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Medical treatment with antibiotic therapy remains the mainstay of treatment for pyogenic spondylodiscitis (PS). Nevertheless, orthopaedic treatment is also very important in relieving pain, preventing neurological damage, and avoiding development of spinal deformities (e.g., scoliosis, kyphosis) due to spinal instability. Rigid thoracolumbosacral orthosis (TLSO) bracing is often needed in patients with PS, and average duration of treatment of 3 to 4 months. However, TLSO bracing can be poorly tolerated and limit ability of the patient to go back to a normal life. In 2004 our group developed an alternative surgical treatment to TLSO bracing by percutaneous posterior screw-rod bridge instrumentation of the infected level. This treatment allows early and free mobilization of the patients and is associated with faster recovery, lower pain scores and improved quality of life as previously reported. Herein, we report the clinical outcome of the first 3 patients who have completed the 10 years follow-up mark after the procedure. A case report is also described and details of the procedure are provided.

Background: Treatment of complex foot deformities in growing children and young adult patients is challenging. The traditional approach consists of extensive soft tissues releases, osteotomies and/or arthrodesis. More recently, distraction osteogenesis has been proposed as an alternative strategy. The aim of this study was to describe our treatment strategy and report clinical outcomes of the patients affected from complex foot deformities treated by distraction osteogenesis and hexapod external fixator.Materials and methods: We retrospectively reviewed 10 consecutive patients with complex foot and ankle deformities treated from 2014 to 2016 at our unit. A TrueLok external fixator system was used in all patients. Final outcome was classified as good, fair and poor according to the criteria indicated by Paley and Ferreira. The results were also evaluated by the pre-operative and post operative American Orthopedic Foot and Ankle Score (AOFAS) and The Manchester-Oxford Foot Questionnaire (MOXFQ).Results: A plantigrade foot was obtained in eight patients at the end of treatment, while in two patients a recurrence of the deformity was noted. Result was classified as good in 6 patients, fair in 2 patients, and poor in 2 patients. The AOFAS score improved from 33.9 +/- 21.2 pre-operatively to 67.25 +/- 15.1 post-operatively (p = 0.005). A statistically significant improvement was observed for the MOXFQ score as well (from 60.6 +/- 23.3 to 33.0 +/- 25.2, p = 0.020).Conclusions: Our study shows that the TrueLok hexapod external fixator is a safe and effective tool in treatment of complex rigid foot deformities. Nevertheless, deformity recurrence can be observed in some cases and treatment remains challenging. Distraction osteogenesis should be reserved as a salvage solution for particularly complex cases and should be performed at dedicated specialized centers. (C) 2018 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Knee osteoarthritis (KOA) is a very common condition with multifactorial etiology leading to severe pain and disability in the adult population. Although KOA is considered a non-inflammatory arthritis, upregulation of inflammatory and catabolic pathways with increased production of pro-inflammatory cytokines leading to cartilage degradation and extracellular matrix degeneration has been reported. Intra-articular injection of fresh fat derived stromal vascular fraction (SVF) fraction has been proposed as a valid and alternative treatment for symptomatic KOA that guarantees mechanical support through viscosupplementation, anti-inflammatory, and anabolic action. We retrospectively reviewed a case series of 84 consecutive adult patients with KOA who underwent intra-articular injection of fresh fat derived SVF. Significant improvement in pain levels (NRS score decrease 3.5 +/- 1.1, p

Syphilis is a sexually transmitted disease caused by the spirochetes Treponema pallidum. Syphilitic spinal lesions present as erosive bone lesions often simulating spondylodiscitis or cancer. In this article we describe a rare case of cervical osteolytic lesion from tertiary syphilis. A 45-year-old male with axial neck pain, without fever presented with an isolated osteolytic lesion at C3. Tuberculous spondylitis was initially suspected. A new CT and contrast enhanced MRI of the cervical spine and of the neck showed an extention of the bone lesion at C3 with bilateral lymphadenomegaly. To confirm the diagnosis of tertiary syphilis, US-guided biopsy of the lymph nodes was performed. The patient was treated with i.m. benzylpenicillin 2.4 MIU and the follow-up showed clinical and radiological resolution of the condition. The aim of this case report is to raise awareness of tertiary syphilis in the differential diagnosis of lytic lesions of the spine among the spinal community.

Implantable intramedullary nail lengthening devices (e.g., PRECICE 2 system) have been proposed as alternative method to external fixation for lower limb lengthening surgery. The aim of this study was to analyse our outcomes and complications using the PRECICE 2 (P2) nail system and review them in light of the existing literature. A retrospective multicentre study was conducted on patients = 30 mm and a follow-up >= 6 months after the end of treatment. A total of 26 (15 males) patients were included, average age was 14.7 +/- 2.3 years; 26 nails (21 femur, 5 tibia) were implanted. The average goal lengthening was 49.4 +/- 12.4 mm, while average achieved lengthening was 44.4 +/- 11.6 mm. Average distraction and consolidation indexes were 11.9 +/- 2.1 days/cm and 25.1 +/- 8.1 days/cm, respectively. Nail accuracy and reliability were 91.1% and 88.5%, respectively. A total of five problems (joint contractures), one obstacle (femur fracture) and three complications (hip joint subluxation, deep infection and nail running back) were encountered. The P2 nail system is a valid alternative to external fixator for limb lengthening in young patients with no significant angular or rotation deformities. Our study confirms a favourable complication rate and available evidence from literature suggests a lower complication rate than external fixator systems. Nevertheless, surgeons should keep a watchful eye on risk of joint subluxation and mechanical complications with intramedullary lengthening.

Differential diagnosis of destructive osteolytic spinal lesions can be a diagnostic challenge. In this study, we described a rare case of spinal metastases from primary desmoplastic melanoma which had incorrectly been diagnosed and treated as tuberculous spondylodiscitis. An 82-year-old male patient with ongoing low back pain and a history of lumbar localized Pott’s performed a lumbar spine MRI that showed osteolytic lesion with first hypothesis of spondylodiscitis L2-L3. The patient was hospitalized and cause of worsening of the lumbar pain underwent a following series of non-diagnostic CT-guided and open lumbar biopsy at L2-L3 with unsuccessful antibiotic-antitubercular therapy. A new MRI revealed a worsening of previous lesions, extension of the osteolytic lesion at the level of L1-L2 and L3-L4 with neurological impairment. The diagnosis of metastatic melanoma was obtained with surgical decompression and open posterior biopsy procedure. The case described is pathognomonic of the difficulty in detecting the correct diagnosis in front of similar clinical and radiological manifestations. The presence of a previous Pott’s disease in the same involved vertebral site was of crucial importance in deflecting the correct diagnostic classification of the pathology, which was possible to ascertain only following an extensive biopsy sampling in the last surgery performed.

Study design: Retrospective analysis of a single institution prospective, longitudinal database of spinal pyogenic infections. Diagnosis of pyogenic spondylodiscitis (PS) can be challenging. Although presenting symptoms are often non-specific, acute non-remitting axial back pain is the most striking feature. Nevertheless, several authors have reported on the uncommon occurrence of patients with PS without axial back pain. The aim of this study was to characterize presenting symptoms, causative agents, comorbidities, and treatment outcomes of patients presenting with painless pyogenic spondylodiscitis. A total of 214 patients diagnosed with PS were reviewed, patients were divided into two groups: patients presenting with no axial back pain (no pain group, n = 16), and patients presenting with axial back pain (control group, n = 198). Analyzed data comprised general demographics, presenting symptoms, comorbidities, spinal infection location, and amount of spinal involvement. While average age (62.4 vs. 65.0) and sex distribution was similar between the two groups, a significant diagnostic delay was noted in the control group (53 vs. 17 days, p &lt, 0.001). Patients in the no pain group were more likely IV drug abusers or have had liver failure/cirrhosis. Anatomic distribution (i.e., cervical vs thoracolumbar) of the infection did not differ between the two groups, but a higher number of post-surgical infections was noted in the no pain group (37.5 vs. 15.6%, p = 0.026). E. coli and Pseudomonas spp. were more commonly seen in no pain group patients, and mortality was also higher in this group (12.5 vs. 6.0%, p = 0.004).

Lower limb deformities are very common in paediatric patients. Although most cases can be treated conservatively or with minimally invasive procedures (e.g., hemiepiphysiodesis), a minority of patients end up developing severe and multiaxial deformities. The most common causes of severe limb deformities in paediatric patient are congenital (e.g., fibular hemimelia or congenital proximal femur deficiency), post-traumatic (e.g., growth plate injuries), post-infectious (e.g., as a result of septic arthritis or osteomyelitis), and tumor or tumor-like conditions (e.g., Ollier’s disease, hereditary multiple exostoses). Correction of these deformities is of paramount importance to avoid long-term sequelae and later arthritis and pain. Hexapod external fixator, a later evolution of the original Ilizarov external fixator system, is specifically designed for simultaneous treatment of multiaxial deformities. In this chapter, we will be discussing specific aspects of the use of hexapod external fixator in paediatric patients; furthermore, several clinical cases will be presented in order to highlight critical steps in preoperative planning, surgery execution, postoperative care, and expected final results.

Study Design:Prospective observational cohort study.Objectives:To analyze clinical and economic results in patients with degenerative disc disease in the lumbar area for patients who received combined anterior and posterior fusion or total disc replacement (TDR).Methods:The study included 75 patients, 38 in the fusion group and 37 in the TDR group, who received either anterior/posterior fusion or TDR for lumbar disc disease from January 2005 to December 2008 with a minimum follow-up of 24 months. We collected data with regard to clinical parameters, demographics, visual analogue scale scores, Oswestry Disability Index scores, SF-36 and SF-6D data, surgery time, amount of blood loss, transfusion of blood products, number of levels, duration of hospital stay, and complications. For cost analysis, general infrastructure, theatre costs, as well as implant costs were examined, leading to primary hospital costs. Furthermore, average revision costs were examined, based on the actual data. Statistical analysis was performed using t tests for normal contribution and Mann-Whitney test for skew distributed values. The significance level was set to .05.Results:There was a higher surgery time, more blood loss, and longer hospital stay for the fusion group, compared with the TDR group. In addition, the hospital costs for the primary procedure and revision were 35% higher in the fusion group. The clinical data in terms of SF-36 and SF-6D showed no difference between these 2 groups.Conclusions:TDR is a good alternative to anterior and posterior lumbar fusion in terms of short follow-up analysis for clinical data and cost analysis. General advice cannot be given due to missing data for long-term costs in terms of surgical treatment of adjacent level or further fusion techniques.

Background The primary management of pyogenic spondylodiscitis is conservative. Once the causative organism has been identified, by blood culture or biopsy, administration of appropriate intravenous antibiotics is started. Occasionally patients do not respond to antibiotics and surgical irrigation and debridement is needed. The treatment of these cases is challenging and controversial. Furthermore, many affected patients have significant comorbidities often precluding more extensive surgical intervention. The aim of this study is to describe early results of a novel, minimally invasive percutaneous technique for disc irrigation and debridement in pyogenic spondylodiscitis. Materials and methods A series of 10 consecutive patients diagnosed with pyogenic spondylodiscitis received percutaneous disc irrigation and debridement. The procedure was performed by inserting two Jamshidi needles percutaneously into the disc space. Indications for surgery were poor response to antibiotic therapy (8 patients) and the need for more extensive biopsy (2 patients). Pre- and postoperative white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Oswestry disability index (ODI), and visual analogue score (VAS) for back pain were collected. Minimum follow-up was 18 months, with regular interval assessments. Results There were 7 males and 3 females with a mean age of 67 years. The mean WBC before surgery was 14.63 × 109/L (10.9–26.4) and dropped to 7.48 × 109/L (5.6–9.8) after surgery. The mean preoperative CRP was 188 mg/L (111–250) and decreased to 13.83 mg/L (5–21) after surgery. Similar improvements were seen with ESR. All patients reported significant improvements in ODI and VAS scores after surgery. The average hospital stay after surgery was 8.17 days. All patients had resolution of the infection, and there were no complications associated with the procedure. Conclusions Our study confirms the feasibility and safety of our percutaneous technique for irrigation and debridement of pyogenic spondylodiscitis. Percutaneous irrigation and suction offers a truly minimally invasive option for managing recalcitrant spondylodiscitis or for diagnostic purposes. The approach used is very similar to discography and can be easily adapted to different hospital settings. Level of Evidence Level III Electronic supplementary material The online version of this article (10.1186/s10195-018-0496-9) contains supplementary material, which is available to authorized users.

SummaryIntroduction Growth hormone deficiency is considered the most important factor determining skeletal fragility in hypopituitary patients. Osteoblasts and chondrocytes express growth hormone (GH) receptor. Two GH receptor isoforms (GHRi) have been identified: they differ for the presence/absence of a protein fragment encoded by exon 3 of GHR gene. Consequently, three genotypes were identified: carriers of both the full-length proteins (flfl-GHR), carriers of one full-length protein and one deleted protein (fld3-GHR) and carriers of both deleted proteins (d3d3-GHR). This polymorphism confers a higher sensitivity to endogenous GH and to recombinant human GH (rhGH); its effect on bone metabolism and skeletal fragility is unknown. The aim of this article was to investigate the role of GHRi in predicting skeletal fragility in adult-onset GHD (AO-GHD) patients. Subjects and methods A cross-sectional study was conducted to investigate the association between the d3-GHR isoform and the prevalence of morphometric vertebral fractures (VFs) in AO-GHD. Ninety-three AO-GHD were enrolled. Forty-nine patients carried flfl-GHRi (52·7%), and 44 patients (47·3%) carried at least one allele of the d3-GHR isoform. Thirty-two VFs were documented. Fifty-seven patients underwent rhGH replacement therapy. Results Median age was significantly higher in fractured patients as compared to nonfractured ones; d3-carrier patients showed a lower VF risk as compared to flfl-GHRi (OR: 0·37, 95% IC: 0·24–0·55, P < 0·0001). This finding was also confirmed in AO-GHD undergoing rhGH replacement therapy. Conclusion This study suggests that d3-GHR may protect AO-GHD particularly when treated with rhGH from the risk of VFs.

Intrathecal baclofen (ITB) therapy for spasticity has been suggested to accelerate the development of scoliosis. We present the case of a 17-year-old female patient with cerebral palsy who had ITB therapy from the age of 11 years. During this period, she developed a severe scoliosis measuring 86° from T11 to L4, with pain due to costo-pelvic impingement. Her baclofen pump had reached its end of life and required replacement if ITB therapy was to continue. This coincided with plans for scoliosis corrective surgery. METHODS: We performed scoliosis correction along with removal of baclofen pump and selective dorsal rhizotomy (SDR), as a single combined procedure. SDR was performed instead of ITB pump replacement for management of spasticity. RESULTS: Following surgery, scoliosis improved to 24°. At 6 month follow-up, there was significant improvement in spasticity and quality of life. CONCLUSIONS: This report illustrates the feasibility of a combined procedure to correct scoliosis and manage spasticity with SDR. We present the case details, our management and review of the published literature regarding the factors influencing treatment of scoliosis and spasticity.

We present the case of a 2-year-old child with Down′s syndrome who presented to our unit with torticollis. Imaging studies revealed the rare occurrence of anterior and posterior C1 arch defects, absent odontoid process, and atlantoaxial subluxation. We managed her conservatively for 3 years without neurological deficits or worsening of atlantoaxial subluxation. We discuss the rare occurrences of anterior and posterior arch defects of the atlas, the radiological presentations of axis defects in patients, and the occurrence of atlantoaxial instability in patients with Down′s syndrome. Management options with consideration to surgery in asymptomatic and symptomatic patients are also discussed.

Odontoid fractures account for 5% to 15% of all cervical spine injuries and 1% to 2% of all spine fractures. Type II fractures are the most common fracture pattern in elderly patients. Treatment (rigid and non-rigid immobilization, anterior screw fixation of the odontoid and posterior C1-C2 fusion) remains controversial and represents a unique challenge for the treating surgeon. The aims of treatment in the elderly is to quickly restore pre-injury function while decreasing morbidity and mortality associated with inactivity, immobilization with rigid collar and prolonged hospitalization. Conservative treatment of type II odontoid fractures is associated with relatively high rates of non-union and in a few cases delayed instability. Options for treatment of symptomatic non-unions include surgical fixation or prolonged rigid immobilization. In this report we present the case of a 73-year-old woman with post-traumatic odontoid non-union successfully treated with Teriparatide systemic anabolic therapy. Complete fusion and resolution of the symptoms was achieved 12 wk after the onset of the treatment. Several animal and clinical studies have confirmed the potential role of Teriparatide in enhancing fracture healing. Our case suggests that Teriparatide may have a role in improving fusion rates of C2 fractures in elderly patients.

As human lifespan increases so does the incidence of age-associated degenerative joint diseases, resulting in significant negative socioeconomic consequences. Osteoarthritis (OA) and intervertebral disc degeneration (IDD) are the most common underlying causes of joint-related chronic disability and debilitating pain in the elderly. Current treatment methods are generally not effective and involve either symptomatic relief with non-steroidal anti-inflammatory drugs and physical therapy or surgery when conservative treatments fail. The limitation in treatment options is due to our incomplete knowledge of the molecular mechanism of degeneration of articular cartilage and disc tissue. Basic understanding of the age-related changes in joint tissue is thus needed to combat the adverse effects of aging on joint health. Aging is caused at least in part by time-dependent accumulation of damaged organelles and macromolecules, leading to cell death and senescence and the eventual loss of multipotent stem cells and tissue regenerative capacity. Studies over the past decades have uncovered a number of important molecular and cellular changes in joint tissues with age. However, the precise causes of damage, cellular targets of damage, and cellular responses to damage remain poorly understood. The objectives of this review are to provide an overview of the current knowledge about the sources of endogenous and exogenous damaging agents and how they contribute to age-dependent degenerative joint disease, and highlight animal models of accelerated aging that could potentially be useful for identifying causes of and therapies for degenerative joint diseases.

PURPOSE: The aim of this study was to investigate postoperative changes in spinal sagittal alignment and postural balance in patients with hip-spine syndrome (HSS) and to verify whether any significant correlation exists between these changes and improvement of low back pain (LBP) symptoms following total hip replacement (THR) surgery. METHODS: Twenty-eight consecutive patients with HSS undergoing unilateral THR were prospectively enrolled. Whole spine X-rays were obtained before surgery and 6 months after surgery. The following parameters were measured: cervical lordosis, thoracic kyphosis, lumbar lordosis, pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (C7 SVA). Patients underwent pre- and postoperative postural balance assessment (950-460 BioSwayTM system; clinical test of sensory integration-CTSIB, limit of stability test-LOS) and patient reported outcome measures assessment (Short Form-36, SF-36, Oswestry Disability Index, ODI, Visual Analog Scale, VAS and Western Ontario and McMaster Universities Arthritis Index, WOMAC). RESULTS: Mean age of the patients was 61.7 ± 6.4. Median (interquartile range, IQR) pre-operative PI and PT were 50.0 (35.0, 60.0) and 11.0 (7.0, 23.0), respectively; lumbar lordosis was 49.0 (41.0, 68.0) and SVA 5.0 (-11.0, 41.0). No significant changes in sagittal alignment were observed postoperatively. Median LBP VAS decreased from 6.0 (5.0, 7.0) to 3.0 (2.0, 4.0) and ODI from 54.0 (39.0, 64.0) to 34.0 (26.0, 48.0) (p < 0.001). Median CTSIB improved from 1.22 (1.07, 1.45) to 1.01 (0.80, 1.19) and LOS from 46.0 (42.0, 58.0) to 37.0 (32.0, 39.0) postoperatively. No significant correlation was noted between postoperative changes in spinal sagittal alignment or postural balance and improvement of LBP VAS and ODI scores. CONCLUSIONS: Our study demonstrated an improvement in LBP levels (VAS and ODI) and postural balance in patients with HSS following THR surgery. No significant changes have been noted in radiographic spinal sagittal alignment postoperatively. The improvement in LBP levels does not correlate with post-operative changes in spinopelvic alignment or postural balance.

BACKGROUND CONTEXT: Tobacco smoking is a key risk factor for spine degeneration. However, the underlying mechanism by which smoking induces degeneration is not known. Recent studies implicate DNA damage as a cause of spine and intervertebral disc degeneration. Because tobacco smoke contains many genotoxins, we hypothesized that tobacco smoking promotes spine degeneration by inducing cellular DNA damage. PURPOSE: To determine if DNA damage plays a causal role in smoking-induced spine degeneration. STUDY DESIGN: To compare the effect of chronic tobacco smoke inhalation on intervertebral disc and vertebral bone in normal and DNA repair-deficient mice to determine the contribution of DNA damage to degenerative changes. METHODS: Two-month-old wild-type (C57BL/6) and DNA repair-deficient Ercc1(-/Δ) mice were exposed to tobacco smoke by direct inhalation (4 cigarettes/day, 5 days/week for 7 weeks) to model first-hand smoking in humans. Total disc proteoglycan (PG) content (1,9-dimethylmethylene blue assay), PG synthesis ((35)S-sulfate incorporation assay), aggrecan proteolysis (immunoblotting analysis), and vertebral bone morphology (microcomputed tomography) were measured. RESULTS: Exposure of wild-type mice to tobacco smoke led to a 19% increase in vertebral porosity and a 61% decrease in trabecular bone volume. Intervertebral discs of smoke-exposed animals also showed a 2.6-fold decrease in GAG content and an 8.1-fold decrease in new PG synthesis. These smoking-induced degenerative changes were similar but not worse in Ercc1(-/Δ) mice. CONCLUSIONS: Short-term exposure to high levels of primary tobacco smoke inhalation promotes degeneration of vertebral bone and discs. Disc degeneration is primarily driven by reduced synthesis of proteoglycans needed for vertebral cushioning. Degeneration was not exacerbated in congenic DNA repair-deficient mice, indicating that DNA damage per se does not have a significant causal role in driving smoke-induced spine degeneration. Published by Elsevier Inc.

Purpose To investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of DJK/DJF. Study design/setting This was a retrospective observational cohort study. Patient sample The sample included 40 patients who underwent posterior correction of SK from January 2006 to December 2014. Outcome measures Correlation analysis between the preoperative and postoperative spinopelvic alignment parameters and development of DJK over the course of the study period were studied. Methods Whole spine X-rays obtained before surgery, 3 months after surgery and at the latest follow-up were analyzed. The following parameters were measured: maximum of thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lower instrumented vertebra (LIV) and LIV plumb line. Development of DJK was considered as the primary end point of the study. The patient population was split into a control and DJK group, with 34 patients and 6 patients, respectively. Statistic analysis was performed using unpaired t test for normal contribution and Mann–Whitney test for skew distributed values. The significance level was set to 0.05. Results DJK occurred in 15% (n = 6) over the study period. There was a significantly lower postoperative TK for the group with DJK (42.4 ± 5.3 vs 49.8 ± 6.7, p = 0.015). LIV plumb line showed higher negative values in the DJK group (−43.6 ± 25.1 vs −2.2 ± 17.8, p = 0.0435). Furthermore, postoperative LL changes were lower for the DJK group (33.84 ± 13.86% vs 31.77 ± 14.05, p < 0.0001.) The age of the patients who developed DJK was also significantly lower than that of the control group (16.8 ± 1.7 vs 19.6 ± 4.9, p = 0.0024.) Conclusions SK patients who developed DJK appeared to have a significantly higher degree of TK correction and more negative LIV plumb line. In addition, there may be a higher risk for DJK in patients undergoing corrective surgery at a younger age.

Anterior cervical discectomy and fusion (ACDF) is a common surgical procedure for treatment of cervical radiculopathy and myelopathy due to cervical disc disease. Although it is a generally successful and safe procedure (complication rate between 2 and 4%), more recent studies have raised concerns regarding alterations of cervical spine biomechanics following a fusion. The fusion of a cervical segment leads to increased stress and loading on the adjacent segments which in turn can accelerate the degeneration process. Current estimates suggest that 25% of patients treated with ACDF will develop adjacent segment degeneration at 10 years (3% per year) and half of these patients will require new surgical intervention. Cervical disc arthroplasty (CDA) was developed as an alternative procedure to preserve motion both at the affected and adjacent levels and theoretically lower rates of adjacent segment degeneration. Prospective randomized trials comparing ACDF with CDA were initiated in 2000 and have demonstrated significant differences in some clinical outcome measures favouring CDA and comparable safety profiles between the two techniques. Following these trials many different devices have been licensed and are currently available on the market. The typical candidate patient for CDA is the young active adult patient with single level symptomatic disc disease and with intact posterior facet joints. The aim of this chapter is to critically review available literature supporting clinical use of CDA. Cervical disc replacement is nowadays an accepted technique with established short and medium-term follow-up data, however only long-term data will be able to confirm the promise of decreased adjacent segment disease and lower reoperation rate.

Pancreatitis is an inflammatory disease of the pancreas characterized by dysregulated activity of digestive enzymes, necrosis, immune infiltration, and pain. Repeated incidence of pancreatitis is an important risk factor for pancreatic cancer. Legumain, a lysosomal cysteine protease, has been linked to inflammatory diseases such as atherosclerosis, stroke, and cancer. Until now, legumain activation has not been studied during pancreatitis. We used a fluorescently quenched activity-based probe to assess legumain activation during caerulein-induced pancreatitis in mice. We detected activated legumain by ex vivo imaging, confocal microscopy, and gel electrophoresis. Compared with healthy controls, legumain activity in the pancreas of caerulein-treated mice was increased in a time-dependent manner. Legumain was localized to CD68+ macrophages and was not active in pancreatic acinar cells. Using a small-molecule inhibitor of legumain, we found that this protease is not essential for the initiation of pancreatitis. However, it may serve as a biomarker of disease, since patients with chronic pancreatitis show strongly increased legumain expression in macrophages. Moreover, the occurrence of legumain-expressing macrophages in regions of acinar-to-ductal metaplasia suggests that this protease may influence reprogramming events that lead to inflammation-induced pancreatic cancer.

Summary Objective To investigate the mechanisms by which chronic tobacco smoking promotes intervertebral disc degeneration (IDD) and vertebral degeneration in mice. Methods Three month old C57BL/6 mice were exposed to tobacco smoke by direct inhalation (4cigarettes/day, 5days/week for 6months) to model long-term smoking in humans. Total disc proteoglycan (PG) content [1,9-dimethylmethylene blue (DMMB) assay], aggrecan proteolysis (immunobloting analysis), and cellular senescence (p16INK4a immunohistochemistry) were analyzed. PG and collagen syntheses ( 35 S-sulfate and 3 H-proline incorporation, respectively) were measured using disc organotypic culture. Vertebral osteoporosity was measured by micro-computed tomography. Results Disc PG content of smoke-exposed mice was 63% of unexposed control, while new PG and collagen syntheses were 59% and 41% of those of untreated mice, respectively. Exposure to tobacco smoke dramatically increased metalloproteinase-mediated proteolysis of disc aggrecan within its interglobular domain (IGD). Cellular senescence was elevated two-fold in discs of smoke-exposed mice. Smoke exposure increased vertebral endplate porosity, which closely correlates with IDD in humans. Conclusions These findings further support tobacco smoke as a contributor to spinal degeneration. Furthermore, the data provide a novel mechanistic insight, indicating that smoking-induced IDD is a result of both reduced PG synthesis and increased degradation of a key disc extracellular matrix protein, aggrecan. Cleavage of aggrecan IGD is extremely detrimental as this results in the loss of the entire glycosaminoglycan-attachment region of aggrecan, which is vital for attracting water necessary to counteract compressive forces. Our results suggest identification and inhibition of specific metalloproteinases responsible for smoke-induced aggrecanolysis as a potential therapeutic strategy to treat IDD.

Background Context Surgical correction of Scheuermann kyphosis (SK) is challenging and plagued by relatively high rates of proximal junctional kyphosis and failure (PJK and PJF). Normal sagittal alignment of the spine is determined by pelvic geometric parameters. How these parameters correlate with the risk of developing PJK in SK is not known. Purpose The study aimed to investigate the relationship between preoperative and postoperative spinopelvic alignment and occurrence of PJK and PJF. Study Design/Setting This is a retrospective observational cohort study. Patient Sample The sample included 37 patients who underwent posterior correction of SK from January 2006 to December 2012. Outcome Measures The outcome measure was correlation analysis between preoperative and postoperative spinopelvic alignment parameters and the development of PJK over the course of the study period. Methods Whole spine x-rays obtained before surgery, 3 months after surgery, and at the latest follow-up were analyzed. The following parameters were measured: thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). The development of PJK was considered the primary end point of the study. Patient population was split into a control and a PJK group; repeated-measures analysis of variance was used to assess group and time differences. Results Seven patients developed PJK over the study period. Although the severity of the preoperative deformity (TK) did not differ significantly between the two groups, preoperative PI was significantly higher in the PJK group (51.9°C±8.6°C vs. 42.7°C±8.8°C, p=.018). Postoperative correction of TK was similar between the two groups (39.3% and 41.2%, p=.678) and final LL did not differ as well (53.6°C±9.2°C vs. 51.3°C±11.5°C). However, because PJK patients had larger preoperative PI values, a significant deficit of LL was observed at final follow-up in this group compared with the control group (ΔLL −10.5°C±9.8°C vs. 0.6°C±10.5°C, p=.013). Conclusions Scheuermann kyphosis patients who developed PJK appeared to have a significant postoperative deficit of LL ( lumbopelvic mismatch ). Lumbar lordosis decreases after surgery following correction of TK; therefore, TK correction should be planned according to preoperative PI values to avoid excessive reduction of LL in patients with higher PI values.

BACKGROUND CONTEXT: Currently, treatment for patients diagnosed with noncomplicated (ie, known infectious agent, no neurologic compromise, and preserved spinal stability) pyogenic spondylodiscitis (PS) is based on intravenous antibiotics and rigid brace immobilization. Since January 2010, we started offering our patients percutaneous posterior screw-rod instrumentation as an alternative approach to rigid bracing. Supposed benefits of posterior percutaneous instrumentation over rigid bracing are earlier free mobilization, increased comfort, and faster recovery. PURPOSE: To evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single-level PS and compare clinical and quality-of-life outcomes with standard thoracolumbosacral orthosis (TLSO) rigid bracing. STUDY DESIGN/SETTING: Retrospective observational cohort study. PATIENT SAMPLE: Twenty-seven patients consecutively diagnosed with single-level noncomplicated lower thoracic or lumbar PS from January 2010 to December 2011. OUTCOME MEASURES: Healing rate, healing time, and changes in segmental kyphosis Cobb angle were compared in the two treatment groups. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and complete blood count at regular time points until complete healing were also obtained. Self-report measures included Visual Analog Scale (VAS), Short-Form 12 (SF-12), and EuroQol five-dimension (EQ-5D) questionnaires. METHODS: At enrollment, patients were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and bridging posterior percutaneous screw-rod instrumentation followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy accordingly to isolated infectious agents. Patients were seen in the clinic at 1, 3, 6, and 9 months, and ESR, CRP, complete blood count, VAS, SF-12, and EQ-5D questionnaires were obtained. Segmental kyphosis was measured at diagnosis and at 9 months follow-up. Two-way repeated-measures analysis of variance was used to assess group and time differences across time points. RESULTS: Fifteen patients chose conservative treatment, whereas 12 patients chose surgical treatment. Complete infection healing was achieved in all patients with no significant differences in healing time (p

Intervertebral disc degeneration (IDD) is the leading cause of debilitating spinal disorders such as chronic lower back pain. Aging is the greatest risk factor for IDD. Previously, we demonstrated IDD in a murine model of a progeroid syndrome caused by reduced expression of a key DNA repair enzyme. This led us to hypothesize that DNA damage promotes IDD. To test our hypothesis, we chronically exposed adult wild-type (Wt) and DNA repair-deficient Ercc1(-/Δ) mice to the cancer therapeutic agent mechlorethamine (MEC) or ionization radiation (IR) to induce DNA damage and measured the impact on disc structure. Proteoglycan, a major structural matrix constituent of the disc, was reduced 3-5× in the discs of MEC- and IR-exposed animals compared to untreated controls. Expression of the protease ADAMTS4 and aggrecan proteolytic fragments was significantly increased. Additionally, new PG synthesis was reduced 2-3× in MEC- and IR-treated discs compared to untreated controls. Both cellular senescence and apoptosis were increased in discs of treated animals. The effects were more severe in the DNA repair-deficient Ercc1(-/Δ) mice than in Wt littermates. Local irradiation of the vertebra in Wt mice elicited a similar reduction in PG. These data demonstrate that genotoxic stress drives degenerative changes associated with IDD.

ObjectiveAcromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients.DesignA cross-sectional study was designed to investigate the association between the d3-GHR isoform and the prevalence of VFs in patients with acromegaly.MethodsIn this study, 109 acromegalic patients were included (M/F, 48/61): 73 with controlled/cured acromegaly and 36 with active disease. GHR genotype was assessed in each patient. All patients were evaluated for VFs and bone mineral density at lumbar spine and hip. Serum IGF1 levels and bone metabolism markers were measured. A multivariate analysis was performed to establish risk factors for VFs in our population.Resultsd3-GHR carriers showed an increased prevalence of VFs when compared with patients expressing full-length GHR (35/55 vs 12/54; PGHR deletion and VFs was demonstrated both in patients with active disease and in those with controlled/cured disease. Out of 35 patients who were prospectively evaluated, 13 (37.1%) developed incident VFs. The incidence of VFs was significantly higher in patients for whom the GHR gene has been deleted when compared with those harboring the fl gene (P=0.04). In multivariate analysis, male sex (odds ratio (OR), 3.250; P=0.041), IGF1 levels (OR, 1.183; P=0.031), length of active diseases (OR, 1.038; P=0.001), and d3-GHR genotype (OR, 3.060; P=0.015) were all confirmed as risk factors of VFs in our population.ConclusionsThis study suggests for the first time that exon 3 deletion of GHR may predispose patients with active and controlled acromegaly to a higher risk of VFs.

IntroductionLow back pain is a chronic health problem. It is the most common cause of limited activity. 90% of people worldwide will develop low back pain during their life. It is due, in the most ...

Summary The debate is still ongoing about the long term effects of the mininvasive vertebral augmentationtechniques and their usefulness in treating more complex cases where a bone inducing effect morethan a merely bone substitution would be suitable, such as the vertebral fractures in youngpatients. We previously developed a clinically relevant gene therapy approach using modifieddermal fibroblasts for inducing bone healing and bone formation in different animal models. Theaim of this study is to show the feasibility of a minimally invasive percutaneous intrasomatic exvivo gene therapy approach to treat thoracolumbar vertebral fractures and anterior column bonedefects in a goat model. Introduction Thoracolumbar fractures are more frequent in men (2/3) than in women (1/3) and peakbetween the ages of 20 and 40 years. (1) Approximately, 160 000 patients/year sustain aninjury of the spinal column in United States. (2) The most common mechanism of injury ofthe thoracolumbar spine involves flexion/distraction forces causing eccentric compression ofthe vertebral bodies and discs resulting in anterior wedge compression fractures.

The study design included a case report of Charcot spinal arthropathy treated with posterior and anterior spinal instrumentation. The objective of the study was to report an unusual case of Charcot spinal arthropathy as a late complication of traumatic spinal cord injury in a patient previously treated with a long posterior thoraco-lumbar instrumentation and postero-lateral fusion. A 33-year-old man with T10–T11 complete paraplegia presented with focal low back pain, kyphotic deformity of the lumbar region with L2–L3 fracture–dislocation and hardware failure. Our treatment consisted of a circumferential arthrodesis performed with a combined anterior and posterior approach. Spinal stabilization was achieved and the patient was pain free and able to resume a sitting posture. This report suggests that the development of a Charcot spine arthropathy must always be considered as a late complication of a spinal cord injury. Moreover, we would emphasize the fundamental role of a strict clinical and radiological follow-up in order to detect an early Charcot spine complication.

Introduction Osteoporosis is a highly prevalent and one of the most debilitating and costly chronic diseases worldwide and it is also responsible for approximately 1.5 million vertebral fragility fractures (VCFs) a year.1,2,3 Most of the patients experiencing an osteoporotic VCFs remain asymptomatic or minimally symptomatic; however, a large part of these patients do experience significant pain, resulting in decreased quality of life and disability and mortality too.4 The consequences of these fractures include pain and, in many cases, progressive vertebral collapse with resultant spinal kyphosis. Minimally invasive procedures, namely, kyphoplasty and vertebroplasty, represent a recent advance to the treatment of osteoporotic VCFs.5,6,7 The aim of this study is to compare effects in terms of recovery and quality of life and to compare deformity prevention efficacy of kyphoplasty and conservative treatment in postmenopausal women with an osteoporotic VCF. The aim of this study is to provide an efficacy assessment of kyphoplasty as compared with standard conservative treatment in postmenopausal women (bracing immobilization).8,9,10 Patients and Methods We designed a retrospective case–control study on 110 postmenopausal women. Included in this study were patients who were diagnosed with postmenopausal osteoporosis according to National Osteoporosis Foundation (NOF) guidelines, with a recent (Results Kyphoplasty-treated patients had lower back pain VAS scores at 1 month as compared with conservatively treated patients ( p Conclusion Kyphoplasty seems to be a safe and effective procedure in reducing back pain due to painful VCF. The kyphosis restoring effect is also extremely interesting and can be achieved only in the first days after fracture time. In conclusion, kyphoplasty is a procedure that offers a fast recovery and a better quality of life at 1 month after treatment, helping restoring segmental kyphosis after VCFs.11,12,13 Acknowledgments There was no external funding source and no funding source played a role in the investigation. References Who are candidates for prevention and treatment for osteoporosis? Osteoporos Int 1997;7(1):1–6 Johnell O, Kanis JA. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 2006;17(12):1726–1733 Iqbal MM, Sobhan T. Osteoporosis: a review. Mo Med 2002;99(1):19–24 Gold DT. The clinical impact of vertebral fractures: quality of life in women with osteoporosis. Bone 1996;18(3, Suppl):185S–189S Jarvik JG, Kallmes DF. Point of view. Efficacy of vertebroplasty and kyphoplasty. Spine 2009;34(6):613–614 Kallmes DF, Comstock BA, Heagerty PJ, et al. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009;361(6):569–579 Weinstein JN. Balancing science and informed choice in decisions about vertebroplasty. N Engl J Med 2009;361(6):619–621 Lyritis GP, Mayasis B, Tsakalakos N, et al. The natural history of the osteoporotic vertebral fracture. Clin Rheumatol 1989;8(2, Suppl 2):66–69 Prather H, Watson JO, Gilula LA. Nonoperative management of osteoporotic vertebral compression fractures. Injury 2007;38(3, Suppl 3):S40–S48 Garfin SR, Yuan HA, Reiley MA. New technologies in spine: kyphoplasty and vertebroplasty for the treatment of painful osteoporotic compression fractures. Spine 2001;26(14):1511–1515 Ledlie JT, Renfro M. Balloon kyphoplasty: one-year outcomes in vertebral body height restoration, chronic pain, and activity levels. J Neurosurg 2003;98(1, Suppl):36–42 Voggenreiter G. Balloon kyphoplasty is effective in deformity correction of osteoporotic vertebral compression fractures. Spine 2005;30(24):2806–2812 Pradhan BB, Bae HW, Kropf MA, Patel VV, Delamarter RB. Kyphoplasty reduction of osteoporotic vertebral compression fractures: correction of local kyphosis versus overall sagittal alignment. Spine 2006;31(4):435–441

Introduction Reactive oxygen species (ROS) and free radicals are byproducts of oxidative metabolism that cause cellular damage and are implicated in the pathogenesis of age-related diseases. Mitochondria are the main cellular sites of ROS production. Recent studies reported a positive correlation between mitochondria dysfunction and age-associated disk cellular senescence and apoptosis. Hence, we hypothesize that reducing mitochondria-generated ROS would slow the onset of age-related intervertebral disk degeneration (IDD). We tested this hypothesis by chronically treating the Errc1-/D mouse model of accelerated aging with XJB-5-131, a mitochondria-targeted free radical scavenger previously demonstrated to be therapeutic in rodent models of hemorrhagic shock and sepsis. Materials and Methods Pairs of 5-week-old siblings of Ercc1-/▵ mice were treated with XJB-5-131 or oil carrier control (intraperitoneal injections, 2 mg/Kg, 3×/week, 15 weeks). Total proteoglycan content (safranin-O histology, DMMB assay) and synthesis (35S-sulfate incorporation) were measured. Transmission electron microscopy (TEM) was performed to assess disk mitochondria number and morphology in Ercc1-/▵ mice and wild-type littermates. Results TEM showed greater mitochondrial death in discs of Ercc1-/▵ mice compared to their wild-type littermates. Compared to oil-treated Ercc1-/▵ controls, disks from XJB-5-131 treated Ercc1-/▵mice showed greater (1.3×) proteoglycan matrix content and higher (1.9×) rate of proteoglycan synthesis. Conclusion Errc1-/Dmouse model of a human progeria had previously established as an accurate model of spine aging. Treatment of Errc1-/Dmice with a mitochondria-targeted ROS scavenger decreased disk proteoglycan loss. This result is consistent with our in vitro studies which showed XJB-5-131 is able to rescue reduced proteoglycan synthesis mediated by oxidative stress in human disk cells grown at high oxygen (20 vs. 5% oxygen). The findings in this study suggest that oxidative damage originating from mitochondria dysfunction plays an important role in disk health. The mitochondrial-targeted ROS free radical scavenger XJB-5-131 is potentially therapeutic in delaying the onset of age-related IDD. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared

Background Standard laminectomy for treatment of cervical myelopathy is associated with secondary instability and kyphosis, while laminectomy combined with fusion puts adjacent segments at risk of degeneration. Single- and double-door laminoplasty techniques have been developed to overcome these limitations. More recently, complications related to bone graft dislodgment have fostered development of hardware-augmented laminoplasty techniques. The aim of this study is to review the clinical safety and effectiveness of a newly developed technique of instrumented French-door laminoplasty for treatment of cervical myelopathy. Materials and methods A series of 25 consecutive myelopathic patients were treated with a novel instrumented cervical French-door laminoplasty technique, whereby the enlarged posterior arch was held open with maxillofacial plates and screws. Patients had pre- and postoperative assessments with the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) Score, Visual Analogue Score and radiographs. Minimum follow-up was 40 months, with regular interval assessments. Results There were 18 males with a mean age of 45 years. The mean operative time was 145 min. The average hospital stay was 2.4 days and the mean follow-up was 56.5 months (40–72). All patients reported neurological improvements and there was a 35% improvement in NDI, and JOA score improved by 4.8 points. No postoperative hardware-related complications were noted and only one case of temporary C5 palsy, which completely resolved by the one-year follow-up. Conclusions Our data and clinical experience demonstrate that this hardware-augmented laminoplasty technique is safe and effective. We observed no hardware-related complications in our series. The use of readily available maxillofacial titanium miniplates and ease of surgical procedure means that this technique can be easily adopted into clinical practice. Level of evidence Level IV.

Background Timing of surgery and the importance of the size of disc prolapse in cauda equina syndrome (CES) remain controversial. Objective To investigate whether there is a relationship between postoperative urinary function, preoperative duration of neurogenic lower urinary tract dysfunction (NLUTD), and the level of canal compromise. Methods Seventy-one patients operated for CES were prospectively identified between 2010 and 2013. Fifty-two cases with preoperative NLUTD were included. The "Prolapse: Canal ratio" (PCR) was calculated as a proportion of cross-sectional area of disc prolapse on total cross-sectional area of spinal canal. Results Median of preoperative duration of NLUTD was 72 h (48; 132) and period from first assessment to surgery 10.5 h (7; 18.5). Urinary incontinence was seen in 46.2% of patients, 38.4% had painless retention and 15.4% had painful retention. In 38.5% of cases, urinary symptoms persisted for more than 20 mo postoperatively. There was no correlation between duration of preoperative NLUTD and urinary dysfunction persistence (P = .921). The outcome was not significantly influenced by having surgery more than the 48 h after presentation (P = .135). Preoperative incontinence persisted in 58% and painless retention in 30% of cases. The mean PCR was 0.6 ± 0.18. There was no correlation between PCR and outcome (P = .537) even after adjusting for duration of preoperative NLUTD (P = .7264). Conclusion No significant correlation was demonstrated between the preoperative duration of urinary dysfunction, the size of disc herniation relative to size of spinal canal, and postoperative urinary function in a large consecutive series of patients with CES.