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IntroductionRegression analysis of adult spinal deformity (ASD) databases in North America (NA) has yielded radiographic disability thresholds for sagittal vertical axis (SVA), pelvic tilt (PT), an...

IntroductionAdults with spinal deformity typically present with pain and disability.AimOur objective was to compare outcomes for operative (op) and nonoperative (nonop) treatment for ASD based on a...

IntroductionA high prevalence of residual cervical deformity (CD) has been identified following surgical treatment of adult spinal deformity (ASD). Development of the new onset CD is less understood and its clinical impact unclear. This study quantifies the incidence of new onset CD after ASD surgery, identifies predictors of development, and determines the impact outcomes.Materials and MethodsRetrospective review of a prospective multicenter database yielded 215 patients (pts) with complete 2-year follow-up and full length X-rays including the cervical spine. CD was defined by T1S–CL > 20 degrees, C2C7 SVA > 40 mm, or C2C7 kyphosis > 10 degrees. Univariate analysis was performed using t tests or tests of proportion. Multivariate logistic regression was used to determine independent predictors of new CD. The impact of CD on health-related quality of life (HRQL) and satisfaction was measured using repeated measures mixed models or logistic regression as appropriate, accounting for potential confounders.Res...

IntroductionPatients with thoracolumbar deformity employ compensatory mechanisms to maintain horizontal gaze, which may result in cervical malalignment. However, the effects of these reciprocal cha...

Object Three-column resection osteotomies (3COs) are commonly performed for sagittal deformity but have high rates of reported complications. Authors of this study aimed to examine the incidence of and intercenter variability in major intraoperative complications (IOCs), major postoperative complications (POCs) up to 6 weeks postsurgery, and overall complications (that is, both IOCs and POCs). They also aimed to investigate the incidence of and intercenter variability in blood loss during 3CO procedures. Methods The incidence of IOCs, POCs, and overall complications associated with 3COs were retrospectively determined for the study population and for each of 8 participating surgical centers. The incidence of major blood loss (MBL) over 4 L and the percentage of total blood volume lost were also determined for the study population and each surgical center. Complication rates and blood loss were compared between patients with one and those with two osteotomies, as well as between patients with one thoracic osteotomy (ThO) and those with one lumbar or sacral osteotomy (LSO). Risk factors for developing complications were determined. Results Retrospective review of prospectively acquired data for 423 consecutive patients who had undergone 3CO at 8 surgical centers was performed. The incidence of major IOCs, POCs, and overall complications was 7%, 39%, and 42%, respectively, for the study population overall. The most common IOC was spinal cord deficit (2.6%) and the most common POC was unplanned return to the operating room (19.4%). Patients with two osteotomies had more POCs (56% vs 38%, p = 0.04) than the patients with one osteotomy. Those with ThO had more IOCs (16% vs 6%, p = 0.03), POCs (58% vs 34%, p < 0.01), and overall complications (67% vs 37%, p < 0.01) than the patients with LSO. There was significant variation in the incidence of IOCs, POCs, and overall complications among the 8 sites (p < 0.01). The incidence of MBL was 24% for the study population, which varied significantly between sites (p < 0.01). Patients with MBL had a higher risk of IOCs, POCs, and overall complications (OR 2.15, 1.76, and 2.01, respectively). The average percentage of total blood volume lost was 55% for the study population, which also varied among sites (p < 0.01). Conclusions Given the complexity of 3COs for spinal deformity, it is important for spine surgeons to understand the risk factors and complication rates associated with these procedures. In this study, the overall incidence of major complications following 3CO procedures was 42%. Risks for developing complications included an older age (> 60 years), two osteotomies, ThO, and MBL.

Object The goal in this study was to evaluate the risk factors for complications, including new neurological deficits, in the largest cohort of patients with adult spinal deformity to date. Methods The Scoli-RISK-1 inclusion criteria were used to identify eligible patients from 5 centers who were treated between June 1, 2009, and June 1, 2011. Records were reviewed for patient demographic information, surgical data, and reports of perioperative complications. Neurological deficits were recorded as preexisting or as new deficits. Patients who underwent 3-column osteotomies (3COs) were compared with those who did not (posterior spinal fusion [PSF]). Between-group comparisons were performed using independent samples t-tests and chi-square analyses. Results Two hundred seven patients were identified—75 who underwent PSF and 132 treated with 3CO. In the latter group, patients were older (58.9 vs 49.4 years, p < 0.001), had a higher body mass index (29.0 vs 25.8, p = 0.029), smaller preoperative coronal Cobb measurements (33.8° vs 56.4°, p < 0.001), more preoperative sagittal malalignment (11.7 cm vs 5.4 cm, p < 0.001), and similar sagittal Cobb measurements (45.8° vs 57.7°, p = 0.113). Operating times were similar (393 vs 423 minutes, p = 0.130), although patients in the 3CO group sustained higher estimated blood loss (2120 vs 1700 ml, p = 0.066). Rates of new neurological deficits were similar (PSF: 6.7% vs 3CO: 9.9%, p = 0.389), and rates of any perioperative medical complication were similar (PSF: 46.7% vs 3CO: 50.8%, p = 0.571). Patients who underwent vertebral column resection (VCR) were more likely to sustain medical complications than those treated with pedicle subtraction osteotomy (73.7% vs 46.9%, p = 0.031), although new neurological deficits were similar (15.8% vs 8.8%, p = 0.348). Regression analysis did not reveal significant predictors of neurological injury or complication from collected data. Conclusions Despite higher estimated blood loss, rates of all complications (49.3%) and new neurological deficits (8.7%) did not vary for patients who underwent complex reconstruction, whether or not a 3CO was performed. Patients who underwent VCR sustained more medical complications without an increase in new neurological deficits. Prospective studies of patient factors, provider factors, and refined surgical data are needed to define and optimize risk factors for complication and neurological deficits.

Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P

Activation of the platelet-derived growth factor (PDGF) signaling system has been implicated in the development and malignant progression of diffuse gliomas. Overexpression of PDGF system components, particularly the alpha subtype receptor (PDGFRA), is common in glial tumors, and PDGFRA gene amplification has been reported in glioblastomas. In order to address the incidence of PDGFRA gene amplification in a broad set of diffuse gliomas, we used Southern and fluorescence in situ hybridization (FISH) analyses to examine 167 astrocytic gliomas (20 grade III and 147 grade IV), 41 anaplastic oligodendrogliomas, and 29 anaplastic oligoastrocytomas. PDGFRA gene amplification was identified in 4 anaplastic oligodendrogliomas and in a single case of anaplastic oligoastrocytoma, but in none of the malignant astrocytomas. Each of the 5 tumors with PDGFRA amplification displayed features generally associated with grade IV malignancy in astrocytic tumors. Consequently, our data indicate that this gene alteration is restricted to tumors having oligodendroglial differentiation and highly anaplastic features.

Our understanding of diffuse glioma development and progression has expanded remarkably over the past decade. As the genetic alterations responsible for these tumors are identified, molecular models of glioma pathogenesis are emerging and hold great promise to explain the biologic mechanisms of these neoplasms. Although these models continue to evolve and remain highly simplified, some of the genetic alterations that they encompass appear to be prognostically useful. Among the astrocytic gliomas, age and tumor grade are the most powerful indicators of patient survival, however, a wide range of variability remains, particularly among the low- grade and anaplastic astrocytomas. Recent reports indicate that alterations of the PTEN tumor suppressor gene are independent predictors of overall survival for anaplastic astrocytoma patients, helping to distinguish the cases with behavior resembling their more malignant counterparts, the glioblastomas. Among the oligodendroglial tumors, alterations of the 1p and 19q chromosome arms have emerged as potentially powerful predictors of overall patient survival and in vivo chemotherapeutic response, while alterations of the p16/CDKN2A tumor suppressor gene suggest shorter overall survival. As our molecular models continue to improve, through functional analyses and the identification of additional genetic contributors, we will expand our capacity to more effectively prognose these patients and to design rational therapeutic strategies.

Exon trapping from a bacterial artificial chromosome (BAC 78138) mapping to the 19q13.3 glioma tumor suppressor candidate region yielded two exons that recognized a 3.6-kb transcript on Northern blot. Screening of a human fetal brain cDNA library with these exons identified three novel genes, designated EHD2, EHD3, and EHD4, which are homologous to the recently characterized human EHD1 (testilin/HPAST) and its mouse homolog Ehd1, as well as to homologs in Drosophila (Past1) and Caenorhabditis elegans. Alignment of the predicted peptide sequences revealed striking similarities, with multiple conserved regions that include a nucleotide-binding consensus site at the N-terminus, a bipartite nuclear localization signal, and an eps15 homology (EH) protein-binding domain with an EF-hand motif at the C-terminus. The genes are specifically expressed, with EHD2 highly expressed in heart, EHD3 in brain and heart, and EHD4 in heart and pancreas. EHD2 was confirmed to originate from BAC 78138 at 19q13.3; radiation hybrid mapping localized EHD3 and EHD4 to 2p21 and 15q11.1, respectively; EHD1 has been previously mapped to 11q13. The three EHD1 paralogs therefore represent novel members of a family of human EH domain-containing proteins that may play a role in endocytosis and signaling. Mutation analysis of the five coding exons of EHD2 in gliomas failed to detect any tumor-specific alterations, thus indicating that EHD2 is an unlikely candidate for the 19q tumor suppressor gene.

Allelic loss of 17p13.3 is observed in approximately 40% of medulloblastomas, suggesting the presence of a tumor suppressor gene in this region. Deletion mapping has defined a region of common loss flanking the telomeric marker D17S34, and a recent report delineated a 9-kb homozygous deletion within the D17S34 locus in one such tumor. Using cDNA selection, we have identified a transcript spanning this deletion, designated (HSA)RPH3AL (rabphillin-3A-like), based on its 77% overall amino acid identity with a recently cloned rat gene, (RNO)Rph3al (originally termed Noc2), a gene putatively involved in regulated endocrine exocytosis through its interactions with the cytoskeleton. We determined the exon-intron boundaries of RPH3AL and screened the coding region for mutations by direct sequencing in DNA extracted from 33 tumor samples with allelic loss of 17p13, including 10 medulloblastoma, 14 follicular thyroid cancer (FTC), and 9 ovarian cancer specimens. No mutations were identified. Thus, despite its location in a homozygously deleted 17p13.3 locus, it is unlikely that RPH3AL is a gene involved in the oncogenesis of medulloblastoma, FTC, or ovarian cancer.

p73, a protein having substantial structural and functional similarity to p53, has recently been identified and demonstrated to be a potential tumor suppressor. Its location on human chromosome 1p36.33 implicates p73 as a candidate for neuroblastoma. Like neuroblastoma, oligodendrogliomas also show a high frequency of deletions in chromosome 1p36.3. To determine whether p73 is a potential tumor suppressor gene involved in the development of oligodendrogliomas, we performed mutation analysis of p73 in oligodendrogliomas with chromosome 1 p-arm deletions. We first determined the genomic organization and the intron-exon boundary sequences of the p73 gene by long PCR, vectorette PCR, and Southern hybridization. This gene spans about 65 kb with a large first intron. Primer pairs for the amplification of each of the 13 p73 encoding exons were designed in corresponding introns. The amplicons were then analyzed using the denaturing high-performance liquid chromatography system for mutations in the p73 gene. Twenty oligodendroglioma samples with 1p36.3 deletions were screened, but no mutations were detected except for several polymorphisms. It is thus clear that p73 is not a candidate gene for oligodendroglioma despite its location in the frequently deleted 1p36.3 region.

A 46-year-old African-American male presented to the hospital with a four-month history of progressive headache, left-sided weakness, and double vision. His past medical history was otherwise unremarkable, and he denied any recent history of fever, chills, respiratory symptoms, or systemic illness. He reported a history of intravenous drug use and having snorted cocaine within the past 12 months. On examination he had dysarthric speech, a partial right cranial nerve III palsy, and mild left hemiparesis (arm and leg). The remainder of his neurological examination was unremarkable. MRI of the head revealed a 2-cm ring-enhancing mass in the right pons (Figure 1). The mass had very low signal on T2-weighted images, and there was no evidence of reduced diffusion on diffusion-weighted imaging (DWI) (1.5 Tesla clinical scanner, single-shot echo-planar, diffusion gradient 0 and 1000 s/mm, acquired in three orthogonal directions). The apparent diffusion coefficient (ADC) of the mass ranged from 1.2 10 mm/s to 1.7 10 mm/s. Moderate T2 prolongation was noted in the pons, extending into the bilateral cerebellar hemispheres and superiorly into the right midbrain. The mass was presumed to be neoplastic based on the imaging findings, and workup for a systemic primary neoplasm was initiated. An open biopsy of the pontine mass was obtained through a right frontotemporal craniotomy with zygomatic osteotomy with image guidance. The lesion was extremely firm, and specimens sent for KOH preparation and frozen section demonstrated yeast. Additional specimens were sent for permanent section and culture. Having obtained a diagnosis, the wound was closed, and the patient was returned to the intensive care unit in stable condition. Amphotericin B therapy was initiated. Results of HIV testing, completed in the postoperative period, were positive, and his CD4 count was 10/ll. Permanent section pathology showed chronic inflammation with associated necrosis and fungal organisms (Figure 2). Biopsy culture grew Histoplasma capsulatum and was confirmed using a DNA probe. He was treated with a two-week course of amphotericin B, followed by a 10week course of IV itraconazole. He was then started on lifetime maintenance oral itraconazole. Highly active antiretroviral therapy (HAART) was initiated after four weeks of itraconazole therapy. DWI is an MRI-based technique that measures the random translational mobility of water molecules, also known as Brownian motion. The more the movement of water is restricted in a tissue, the higher the DWI signal intensity and the lower the ADC. DWI has been applied to multiple disease processes, including ring-enhancing intraparenchymal brain masses. Two of the main differential considerations in the setting of a ring-enhancing intraparenchymal brain lesion are abscess and necrotic tumor. Distinguishing these two lesions on conventional imaging is often

Lower back pain and pain involving the area of the posterior iliac spine are extremely common. Degeneration of the sacroiliac joint (SIJ) is one potential cause for lower back pain and pain radiating into the groin or buttocks. Degenerative changes to the lumbar spine and sacroiliac joints are common. A recent study evaluating SIJ abnormalities in a primary low back pain population demonstrated 31.7% of patients demonstrated SI joint abnormalities.4 As is the case for the evaluation and management of isolated lower back pain, the evaluation, management, and role for surgical intervention in SIJ pain is very controversial.Many patients have degenerative changes of the disc, facet joints, and SIJs. A recent systematic review performed to determine the diagnostic accuracy of tests available to clinicians to identify the disc, facet joint, or SIJ as the source of low back pain concluded that tests do exist that change the probability of the disc or SIJ (but not the facet joint) as the source of low back pain.3 It was also concluded that the usefulness of these tests in clinical practice, particularly for guiding treatment selection, remains unclear.3Although there is general agreement that SIJ pathological changes are a potential cause of pain, there is far less agreement about the optimal management of these conditions. A variety of conditions can cause SIJ dysfunction including degenerative and inflammatory arthritis, trauma, prior lumbosacral fusion, hip arthritis, limb length inequality, infections, and neoplasia.8 There is increasing evidence that image intensifier-guided single periarticular injection can correctly localize pain to the SIJ but the optimal management strategy remains controversial. Recent publications have compared surgical versus injection treatments and fusion versus denervation procedures.1,8 A systematic review found improvement regardless of the treatment, with most studies reporting over 40% improvement in pain as measured by VAS or NRS scores.8 It cautioned that one of the studies reported 17.6% of patients experiencing mild/no pain compared with 82.4% experiencing marked/severe pain at 39 months after SIJ fusion procedures.6,8 This systematic review also noted that despite improvements in reported pain, less than half of patients who had work status reported as returning to work.8Because of the functional and socioeconomic consequences of chronic lower back pain, numerous surgical treatments to improve this condition have been attempted by spinal surgeons through the years. Arthrodesis of the SIJ is a surgical procedure with a long history dating to the beginnings of spinal surgery.7 Poor results, high complication rates and the need for additional surgical procedures have generally diminished the enthusiasm for this procedure until recently.6A variety of “minimally invasive” procedures have been recently introduced that have rekindled enthusiasm for the surgical management of SIJ pathology. The technique demonstrated in the “Stabilization of the SIJ with SI-Bone” is one of these new techniques. There has been a recent publication detailing the very short term clinical outcomes with this technique that reported encouraging results.5 In this series of 50 patients, quality of life questionnaires were available for 49 patients preoperatively, 41 patients at 3 months, 40 at 6 months and only 27 at 12 months, complicating the ability to accurately assess true outcomes.Although the focus of this video by Geisler is on the surgical technique, there should have been more information provided on the expected surgical outcomes and potential complications of SIJ fusion.2 The video only gives minimal information on how to appropriately select patients with potential SIJ pathology for surgical intervention. There are insufficient recommendations on the clinical and radiographic follow-up needed for this procedure. A concern with this implant is whether the porous plasma spray coating on the implant actually results in bone growth across the SIJ or only serves as a stabilizer. If true fusion does not result, deterioration in the clinical result could occur over time.This video nicely demonstrates the surgical technique of stabilization of the SIJ with SI-Bone product. There are numerous unanswered questions regarding patient selection for SIJ fusion or stabilization. There are an increasing number of surgical techniques for treating SIJ pathology and it is not clear which method may provide the best outcomes. Without prospective trials with nonconflicted surgeons and standardized selection criteria, the true role for SIJ fusion procedures in the management of chronic lower back pain will remain murky. The consequences of the unsupported enthusiasm for the surgical management of discogenic back pain still negatively impacts the public perception of spinal surgeons. Much more high quality information is needed regarding the surgical management of SIJ pathology before widespread use of this technique should be adopted.

BACKGROUND: The SRS-Schwab classification of adult spinal deformity (ASD) is a validated system that provides a common language for the complex pathology of ASD. Classification reliability has been reported; however, correlation with treatment has not been assessed. OBJECTIVE: To assess the clinical relevance of the SRS-Schwab classification based on correlations with health-related quality of life (HRQOL) measures and the decision to pursue operative vs nonoperative treatment. METHODS: Prospective analysis of consecutive ASD patients (18 years of age and older) collected through a multicenter group. The SRS-Schwab classification includes a curve type descriptor and 3 sagittal spinopelvic modifiers (sagittal vertical axis, pelvic tilt, pelvic incidence/lumbar lordosis mismatch). Differences in demographics, HRQOL (Oswestry Disability Index, SRS-22, Short Form-36), and classification between operative and nonoperative patients were evaluated. RESULTS: A total of 527 patients (mean age, 52.9 years; range, 18.4-85.1 years) met inclusion criteria. Significant differences in HRQOL were identified based on SRS-Schwab curve type, with thoracolumbar and primary sagittal deformities associated with greater disability and poorer health status than thoracic or double curve deformities. Operative patients had significantly poorer grades for each of the sagittal spinopelvic modifiers, and progressively higher grades were associated with significantly poorer HRQOL (P , .05). Patients with worse sagittal spinopelvic modifier grades were significantly more likely to require major osteotomies, iliac fixation, and decompression (P # .009). CONCLUSION: The SRS-Schwab classification provides a validated language to describe and categorize ASD. This study demonstrates that the SRS-Schwab classification reflects severity of disease state based on multiple measures of HRQOL and significantly correlates with the important decision of whether to pursue operative or nonoperative treatment.

Methods: This multi-center, consecut ive ret rospect ive analysis was based on patients undergoing PSO surgery for ASD. The prevalence analysis was identified on cases with 2year follow-up standing X-rays and at least 1 follow-up at 6 months or 1 year. Inclusion cr i te r ia a re Adu l t Sp ina l Deformity patients (ASD) with a lumbar osteotomy and a long or short fusion . Risk factors of developing PJK were investigated on patients with 6-month follow-up and short fusion (T10-L2). Inclusion criteria: ASD, lumbar osteotomy and a short fusion.

Pelvic tilt (PT) >25° • Thoracic kyphosis (TK) >60° • Data collection: Demographic, radiographic, HRQOL ASD SF-36 Physical component score (PCS) Mental component score (MCS) Compared to United States (US) Total population norms • Age generational norms • Disease specific norms • Norm based scoring (NBS) MCID values PCS= 3 NBS points MCS= 3 NBS points Conclusions 1) ASD has a similar health impact to cancer, diabetes, heart and lung disease.

Study Design: Multicenter, prospective, nonconsecutive, surgical case series from the International Spine Study Group. Objectives: To evaluate the extent of clinical improvement after surgery for adult spinal deformity (ASD) based on minimal clinically important difference (MCID) and baseline measures. Summary of Background Data: For ASD, evaluation of surgical treatment success using clinical scores should take into account baseline disability and pain and the improvement defined relative to the MCID. Methods: Inclusion criteria included operative patients (age O18 years) with baseline and 2-year SRS-22 scores. Normative values for the SRSscoreswereincludedandimprovementforpatientswasexpressedinnumberofMCIDs.Atbaseline,patientswereclassifiedbydifferences inactivityandpainscoresfromnormativevaluesinfourgroups:‘‘worst,’’‘‘severe,’’‘‘poor,’’and,‘‘moderate.’’At2yearsaftersurgery,patients wereclassifiedintofourgroupsbasedontheirchangeinSRSscoreasfollows:‘‘noimprovementordeterioration,’’‘‘mediocre,’’‘‘satisfactory,’’ or ‘‘optimal.’’ Distinction among curve types was also performed based on the SRS-Schwab ASD classification. Results: A total of 223 patients (age 5 55 � 15 years) were included. At baseline, for 77% of the patients, the worst scores were in Activity or Pain.Atbaseline,thedistributionwas36%‘‘worst,’’28%‘‘severe,’’19%‘‘poor,’’and17%‘‘moderate.’’Patientswithsagittalmalalignmentonly weremorelikelytobeinthe‘‘worst’’state(54%).Theoveralldistributionofimprovementwasasfollows:24%noimprovementordeterioration, 17%mediocre,25%satisfactory,and33%optimal.Forty-onepercentofbaseline‘‘moderate’’patientsachievednoimprovement.Ofthebaseline ‘‘worst’’ patients, 20% achieved no improvement, and 36% and 19% achieved ‘‘satisfactory’’ and ‘‘optimal’’ improvement, respectively. Conclusion: Overall, 24% of patients did not experience improvement after surgery. Patients with baseline severe disability were more likely to perceive improvement than patients with less disability. Level of Evidence: Level II. 2015 Scoliosis Research Society.

Introduction ASD is associated with the highest subspecialty complication rate pseudoarthrosis accounting for the majority. Not long after its introduction, BMP use in ASD surgery increased in an attempt to reduce pseudoarthrosis rates. However, as BMP use has increased, scrutiny has been paid to previous studies showing low complication rates Methods This study is an analysis of complications following ASD surgery for BMP or no BMP (NOBMP). Data analyzed was from a multicenter, prospective, consecutive dataset. Inclusion criteria: Age >=18 years • ASD surgery (scoliosis >=20 degrees, sagittal vertical axis (SVA) >=5cm, pelvic tilt (PT) >=25 degrees, or thoracic kyphosis (TK)>=60 degrees) •