuss a case of acquired lumbar spondylolysis after implantation of an artificial disc L5-S1 that may have impaired a good clinical result requiring additional posterior lumbar instrumentation and fusion in order to improve understanding of this condition and to propose an effective method of surgical management. SUMMARY OF BACKGROUND DATA: Lumbar disc arthroplasty is a possible surgical option for patients with degenerative disc disease. Acquired spondylolysis is a rare but known complication of spinal fusion but has never been described as a consequence of mobile disc arthroplasty. The authors present the first case in the literature who developed this complication. METHODS: A 40-year-old woman with severe osteochondrosis L5-S1 and discogenic lumbar back pain underwent implantation of an artificial disc. Surgery and postoperative course were uneventful and the patient improved significantly as for back pain and mobility. Eighteen months after surgery, the patient was again admitted to our outpatient clinic for back pain that had slowly increased over time. RESULTS: The radiologic workup showed a new spondylolysis L5 without a spondylolisthesis. Because of unsuccessful conservative treatment, the patient underwent posterior lumbar instrumentation and fusion L5-S1, leading to a significant pain reduction and a good clinical outcome. CONCLUSION: Spine surgeons should be aware of the possibility of lumbar disc arthroplasty to induce acquired spondylolysis impairing good clinical results.