A systems-biology approach connects aging mechanisms with Alzheimer's disease pathogenesis.

Age is the strongest risk factor for developing Alzheimer's disease, the most common neurodegenerative disorder. However, the mechanisms connecting advancing age to neurodegeneration in Alzheimer's disease are incompletely understood. We conducted an unbiased, genome-scale, forward genetic screen for age-associated neurodegeneration in Drosophila to identify the underlying biological processes required for maintenance of aging neurons. To connect genetic screen hits to Alzheimer's disease pathways, we measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer's disease. We further identified Alzheimer's disease human genetic variants that modify expression in disease-vulnerable neurons. Through multi-omic, multi-species network integration of these data, we identified relationships between screen hits and tau-mediated neurotoxicity. Furthermore, we computationally and experimentally identified relationships between screen hits and DNA damage in Drosophila and human iPSC-derived neural progenitor cells. Our work identifies candidate pathways that could be targeted to attenuate the effects of age on neurodegeneration and Alzheimer's disease.

Constructing and evaluating caspase-activatable adeno-associated virus vector for gene delivery to the injured heart.

Adeno-associated virus (AAV) is a promising vector for gene therapy, but its broad tropism can be detrimental if the transgene being delivered is harmful when expressed ubiquitously in the body, i.e. in non-target tissues. Delivering the transgene of interest to target cells at levels high enough to be therapeutically effective while maintaining safety by minimizing delivery to off-target cells is a prevalent challenge in the field of gene therapy. We have developed a protease activatable vector (provector) platform based on AAV9 that can be injected systemically to deliver therapeutic transgenes site-specifically to diseased cells by responding to extracellular proteases present at the disease site. The provector platform consists of a peptide insertion into the virus capsid which disrupts the virus' ability to bind to cell surface receptors. This peptide contains a blocking motif (aspartic acid residues) flanked on either side by cleavage sequences that are recognized by certain proteases. Exposure to proteases cleaves the peptides off the capsid, activating or "switching ON" the provector. In response to the activation, the provectors regain their ability to bind and transduce cells. Here, we have designed a provector that is activated by cysteine aspartic proteases (caspases), which have roles in inflammation and apoptosis and thus are elevated at sites of diseases such as heart failure, neurodegenerative diseases, and ischemic stroke. This provector demonstrates a 200-fold reduction in transduction ability in the OFF state compared to AAV9, reducing the virus' ability to transduce off-target healthy tissue. Following exposure to and proteolysis by caspase-3, the provector shows a 95-fold increase in transduction compared to the OFF state. The switchable transduction behavior was found to be a direct result of the peptide insertion ablating the ability of the virus to bind to cells. In vivo studies were conducted to characterize the biodistribution, blood circulation time, neutralizing antibody formation, and targeted delivery ability of the caspase-activatable provector in a model of heart failure.

Dorsal Epidural Gas after Lumbar Microdiskectomy Treated with CT-guided Needle Aspiration.

To present a case of unusual dorsal epidural gas (EG) accumulation after a simple lumbar microdiskectomy (MD), treated with computed tomography (CT)-guided needle aspiration. A 78-year-old woman underwent simple lumbar MD at the L3-4 level. One week after the operation, the patient complained of severe back pain radiating to the right thigh. Follow-up magnetic resonance imaging (MRI) and CT revealed huge EG formation at the dorsal L3-4 epidural space. Conservative treatment did not resolve the patient's pain. We performed CT-guided needle aspiration after 1 week of conservative treatment. The patient's pain fully resolved after aspiration, but it recurred 1 week later. Follow-up MRI and CT revealed re-accumulation of the dorsal EG at the L3-4 level. CT-guided needle aspiration was repeated, again leading to full pain resolution. Follow-up CT 6 months after the second aspiration showed no recurrent dorsal EG. The patient has been symptom-free for 1 year since the second aspiration. CT-guided needle aspiration is a safe and effective alternative to re-operation in the context of dorsal EG formation after MD.

An essential N-terminal serine-rich motif in the AAV VP1 and VP2 subunits that may play a role in viral transcription.

Adeno-associated virus (AAV) is one of the most researched, clinically utilized gene therapy vectors. Though clinical success has been achieved, transgene delivery and expression may be hindered by cellular and tissue barriers. Understanding the role of receptor binding, entry, endosomal escape, cytoplasmic and nuclear trafficking, capsid uncoating, and viral transcription in therapeutic efficacy is paramount. Previous studies have shown that N-terminal regions of the AAV capsid proteins are responsible for endosomal escape and nuclear trafficking, however the mechanisms remain unknown. We identified a highly-conserved three-residue serine/threonine (S/T) motif in the capsid N-terminus, previously uncharacterized in its role in intracellular trafficking and transduction. Using alanine scanning mutagenesis, we found S155 and the flanking residues, D154 and G158, are essential for AAV2 transduction efficiency. Remarkably, specific capsid mutants show a 5 to 9-fold decrease in viral mRNA transcripts, highlighting a potential role of the S/T motif in transcription of the viral genome.

A Versatile Adeno-Associated Viral Vector Cross-Linking Platform Capable of Tuning Cellular Tropisms and Simultaneously Inducing Solid-Phase Gene Delivery.

Developing gene carriers with improved affinities for target cells and the simultaneous diversification of their delivery modes will be pivotal for upgrading gene therapy technologies. In this study, a simple and versatile adeno-associated virus (AAV) conjugation platform using the cross-linker 3,3'-dithiobis(sulfosuccinimidyl propionate) (DTSSP) is proposed. Depending on the quantity of the DTSSP molecules, the AAV-DTSSP complexes could either be linked with the relevant biomolecules for altering cellular tropisms or further form a self-assembled AAV-DTSSP pellet capable of mimicking a polymeric gene delivery system. At lower quantities of DTSSP, the AAV-DTSSP complexes were conjugated with aminated l-fucose molecules, whose levels are typically upregulated in pancreatic cancer cells, resulting in enhanced gene delivery efficiencies in pancreatic cancer cells. At higher concentrations of DTSSP, visible solid forms of the AAV-DTSSP pellets were formed, and the AAV pellets demonstrated the capability to induce a localized, sustained gene expression pattern comparable to that of conventional biomaterial-based approaches. Thus, a multipurpose AAV cross-linking platform, which can enable AAV vector systems that are capable of altering cellular tropisms and simultaneously inducing solid-phase delivery, will provide crucial insights into vector design for further upgrading of gene delivery technologies.

Motor palsy after posterior cervical foraminotomy: anatomical consideration.

BACKGROUND: Motor palsy is a serious complication that can result from cervical surgery. We introduced cases of motor palsy after posterior cervical foraminotomy (PCF) and consider cervical anatomy. METHODS: Between January 2007 and August 2010, 133 PCFs were performed on 106 consecutive patients with radiculopathy caused by foraminal stenosis or posterolateral disc herniation. RESULTS: Three of 133 (2.3%) levels that underwent PCF developed a motor palsy. Two cases involved the C5 nerve root, and one case involved the C6 nerve root. The cause of the C5 palsy may have been excessive retraction, whereas the cause of the C6 palsy may have been thermal damage caused by drilling. The rate of C5 palsy (22.2%) was much higher than that seen with other nerves. Anatomically, the C5 nerve root is thinner and covers the entire intervertebral disc at a relatively sharper angle than the other nerve roots. The removal of an extruded disc at C4-5 forces more excessive retraction of the C5 nerve root. CONCLUSIONS: Although PCF is a good alternative treatment with minimal morbidity for cervical radiculopathy, surgeons should keep in mind the possibility of motor palsy, especially at C4-5.

Laser-assisted posterior cervical foraminotomy and discectomy for lateral and foraminal cervical disc herniation.

OBJECTIVE: Posterior cervical foraminotomy and discectomy (PCFD) is regarded as an effective treatment option for cervical radiculopathy. However, limited exposure of the disc space is one of its major disadvantages. To address this problem, we used a CO(2) laser for sophisticated decompression. The purpose of this study was to demonstrate the clinical outcomes of laser-assisted PCFD and to discuss the benefits of laser use. METHODS: A total of 47 consecutive patients with cervical radiculopathy were treated with PCFD. Among them, 24 patients were treated with laser-assisted PCFD, and the remaining 23 patients were treated with conventional PCFD. After standard posterior cervical microscopic foraminotomy, a microscopic CO(2) laser was used for selective discectomy in the laser PCFD group. Clinical data were compared with a minimum 2-year follow-up period. Clinical outcomes were evaluated using the visual analogue scale (VAS), Neck Disability Index (NDI), and modified MacNab criteria. RESULTS: The clinical outcomes of the two groups were similar. The mean VAS score for radicular arm pain improved from 7.42 to 1.83 in the laser PCFD group and from 8.30 to 1.65 in the conventional PCFD group. The mean NDI improved from 47.00% to 10.46% in the laser PCFD group and from 53.86% to 10.02% in the conventional PCFD group. The rate of excellent or good outcomes was 87.5% for the laser PCFD group and 86.9% for the conventional PCFD group. A significant difference between the groups was found for intraoperative bleeding. The laser PCFD group had significantly lower estimated blood loss values than did the conventional PCFD group (p<0.05). CONCLUSIONS: Laser-assisted PCFD is an efficacious surgical option for treating lateral cervical disc herniation. The pinpoint accuracy of the laser scalpel facilitates sophisticated decompression within a limited surgical field, and may reduce the risk of intraoperative bleeding and neural damage.

Rapid progression of spinal epidural lipomatosis.

Spinal epidural lipomatosis (SEL) is a rare but well-recognized condition. In general, the onset of its symptoms is insidious and the disease progresses slowly. We report two cases of rapid progression of SEL with no history of steroid intake in non-obese individuals after epidural steroid injection. These SEL patients developed neurologic symptoms after less than 5 months; these symptoms were confirmed to be due to SEL by serial MR images. After the debulking of the epidural fat, their symptoms improved.

Changes in back pain after percutaneous endoscopic lumbar discectomy and annuloplasty for lumbar disc herniation: a prospective study.

OBJECTIVE: Percutaneous endoscopic lumbar discectomy and annuloplasty (PELDA) is a minimally invasive spinal technique for lumbar disc herniation. Following discectomy, the relief of leg pain is common; however, the relief of back pain is less predictable. The purpose of this study was to evaluate changes in back pain and to examine the predisposing factors for postoperative back pain following PELDA. DESIGN: In this prospective study, 58 patients with leg and back pain associated with disc herniation underwent PELDA. The patients were divided into two groups: unfavorable and favorable. Patients were defined as having unfavorable outcomes if the percentage improvement of back pain <50% or the postoperative Oswestry Disability Index (ODI) >20% at postoperative 24 months. The preoperative demographic, clinical, and radiologic factors for each group were statistically analyzed. RESULTS: Fifty-two patients were enrolled in this study. The mean visual analog scale scores for back pain and the ODI scores significantly improved from 6.6 and 55.9% preoperatively to 2.5 and 12.7% at the 24-month follow-up. The surgical satisfaction rate was 78.4% at the final follow-up. Eighteen (34.6%) patients had unfavorable outcomes. Patients with advanced disc degeneration of operative levels had significantly worse outcomes than those with mild disc degeneration (odds ratio: 6.316, 95% confidence interval 1.25-31.86, P < 0.05). The severity of postoperative back pain was negatively correlated with surgical satisfaction (correlation coefficient: -0.564, P = 0.00). CONCLUSION: PELDA can relieve back pain as well as leg pain through direct decompression and thermal ablation of the annular defect. Disc degeneration can be expected to influence clinical outcomes following PELDA.

Failed anterior lumbar interbody fusion due to incomplete foraminal decompression.

BACKGROUND: Anterior lumbar interbody fusion (ALIF) has gained widespread popularity for spinal disorders requiring fusion. The purpose of this study was to analyze ALIF failures. METHODS: The medical records of 223 patients treated with ALIF between January 2007 and June 2008 were retrospectively reviewed. Patients with unfavorable outcomes, including subsequent posterior decompression at the index level or poor outcomes after ALIF were identified based on clinical and radiological findings. The patients were divided into two groups: an unfavorable group and a favorable group. Preoperative clinical and radiological factors for each group were statistically analyzed. RESULTS: Two hundred of the 223 patients were enrolled in this study. Thirteen (6.5%) of 200 patients resulted in unfavorable outcome. Four patients (2%) of them underwent posterior decompressive surgery. The main cause of unfavorable outcomes was incomplete decompression of the foraminal stenosis. Unfavorable outcomes were obtained in patients with the level of L5-S1 (p = 0.036), higher body mass index (p = 0.048), higher percentage of slippage (p = 0.024), and severe facet arthropathy (p = 0.013). However, there was no difference in preoperative disc height, foraminal size, facet angle, facet tropism, or preoperative visual analog scale for back and leg pain, the Oswestry disability index, symptom duration, and fusion rate between the two groups. CONCLUSION: Based on these results, posterior decompression and fusion may be considered for obese patients with the level of L5-S1, high-grade spondylolisthesis, or severe facet arthropathy. On the other hand, ALIF can be used an effective alternative treatment in many spinal disorders requiring fusion.

Comparison study of the instrumented circumferential fusion with instrumented anterior lumbar interbody fusion as a surgical procedure for adult low-grade isthmic spondylolisthesis.

BACKGROUND: Instrumented circumferential fusion has been used as a primary and salvage procedure in lumbar spine fusion, especially for adult low-grade isthmic spondylolisthesis. Recently, instrumented anterior lumbar interbody fusion (ALIF) has been shown to provide good clinical and radiologic results that are comparable with those attained with traditional lumbar fusion. However, there have been no reports available that compare instrumented circumferential fusion with instrumented ALIF. METHODS: Between January 2003 and November 2004, a total of 43 consecutive patients underwent instrumented ALIF (group I) at one hospital of the authors. Between February 2003 and October 2006, a total of 32 consecutive patients underwent instrumented circumferential fusion (group II) at the other hospital of the authors. The authors retrospectively reviewed clinical and radiologic data from patients. The time spent on the operation, blood loss, blood transfusions, the length of hospital stay, complications, clinical results, and radiologic results, including disc height (DH), degree of listhesis, segmental lordosis (SL), and whole lumbar lordosis (WL), were analyzed and compared. Clinical outcomes were graded using visual analog scale (VAS) scores. Functional outcomes were measured using Oswestry Disability Index (ODI) scores and return-to-work status. RESULTS: The mean follow-up period was 41.1 and 32.9 months in group I and group II, respectively. Radiologic evidence of fusion was noted in 42 of 43 patients in group I and in 32 of 32 patients in group II. In both groups, all of the radiologic data, including the DH, degree of listhesis, SL, and WL significantly changed from the preoperative to postoperative period except for WL in group II. In both groups, VAS scores for back and leg pain and ODI scores significantly changed from the preoperative to postoperative period. There was no significant difference for VAS scores for back ODI scores in the two treatment groups after surgery. The mean time until return to work was 3.7 months in group I and 3.6 months in group II (p < .05). The mean hospital stay for group I (7.4 days) was shorter than that for group II (15.2 days) (p < .05). The mean operation time in group I (190 minutes) was shorter than that in group II (260.8 minutes) (p < .05). The mean blood loss in group I (300 mL) was less than that in group II (379 mL) (p < .05). CONCLUSIONS: According to the present clinical outcome, instrumented ALIF is at least as effective as instrumented circumferential fusion for the treatment of back pain in adult patients with low-grade isthmic spondylolisthesis. Moreover, in terms of operative data including the duration of operation and hospital stay, as well as blood loss, instrumented ALIF demonstrates better results.

Surgical site infection in spinal surgery: detection and management based on serial C-reactive protein measurements.

OBJECT: C-reactive protein (CRP) is a well-known sensitive laboratory parameter that shows an increase within 6 hours after the onset of bacterial infection. In relation to surgery, a normal CRP response is a rapid increase followed by a gradual reduction, eventually returning to the normal range. The goal of this study was to determine the diagnostic significance of CRP as a detector for early onset surgical site infection in spinal surgery and to discuss effective medical treatment through clinical interpretation and application of the measured CRP values. METHODS: A prospective study was performed in 348 consecutive cases involving patients who underwent spinal surgery under general anesthesia between February and September 2008. Blood samples were obtained preoperatively and on postoperative Days 1, 3, and 5 in patients undergoing single-level decompression surgery. An additional blood specimen was obtained at postoperative Day 7 in patients requiring more extensive surgeries. Recorded laboratory results were compared with the patients' clinical course to determine the diagnostic significance of CRP. All of the patients received intravenous prophylactic antibiotic therapy. Once an abnormal response of CRP, indicated by a tendency toward continuous elevation, was noted on Day 5 or Day 7, the prophylactic antibiotics were replaced with another regimen and administration was resumed along with careful observation for signs of surgical site infection. RESULTS: Monitoring of CRP revealed a characteristic increase and decrease pattern in 332 of 348 patients (95.4%) showing a normal clinical course with regard to early infectious complications. The mean measured CRP (reference range < 4 mg/L) averaged 14.9 +/- 20.3 mg/L on Day 1, 15.4 +/- 25.1 mg/L on Day 3, and 7.9 +/- 13.3 mg/L on Day 5. In contrast, there were 16 cases (4.6%) of abnormal CRP responses resulting in the resumption of intravenous antibiotic treatment, which included a second rise (in 12 cases) and a steady rise (in 4) in the CRP value. Five (1.4%) of 16 patients experienced infectious complications related to spinal surgery. Three patients (0.9%) received long-term antibiotic therapy for 4-6 weeks; however, all patients recovered with medical treatment alone and did not experience gross wound disruption or subsequent discitis. As a predictor for early wound infection, the sensitivity, specificity, positive predictive value, and negative predictive value for abnormal CRP responses were calculated as 100%, 96.8%, 31.3%, and 100%, respectively. CONCLUSIONS: The above results demonstrate that CRP screening is a simple and reliable test for the detection of early infectious complications after spinal surgery. Close observation and appropriate medical management should be performed in a timely fashion when abnormal CRP responses are observed at 5 or 7 days after surgery.

Mini-transforaminal lumbar interbody fusion versus anterior lumbar interbody fusion augmented by percutaneous pedicle screw fixation: a comparison of surgical outcomes in adult low-grade isthmic spondylolisthesis.

STUDY DESIGN: Retrospective clinical data analysis. OBJECTIVE: To compare clinical results with radiologic results of 2 fusion techniques for adult low-grade isthmic spondylolisthesis. SUMMARY OF BACKGROUND DATA: There is clear evidence that lumbar interbody fusion using anterior and posterior approaches provides a high fusion rate, good sagittal alignment, and good clinical outcomes. However, there are no recent studies that compare these 2 fusion techniques. METHODS: Between March 2004 and December 2004, 48 patients underwent instrumented mini-anterior lumbar interbody fusion (ALIF) and 46 underwent instrumented mini-transforaminal lumbar interbody fusion (TLIF). The mean follow-up periods were 32.6 and 29.7 months, respectively. RESULTS: The mean visual analog scale (VAS) scores for back and leg pain decreased, respectively, from 7.7 and 7.5 to 2.9 and 2.7 in the ALIF group and from 7.0 and 6.3 to 2.3 and 2.2 in the TLIF group. The mean Oswestry disability index (ODI) scores improved from 51.4% to 23.2% in the ALIF group and from 52% to 14.4% in the TLIF group. In both groups, the VAS and ODI scores significantly changed preoperatively to postoperatively (P<0.001). However, statistical analysis showed no significant difference in postoperative VAS/ODI scores between groups. Radiologic evidence of fusion was noted in 95.8% and 92.3% of the patients in the ALIF group and the TLIF group, respectively. In both the groups, changes in the disc height, segmental lordosis, degree of listhesis, and whole lumbar lordosis (WL) between the preoperative and postoperative periods were significant except for WL in the TLIF group. The amount of change between preoperative and postoperative disc height, segmental lordosis, and WL demonstrated significant intergroup differences (P<0.05). CONCLUSIONS: The mini-ALIF group demonstrated key radiographic advantages compared with the mini-TLIF group for adult low-grade isthmic spondylolisthesis. However, clinical and functional outcomes did not demonstrate significant differences between groups.

An analysis of general surgery-related complications in a series of 412 minilaparotomic anterior lumbosacral procedures.

OBJECT: Anterior lumbar surgery is associated with certain perioperative visceral and vascular complications. The aim of this study was to document all general surgery-related adverse events and complications following minilaparotomic retroperitoneal lumbar procedures and to discuss strategies for their management or prevention. METHODS: The authors analyzed data obtained in 412 patients who underwent anterior lumbosacral surgery between 2003 and 2005. The series comprised 114 men and 298 women whose mean age was 56 years (range 34-79 years). Preoperative diagnoses were as follows: isthmic spondylolisthesis (32%), degenerative spondylolisthesis (24%), instability/stenosis (15%), degenerative disc disease (15%), failed-back surgery syndrome (7%), and lumbar degenerative kyphosis or scoliosis (7%). A single level was exposed in 264 patients (64%), 2 in 118 (29%), and 3 or 4 in 30 (7%). The average follow-up period was 16 months. RESULTS: Overall, 52 instances of complications and adverse events occurred in 50 patients (12.1%), including sympathetic dysfunction in 25 (6.06%), vascular injury repaired with/without direct suture in 12 (2.9%), ileus lasting > 3 days in 5 (1.2%), pleural effusion in 4 (0.97%), wound dehiscence in 2 (0.49%), symptomatic retroperitoneal hematoma in 2 (0.49%), angina in 1 (0.24%), and bowel laceration in 1 patient (0.24%). There was no instance of retrograde ejaculation in male patients, and most complications had no long-term sequelae. CONCLUSIONS: This report presents a detailed analysis of complications related to anterior lumbar surgery. Although the incidence of complications appears low considering the magnitude of the procedure, surgeons should be aware of these potential complications and their management.

An evaluation of vascular anatomy for minilaparotomic anterior L4-5 procedures.

OBJECT: The complexity of the vascular anatomy pertinent to the L4-5 intervertebral disc space has led to difficulties when performing the anterior approach to the lumbar spine. The purpose of the present study was to evaluate the variations of the great vessels to match the imaging-documented axial anatomy with the surgical exposure. METHODS: The authors analyzed data obtained in 223 patients who had undergone mini-open anterior lumbar surgery involving the L4-5 disc. The preoperative magnetic resonance images or computed tomography scans were evaluated by examiners blinded to the surgical approach to determine the vascular configuration. All complications of the procedures were described. Two major variations of the vascular configuration were delineated according to the location of the bifurcation of the inferior vena cava. On images showing the lower margin of the L-4 vertebra, the anatomy in 182 patients (81%) was classified as Type A because the inferior vena cava (IVC) was not bifurcated; in 38 patients (17%) it was classified as Type B because the IVC was bifurcated. Type A could be subdivided into Types A1 and A2 according to whether the aorta was bifurcated (A2) or not (A1) on the same image. The surgical exposure used was above the bifurcations (in Type A) and below the bifurcations (in Type B). The major complications were three venous injuries, and the leading complication was sympathetic dysfunction in 14 patients, which in most cases resolved spontaneously. CONCLUSIONS: Careful preoperative evaluation of the vascular anatomy is essential to conducting successful anterior lumbar surgery. The determination of an appropriate approach can contribute to a reduction of unnecessary vascular retraction and a consequent decrease in vascular complications.

Revision surgery of the lumbar spine: anterior lumbar interbody fusion followed by percutaneous pedicle screw fixation.

OBJECT: The aim of this study was to evaluate the efficacy of anterior lumbar interbody fusion (ALIF) augmented by percutaneous pedicle screw fixation (PSF) for revision surgery in the lumbar spine and to determine the prognostic factors affecting surgical outcomes. METHODS: The population included 54 consecutively treated patients in whom revision surgery involving ALIF with PSF was performed between 2001 and 2004. There were 22 men and 32 women, whose mean age was 59.5 years (range 25-78 years). The diagnoses prior to revision ALIF were as follows: degenerative disc disease in 25 patients, instability/spondylolisthesis in 15, recurrent disc herniation in seven, and pseudarthrosis in seven. The mean follow-up period was 24 months (range 12-52 months). The mean visual analog scale score for back and leg pain decreased, respectively, from 7.8 to 2.3 and 8.0 to 2.3 (p < 0.001). The mean Oswestry Disability Index score improved from 70 to 25% (p < 0.001). Radiological evidence of fusion was noted in 52 of 54 patients. The mean preoperative segmental lordosis, whole lumbar lordosis, and sacral tilt were 15.2, 35.5, and 28.3 degrees, respectively; these values were significantly increased to 20.4, 40.7, and 31.4degrees, respectively, after revision surgery (p < 0.001). The increase in sacral tilt was positively correlated with improvement in back pain (p = 0.028) and functional status (p = 0.025). CONCLUSIONS: The results demonstrate that ALIF followed by PSF can be an effective alternative in revision surgery of the lumbosacral spine in selected cases. Not only can solid fusion be achieved, sagittal alignment can also be restored in the majority of patients.