Making a malleable awl using a Steinmann pin for transnasal medial canthopexy.

PURPOSE: The authors designed a malleable awl using a Steinmann pin for transnasal medial canthopexy. METHODS: A Steinmann pin with a small eye at the end (00-0187-001-69, Zimmer Inc., Warsaw, IN, U.S.A.) was prepared, and its distal part was bent using pliers (01-9726, Walter Lorenz Surgical Inc., Jacksonville, FL, U.S.A.) to make it a semicircle with the diameter of the circle being the intercanthal distance of the patient. RESULTS: Transnasal medial canthopexy was performed for 5 patients with telecanthus. All 5 patients had satisfactory results. CONCLUSIONS: This malleable awl might allow easy, safe, and stable fixation of the tendon, permit a safe approach with minimal bone fenestration, and be cost effective.

Preoperative templating before spinal fusion using a fluoroscopic multiplanar imaging system is as accurate as CT scan and uses substantially less radiation.

BACKGROUND: Many surgeons utilize preoperative multiplanar imaging for surgical planning before fusion surgery using pedicle screw instrumentation. Computed tomographic (CT) scan is often used but limited by non-weight-bearing images and high-ionizing radiation. The purpose of this study was to compare pedicle length and width measurements using a multiplanar fluoroscopic imaging system and CT with gross measurements to validate the accuracy of multiplanar fluoroscopic imaging and compare relative radiation exposure between techniques. METHODS: Thirteen intact cadaveric lumbar spine segments were imaged using multiplanar fluoroscopic imaging and conventional CT scan using a low-dose pediatric protocol. At each level and each imaging modality, the 26 pedicles were measured digitally for width and pedicle screw length in accordance with typical presurgical planning procedures. All images were independently measured by 3 observers. After measurement, the specimens were sectioned using a microsurgical saw to facilitate anatomic measurements using calipers. Measurements of the multiplanar fluoroscopic imaging and CT were compared with direct anatomic measurements to quantitate and compare measurement accuracy of CT and fluoroscopic imaging. At the time of image acquisition, radiation exposure from each modality was quantified to allow for comparison of radiation exposures. RESULTS: CT and multiplanar fluoroscopy had similar agreement with gross measurements with respect to pedicle width and length, with κ values for comparison of CT and fluoroscopy with gross measurements falling between 0.61 and 0.73. Both modalities underestimated pedicle width (by 1.9 mm for both modalities) and length (5.5 mm for CT, 6.6 mm for fluoroscopy). Interobserver reliability was higher for fluoroscopy versus CT. High-dose fluoroscopic imaging used 31% of the radiation exposure for CT. CONCLUSIONS: Multiplanar fluoroscopic imaging provides comparable diagnostic preoperative planning to CT scan in an experimental cadaveric model. The use of multiplanar fluoroscopic imaging resulted in between 69% and 85% less radiation exposure than conventional CT scan using pediatric settings. CLINICAL EVIDENCE: This study demonstrates similar results from simulated preoperative templating using fluoroscopic imaging compared with CT scan but with less radiation exposure.

Are the Arbeitsgemeinschaft Für Osteosynthesefragen (AO) Principles for Long Bone Fractures Applicable to 3-Column Osteotomy to Reduce Rod Fracture Rates?

OBJECTIVE: The aim was to determine whether applying Arbeitsgemeinschaft für Osteosynthesefragen (AO) principles for external fixation of long bone fracture to patients with a 3-column osteotomy (3CO) would be associated with reduced rod fracture (RF) rates. SUMMARY OF BACKGROUND DATA: AO dictate principles to follow when fixating long bone fractures: (1) decrease bone-rod distance; (2) increase the number of connecting rods; (3) increase the diameter of rods; (4) increase the working length of screws; (5) use multiaxial fixation. We hypothesized that applying these principles to patients undergoing a 3CO reduces the rate of RF. METHODS: Patients were categorized as having RF versus no rod fracture (non-RF). Details on location and type of instrumentation were collected. Dedicated software was used to calculate the distance between osteotomy site and adjacent pedicle screws, angle between screws and the distance between the osteotomy site and rod. Classic sagittal spinopelvic parameters were evaluated. RESULTS: The study included 170 patients (34=RF, 136=non-RF). There was no difference in age (P=0.224), sagittal vertical axis correction (P=0.287), or lumbar lordosis correction (P=0.36). There was no difference in number of screws cephalad (P=0.62) or caudal (P=0.31) to 3CO site. There was a lower rate of RF for patients with >2 rods versus 2 rods (P<0.001). Patients with multiplanar rod fixation had a lower rod fracture rate (P=0.01). For patients with only 2 rods (N=68), the non-RF cohort had adjacent screws that trended to have less angulation to each other (P=0.06) and adjacent screws that had a larger working length (P=0.03). CONCLUSIONS: A portion of AO principles can be applied to 3CO to reduce RF rates. Placing more rods around a 3CO site, placing rods in multiple planes, and placing adjacent screws with a larger working length around the 3CO site is associated with lower RF rates.

Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia.

Clusterin, also known as apolipoprotein J, is a ubiquitously expressed molecule thought to influence a variety of processes including cell death. In the brain, it accumulates in dying neurons following seizures and hypoxic-ischemic (H-I) injury. Despite this, in vivo evidence that clusterin directly influences cell death is lacking. Following neonatal H-I brain injury in mice (a model of cerebral palsy), there was evidence of apoptotic changes (neuronal caspase-3 activation), as well as accumulation of clusterin in dying neurons. Clusterin-deficient mice had 50% less brain injury following neonatal H-I. Surprisingly, the absence of clusterin had no effect on caspase-3 activation, and clusterin accumulation and caspase-3 activation did not colocalize to the same cells. Studies with cultured cortical neurons demonstrated that exogenous purified astrocyte-secreted clusterin exacerbated oxygen/glucose-deprivation-induced necrotic death. These results indicate that clusterin may be a new therapeutic target to modulate non-caspase-dependent neuronal death following acute brain injury.

Development of a Preoperative Adult Spinal Deformity Comorbidity Score That Correlates With Common Quality and Value Metrics: Length of Stay, Major Complications, and Patient-Reported Outcomes.

STUDY DESIGN: Retrospective review of a multicenter prospective registry. OBJECTIVES: Our goal was to develop a method to risk-stratify adult spinal deformity (ASD) patients on the basis of their accumulated health deficits. We developed a novel comorbidity score (CS) specific to patients with ASD based on their preoperative health state and investigated whether it was associated with major complications, length of hospital stay (LOS), and self-reported outcomes after ASD surgery. METHODS: We identified 273 operatively treated ASD patients with 2-year follow-up. We assessed associations between major complications and age, comorbidities, Charlson Comorbidity Index score, and Oswestry Disability Index score. Significant factors were used to construct the ASD-CS. Associations of ASD-CS with major complications, LOS, and patient-reported outcomes were analyzed. RESULTS: Major complications increased significantly with ASD-CS (P < .01). Compared with patients with ASD-CS of 0, the odds of major complications were 2.8-fold higher (P = .068) in patients with ASD-CS of 1 through 3; 4.5-fold higher (P < .01) in patients with ASD-CS of 4 through 6; and 7.5-fold higher (P < .01) in patients with ASD-CS of 7 or 8. Patients with ASD-CS of 7 or 8 had the longest mean LOS (10.7 days) and worst mean Scoliosis Research Society-22r total score at baseline; however, they experienced the greatest mean improvement (0.98 points) over 2 years. CONCLUSIONS: The ASD-CS is significantly associated with major complications, LOS, and patient-reported outcomes in operatively treated ASD patients.

Deformity correction in thoracic adolescent idiopathic scoliosis.

AIMS: To compare the rates of sagittal and coronal correction for all-pedicle screw instrumentation and hybrid instrumentation using sublaminar bands in the treatment of thoracic adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively reviewed the medical records of 124 patients who had undergone surgery in two centres for the correction of Lenke 1 or 2 AIS. Radiological evaluation was carried out preoperatively, in the early postoperative phase, and at two-year follow-up. Parameters measured included coronal Cobb angles and thoracic kyphosis. Postoperative alignment was compared after matching the cohorts by preoperative coronal Cobb angle, thoracic kyphosis, lumbar lordosis, and pelvic incidence. RESULTS: A total of 179 patients were available for analysis. After matching, 124 patients remained (62 in each cohort). Restoration of thoracic kyphosis was significantly better in the sublaminar band group than in the pedicle screw group (from 23.7° to 27.5° to 34.0° versus 23.9° to 18.7° to 21.5°; all p < 0.001). When the preoperative thoracic kyphosis was less than 20°, sublaminar bands achieved a normal postoperative thoracic kyphosis, whereas pedicle screws did not. In the coronal plane, pedicle screws resulted in a significantly better correction than sublaminar bands at final follow-up (73.0% versus 59.7%; p < 0.001). CONCLUSION: This is the first study to compare sublaminar bands and pedicle screws for the correction of a thoracic AIS. We have shown that pedicle screws give a good coronal correction which is maintained at two-year follow-up. Conversely, sublaminar bands restore the thoracic kyphosis better while pedicle screws are associated with a flattening of the thoracic spine. In patients with preoperative hypokyphosis, sublaminar bands should be used to restore a proper sagittal profile. Cite this article: Bone Joint J 2020;102-B(3):376-382.

Urinary N-Telopeptide Can Predict Pseudarthrosis After Anterior Cervical Decompression and Fusion: A Prospective Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: To examine preoperative urinary cross-linked n-telopeptide (uNTx) and assess for association with fusion rates in patients undergoing single and multi-level anterior cervical decompression and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Although high rates of fusion have been reported for ACDF, the risk of pseudarthrosis remains substantial. An established marker of bone turnover, uNTx may prove useful as a predictor of fusion. METHODS: Patients undergoing primary ACDF with allograft/plating technique from 2015 to 2017 by a single surgeon were consecutively enrolled and preoperative uNTx was collected. Patients undergoing revision, with creatinine >1.2, and with improperly-collected uNTx were excluded. Demographics, laboratory values, and fusion status were assessed at 6 months, 1 year, and 2 years postoperatively. RESULTS: Of the 97 patients enrolled, 69 met inclusion criteria. Of included cases, 41%, 33%, 18%, and 8% underwent 1-, 2-, 3-, and 4-level ACDF, respectively. Overall, fusion rates were 37.3%, 70.9%, and 95.3% at 6 months, 1 year, and 2 years, respectively. uNTx was higher in the fusion group (31.1 vs. 22.2, P = 0.001) at 6 months and 1 year (30.0 vs. 21.0, P = 0.006), with no difference at 2 years. No differences were identified in the proportion of smokers, immunomodulatory agents, corpectomies, or fusion levels between groups. Multivariate regression analysis demonstrated that uNTx is an independent predictor of fusion (odds ratio, OR, 1.124, P = 0.003). Both groups experienced improvements in NDI and VAS neck pain at 6 months with no significant differences noted between groups. Of 16 patients with pseudarthrosis at 1 year, 2 underwent posterior cervical fusion for symptoms. CONCLUSION: Preoperative uNTx was greater in patients with successful ACDF fusion compared with patients with pseudarthrosis at 6 months and 1 year. A negative correlation was found between preoperative uNTx and motion on dynamic imaging. These results suggest that uNTx could serve to identify patients at risk for pseudarthrosis after ACDF. LEVEL OF EVIDENCE: 3.

Reciprocal Changes in Cervical Alignment After Thoracolumbar Arthrodesis for Adult Spinal Deformity.

STUDY DESIGN: Multicenter database review of consecutive adult spinal deformity (ASD) patients. OBJECTIVE: The aim of this study was to identify associations between changes in spinopelvic parameters and cervical alignment after thoracolumbar arthrodesis for ASD. SUMMARY OF BACKGROUND DATA: Reciprocal cervical changes occur after instrumented thoracic spinal arthrodesis. The timing and relationship of these changes to sagittal alignment and upper instrumented vertebra (UIV) selection are unknown. METHODS: In 171 ASD patients treated with thoracolumbar arthrodesis from 2008 to 2012, we assessed changes from baseline to 6-week, 1-year, and 2-year follow-up in C2-C7 sagittal vertical axis (SVA), T1 slope, and C2-C7 lordosis. We used multivariate models to analyze associations between these parameters and UIV selection (T9 or distal vs. proximal to T9) and changes at each time point in thoracic kyphosis (TK), lumbar lordosis (LL), C7-S1 SVA, pelvic incidence, pelvic tilt, and sacral slope. RESULTS: Two-year changes in C2-C7 SVA and T1 slope were significantly associated with baseline to 6-week changes in TK and LL and with UIV selection. Baseline to 2-year changes in C2-C7 lordosis were associated with baseline to 6-week changes in C7-S1 SVA (P = 0.004). Most changes in C2-C7 SVA occurred during the first 6 weeks postoperatively (mean 6-week change in C2-C7 SVA: 2.7 cm, 95% confidence interval [CI]: 0.7-4.7 cm; mean 2-year change in SVA: 2.3 cm, 95% CI: -0.1 to 4.6 cm). At 2 years, on average, there was decrease in C2-C7 lordosis, most of which occurred during the first 6 weeks postoperatively (mean 6-week change: -3.2°, 95% CI: -4.8° to -1.2°; mean 2-year change: -1.3°, 95% CI: - 3.2° to 0.5°). CONCLUSION: After thoracolumbar arthrodesis, reciprocal changes in cervical alignment are associated with postoperative changes in TK, LL, and C7-S1 SVA and with UIV selection. The largest changes occur during the first 6 weeks and persist during 2-year follow-up. LEVEL OF EVIDENCE: 3.

Under Correction of Sagittal Deformities Based on Age-adjusted Alignment Thresholds Leads to Worse Health-related Quality of Life Whereas Over Correction Provides No Additional Benefit.

STUDY DESIGN: Retrospective review of prospectively-collected database. OBJECTIVE: This study aims to compare 2-year clinical outcomes of patients who underwent surgical reconstructions based on their achievement to age-adjusted alignment ideals. SUMMARY OF BACKGROUND DATA: Recent research in sagittal plane has proposed age-adjusted alignment thresholds. However, the impact of these thresholds on postoperative health-related quality of life (HRQOL) is yet to be investigated. METHODS: Patients were included if they were more than 18-years old and underwent surgical correction of adult spinal deformity with a complete 2-year follow-up. Patients were stratified into three groups based on achievement of age-adjusted thresholds in pelvic tilt (PT), pelvic incidence minus lumbar lordosis (PI-LL), and sagittal vertical axis (SVA). First group included patients who reached the exact age-adjusted threshold ±â€Š10 years (MATCHED), other two groups included patients who were over corrected (OVER), and under corrected (UNDER). Clinical outcomes including actual value and offset from age-adjusted Oswestry Disability Index, Short-Form-36 (SF-36) -physical component summary, and Scoliosis Research Society-22r (SRS-22r) were compared between groups at 2 years follow-up. RESULTS: A total of 343 patients (mean, 57 yrs and 83% females) were included. Sagittal profile of the population was: PT = 23.6°, SVA = 65.8 mm, and PI-LL = 15.6°. At 2-year follow-up, there was significant improvement in all sagittal modifiers with 25.7%, 24.3%, and 33.1% of the patients matching their age alignment targets in terms of PT, PI-LL, and SVA, respectively. For PT and PI-LL, the three groups (MATCHED, OVER, and UNDER) had comparable values and offsets from age-adjusted patient reported outcome. However, for SVA groups, patients in UNDER had significantly worse HRQOL than the two other groups. Patients in PT, PI-LL, and SVA UNDER groups were significantly younger than the other groups, P < 0.05. CONCLUSION: At 2 years after adult spinal deformity surgical treatment, only 24.3% to 33.1% of the patients reached age-adjusted alignment thresholds. Those under corrected in SVA demonstrated worse clinical outcomes. No significant improvements were found between matched and overcorrected patients, with overcorrection being an established risk for proximal junctional kyphosis. These results further emphasize the need for patient specific operative planning. LEVEL OF EVIDENCE: 3.

Virtual Modeling of Postoperative Alignment After Adult Spinal Deformity Surgery Helps Predict Associations Between Compensatory Spinopelvic Alignment Changes, Overcorrection, and Proximal Junctional Kyphosis.

STUDY DESIGN: Retrospective review of a prospective multicenter database. OBJECTIVE: To develop a method to analyze sagittal alignment, free of the influence of proximal junctional kyphosis (PJK), and then compare PJK to non-PJK patients using this method. SUMMARY OF BACKGROUND DATA: PJK after adult spinal deformity (ASD) surgery remains problematic as it alters sagittal alignment. The present study proposes a novel virtual modeling technique that attempts to eliminate the confounding effects of PJK on postoperative spinal alignment. METHODS: A virtual spinal modeling technique was developed on a retrospective ASD cohort of patients with multilevel spinal fusions to the pelvis with at least 2-year postoperative follow-up. The virtual postoperative alignment (VIRTUAL) was created from the postoperative alignment of the instrumented segments and the preoperative alignment of the unfused segments. VIRTUAL was validated by comparisons to actual 2-year postoperative alignment (REAL) in non-PJK patients. Patients were then divided into two groups: PJK and non-PJK based on the presence/absence of PJK at 2 years postoperatively. PJK and non-PJK patients were compared using VIRTUAL and REAL. RESULTS: A total of 458 patients (78F, mean 57.9 yr) were analyzed. The validation of VIRTUAL versus REAL demonstrated correlation coefficients greater than 0.7 for all measures except sagittal vertical axis (SVA; r = 0.604). At 2 years, REAL alignment in PJK patients demonstrated a smaller pelvic incidence minus lumbar lordosis and a larger thoracic kyphosis than non-PJK patients, but similar SVA, T1 pelvic angle, and pelvic tilt. An analysis of VIRTUAL demonstrated that patients with PJK had a smaller pelvic incidence minus lumbar lordosis, pelvic tilt, SVA, and T1 pelvic angle than non-PJK patients (P < 0.05). CONCLUSION: This technique demonstrated strong correlations with actual postoperative alignment. Comparisons between REAL and VIRTUAL alignments revealed that postoperative PJK may develop partially as a compensatory mechanism to the overcorrection of sagittal deformities. Future research will evaluate the appropriate thresholds for deformity correction according to age and ASD severity. LEVEL OF EVIDENCE: 3.

Assessment of Lowest Instrumented Vertebra Tilt on Radiographic Measurements in Lenke "C" Modifier Curves Undergoing Selective Thoracic Fusion in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Multicenter, retrospective cohort study. OBJECTIVES: The purpose of this study is to determine how the amount of residual lowest instrumented vertebra (LIV) tilt correlates with radiographic measurements. SUMMARY OF BACKGROUND DATA: When performing a selective thoracic posterior spinal fusion for adolescent idiopathic scoliosis (AIS), the LIV may be tilted into the lumbar curve or made horizontal. METHODS: This is a multicenter retrospective study of 33 consecutive patients with AIS, Lenke types 1 to 4, lumbar modifier C, and a minimum follow-up of 2 years, who underwent selective thoracic posterior spinal fusions. Measurements obtained from pre- and postoperative radiographs were correlated with postoperative LIV tilt. RESULTS: At final follow-up, less postoperative LIV tilt significantly correlated with less thoracic apical translation (p = .023) when controlling for the position of the LIV relative to the stable vertebra and preoperative thoracic and lumbar curve flexibility. LIV tilt was not significantly associated with thoracic Cobb angle, lumbar Cobb angle, lumbar apical translation, coronal balance, sagittal balance, or the amount of correction obtained compared to their preoperative measurements (p > .05). CONCLUSION: Decreased LIV tilt was significantly associated with decreased thoracic apical translation. LIV tilt did not significantly correlate with coronal balance or any other radiographic measurement. We caution that these findings may only be applicable in C modifier curves and when the correct LIV is chosen. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Defining Spino-Pelvic Alignment Thresholds: Should Operative Goals in Adult Spinal Deformity Surgery Account for Age?

STUDY DESIGN: Retrospective review of prospective, multicenter database. OBJECTIVE: The aim of the study was to determine age-specific spino-pelvic parameters, to extrapolate age-specific Oswestry Disability Index (ODI) values from published Short Form (SF)-36 Physical Component Score (PCS) data, and to propose age-specific realignment thresholds for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: The Scoliosis Research Society-Schwab classification offers a framework for defining alignment in patients with ASD. Although age-specific changes in spinal alignment and patient-reported outcomes have been established in the literature, their relationship in the setting of ASD operative realignment has not been reported. METHODS: ASD patients who received operative or nonoperative treatment were consecutively enrolled. Patients were stratified by age, consistent with published US-normative values (Norms) of the SF-36 PCS (<35, 35-44, 45-54, 55-64, 65-74, >75  y old). At baseline, relationships between between radiographic spino-pelvic parameters (lumbar-pelvic mismatch [PI-LL], pelvic tilt [PT], sagittal vertical axis [SVA], and T1 pelvic angle [TPA]), age, and PCS were established using linear regression analysis; normative PCS values were then used to establish age-specific targets. Correlation analysis with ODI and PCS was used to determine age-specific ideal alignment. RESULTS: Baseline analysis included 773 patients (53.7 y old, 54% operative, 83% female). There was a strong correlation between ODI and PCS (r = 0.814, P < 0.001), allowing for the extrapolation of US-normative ODI by age group. Linear regression analysis (all with r > 0.510, P < 0.001) combined with US-normative PCS values demonstrated that ideal spino-pelvic values increased with age, ranging from PT = 10.9 degrees, PI-LL = -10.5 degrees, and SVA = 4.1 mm for patients under 35 years to PT = 28.5 degrees, PI-LL = 16.7 degrees, and SVA = 78.1 mm for patients over 75 years. Clinically, older patients had greater compensation, more degenerative loss of lordosis, and were more pitched forward. CONCLUSION: This study demonstrated that sagittal spino-pelvic alignment varies with age. Thus, operative realignment targets should account for age, with younger patients requiring more rigorous alignment objectives.

Assessment of Lowest Instrumented Vertebra Tilt on Radiographic Measurements in Lenke "C" Modifier Curves Undergoing Selective Thoracic Fusion in Adolescent Idiopathic Scoliosis.

STUDY DESIGN: Multicenter, retrospective cohort study. OBJECTIVES: The purpose of this study is to determine how the amount of residual lowest instrumented vertebra (LIV) tilt correlates with radiographic measurements. When performing a selective thoracic posterior spinal fusion for adolescent idiopathic scoliosis (AIS), the LIV may be tilted into the lumbar curve or made horizontal. METHODS: This is a multicenter retrospective study of 33 consecutive patients with AIS, Lenke types 1 to 4, lumbar modifier C, and a minimum follow-up of 2 years, who underwent selective thoracic posterior spinal fusions. Measurements obtained from pre- and postoperative radiographs were correlated with postoperative LIV tilt. RESULTS: At final follow-up, less postoperative LIV tilt significantly correlated with less thoracic apical translation (p =.023) when controlling for the position of the LIV relative to the stable vertebra and preoperative thoracic and lumbar curve flexibility. LIV tilt was not significantly associated with thoracic Cobb angle, lumbar Cobb angle, lumbar apical translation, coronal balance, sagittal balance, or the amount of correction obtained compared to their preoperative measurements (p >.05). CONCLUSION: Decreased LIV tilt was significantly associated with decreased thoracic apical translation. LIV tilt did not significantly correlate with coronal balance or any other radiographic measurement. We caution that these findings may only be applicable in C modifier curves and when the correct LIV is chosen. LEVEL OF EVIDENCE: Level III, Therapeutic study.

Baseline Patient-Reported Outcomes Correlate Weakly With Radiographic Parameters: A Multicenter, Prospective NIH Adult Symptomatic Lumbar Scoliosis Study of 286 Patients.

STUDY DESIGN: Prospective, cross-sectional study. OBJECTIVE: The aim of the study was to determine which radiographic parameters drive patient-reported outcomes (PROs) in primary presentation adult symptomatic lumbar scoliosis (ASLS). SUMMARY OF BACKGROUND DATA: Previous literature suggests correlations between PROs and sagittal plane deformity (sagittal vertical axis [SVA], pelvic incidence-lumbar lordosis [PI-LL] mismatch, pelvic tilt [PT]). Prior work included revision and primary adult spinal deformity patients. The present study addresses only primary presentation ASLS. METHODS: Prospective baseline data were analyzed on 286 patients enrolled in an NIH RO1 clinical trial by nine centers from 2010 to 2014. INCLUSION CRITERIA: 40 to 80 years old, lumbar Cobb (LC) 30° or higher and Scoliosis Research Society-23 score 4.0 or less in Pain, Function or Self-Image domains, or Oswestry Disability Index (ODI) 20 or higher. Patients were primary presentation (no prior spinal deformity surgery) and had complete baseline data: standing coronal/sagittal 36" radiographs and PROs (ODI, Scoliosis Research Society-23, Short Form-12). Correlation coefficients were calculated to evaluate relations between radiographic parameters and PROs for the study population and a subset of patients with ODI 40 or higher. Analysis of variance was used to identify differences in PROs for radiographic modifier groups. RESULTS: Mean age was 60.3 years. Mean spinopelvic parameters were: LL = -39.2°; SVA = 3.1 cm; sacral slope = 32.5°; PT = 23.9°; PI-LL mismatch = 16.8°. Only weak correlations (0.2-0.4) were identified between population sacral slope, SVA and SVA modifiers, and SRS function. SVA and SVA modifiers were weakly associated with ODI. Although there were more correlations in subset analysis of high-symptom patients, all were weak. Analysis of variance identified significant differences in ODI reported by SVA modifier groups. CONCLUSION: In primary presentation patients with ASLS and a subset of "high-symptom" patients (ODI ≥ 40), only weak associations between baseline PROs and radiographic parameters were identified. For this patient population, these results suggest regional radiographic parameters (LC, LL, PT, PI-LL mismatch) are not drivers of PROs and cannot be used to extrapolate effect on patient-perceived pathology. LEVEL OF EVIDENCE: 2.

The mitochondrial permeability transition pore and nitric oxide synthase mediate early mitochondrial depolarization in astrocytes during oxygen-glucose deprivation.

Recent studies suggest that the degree of mitochondrial dysfunction in cerebral ischemia may be an important determinant of the final extent of tissue injury. Although loss of mitochondrial membrane potential (psi(m)), one index of mitochondrial dysfunction, has been documented in neurons exposed to ischemic conditions, it is not yet known whether astrocytes, which are relatively resistant to ischemic injury, experience changes in psi(m) under similar conditions. To address this, we exposed cortical astrocytes cultured alone or with neurons to oxygen-glucose deprivation (OGD) and monitored psi(m) using tetramethylrhodamine ethyl ester. Both neurons and astrocytes exhibited profound loss of psi(m) after 45-60 min of OGD. However, although this exposure is lethal to nearly all neurons, it is hours less than that needed to kill astrocytes. Astrocyte psi(m) was rescued during OGD by cyclosporin A, a permeability transition pore blocker, and (G)N-nitro-arginine, a nitric oxide synthase inhibitor. Loss of mitochondrial membrane potential in astrocytes was not accompanied by depolarization of the plasma membrane. Recovery of astrocyte psi(m) after reintroduction of O(2) and glucose occurred over a surprisingly long period (>1 hr), suggesting that OGD caused specific, reversible changes in astrocyte mitochondrial physiology beyond the simple lack of O(2) and glucose. Decreased psi(m) was associated with a cyclosporin A-sensitive loss of cytochrome c but not with activation of caspase-3 or caspase-9. Our data suggest that astrocyte mitochondrial depolarization could be a previously unrecognized event early in ischemia and that strategies that target the mitochondrial component of ischemic injury may benefit astrocytes as well as neurons.

Magnitude of preoperative cervical lordotic compensation and C2-T3 angle are correlated to increased risk of postoperative sagittal spinal pelvic malalignment in adult thoracolumbar deformity patients at 2-year follow-up.

BACKGROUND CONTEXT: Cervical deformity (CD) is prevalent among patients with adult spinal deformity (ASD). The effect of baseline cervical alignment on achieving optimal thoracolumbar alignment in ASD surgery is unclear. PURPOSE: This study assesses the relationship between preoperative (preop) cervical spinal parameters and global alignment after thoracolumbar ASD surgery at 2-year follow-up. STUDY DESIGN/SETTING: This study is a retrospective review of a multicenter, prospective database. PATIENT SAMPLE: Surgical ASD patients with 2-year follow-up and cervical X-rays were included. OUTCOME MEASURES: The outcome measures were radiographic parameters and self-reported health-related quality-of-life measures (Short-Form 36 [SF-36], Oswestry Disability Index [ODI], and Scoliosis Research Society 22 [SRS-22]). METHODS: Surgical ASD patients of 18 years and older with scoliosis greater than or equal to 20° and one of the following radiographic parameters were included: sagittal vertical axis (SVA) greater than or equal to 5 cm, pelvic tilt (PT) greater than or equal to 25°, or thoracic kyphosis (TK) greater than 60°. The SRS-Schwab sagittal modifiers (PT, global alignment, and pelvic incidence and lumbar lordosis [PI-LL]) were assessed at 2-year postoperatively as either normal ("0") or abnormal ("+" or "++"). Patients were classified in the aligned group (AG) or malaligned group (MG) at 2-year follow-up if all three sagittal modifiers were normal or abnormal, respectively. Patients were assessed for CD based on the following criteria: C2-C7 SVA greater than 4 cm, C2-C7 SVA less than 4 cm, cervical kyphosis (CL greater than 0), cervical lordosis (CL less than 0), any deformity (C2-C7 SVA greater than 4 cm or CL greater than 0), and both CD (C2-C7 SVA greater than 4 cm and CL greater than 0). Univariate testing was performed using t or chi-square test, looking at the following preop parameters: CD, C2-C7 SVA, C2-T3 SVA, CL, T1 slope (T1S), T1S-CL, C2-T3 angle, LL, TK, PT, C7-S1 SVA, and PI-LL. RESULTS: One hundred four patients met the initial inclusion criteria with 70 in the AG and 34 in MG. Preoperative, patients in the MG had a higher CL (11.7 vs. 4.9, p=.03), higher C2-T3 angle (13.59 vs 4.9 p=.01), higher PT (p<.0001), higher SVA (p<.0001), and higher PI-LL (p<.0001) compared with the AG. Interestingly, the prevalence of CD at baseline was similar for both groups. There was no statistically significant difference among groups in the amount of improvement more than 2 years on the ODI or the Physical Component Summary of SF-36. CONCLUSIONS: Patients with sagittal spinal malalignment associated with significant cervical compensatory lordosis are at increased risk of realignment failure at 2-year follow-up. Assessment of the degree of cervical compensation may be helpful in preop evaluation to assist in realignment outcome prediction.

Protection of PC12 cells glutathione peroxidase in L-DOPA induced cytotoxicity.

L-DOPA may cause side-effects during the treatment of Parkinson's disease. We investigated the role of glutathione peroxidase (GSHPx) in cellular defense against L-DOPA cytotoxicity. A line of PC12 cells overexpressing GSHPx with plasmid pRc/CMV-GSHPx was established and stable transfectants overexpressing GSHPx were used for this study. GSHPx activity was found to be 1.5-fold higher in GSHPx-transfectants than in mock-controlled transfectants. Transfectants over expressing GSHPx were also significantly more resistant to exposure to either L-DOPA or t-butyl hydroperoxide than mock-transfected cells. Results suggested that L-DOPA may cause neuronal cell death by an oxidative pathway and GSHPx may play an important role in cellular defense against oxidative stress.

Radiation increases the activity of oncolytic adenovirus cancer gene therapy vectors that overexpress the ADP (E3-11.6K) protein.

We have described three potential adenovirus type 5 (Ad5)-based replication-competent cancer gene therapy vectors named KD1, KD3, and VRX-007. All three vectors overexpress an Ad5 protein named Adenovirus Death Protein (ADP, also named E3-11.6 K protein). ADP is required for efficient lysis of Ad5-infected cells and spread of virus from cell to cell, and thus its overexpression increases the oncolytic activity of the vectors. KD1 and KD3 contain mutations in the Ad5 E1A gene that knock out binding of the E1A proteins to cellular p300/CBP and pRB; these mutations allow KD1 and KD3 to grow well in cancer cells but not in normal cells. VRX-007 has wild-type E1A. Here we report that radiation increases the oncolytic activity of KD1, KD3, and VRX-007. This increased activity was observed in cultured cells, and it was not because of radiation-induced replication of the vectors. The combination of radiation plus KD3 suppressed the growth of A549 lung adenocarcinoma xenografts in nude mice more efficiently than radiation alone or KD3 alone. The combination of ADP-overexpressing vectors and radiation may have potential in treating cancer.

Thymoma and myotonic dystrophy: successful treatment with chemotherapy and radiation: case report and review of the literature.

We present the case of a 42-year-old woman with myotonic dystrophy and thymoma. She was treated with combination chemotherapy followed by external beam radiation, and remains in remission 19 months after thymoma was diagnosed. The myotonic dystrophy is unchanged. Only six cases of this nature have been reported in the literature, and this patient is the first to be successfully treated with combined modality therapy.

Microvessel density in advanced head and neck squamous cell carcinoma before and after chemotherapy.

OBJECTIVE: Studies of tumor angiogenesis in head and neck squamous cell carcinoma (HNSCC) in regard to correlation with prognostic significance have yielded inconclusive results. To determine whether the microvessel density (MVD) within the tumor of advanced (Stages III and IV) HNSCC has any impact on tumor response to 2-3 courses of paclitaxel (Taxol) and carboplatin, we prospectively studied pre-chemotherapy specimens from patients with previously untreated, advanced stage HNSCC. We also attempted to study residual tumors after chemotherapy to determine if the MVD within the tumor had changed. STUDY DESIGN: The MVD within the tumor was obtained by immunohistochemical staining of the tumors with Q-Bend 10 (CD34). The "hot-spot" areas of each tumor (ie., areas with most intense blood neovascularization) were considered for evaluation. Results were expressed as the Average number of microvessels identified in 5-400x microscope fields (ie., the number of microvessels counted in 5-400x microscope fields divided by 5). SETTING: Tertiary University Medical Center. INTERVENTION: Two to 3 courses of chemotherapy with paclitaxel and carboplatin. MAIN OUTCOME MEASURES: Progression-free and overall survival with 5 years follow-up, RESULTS: The tumoral MVD in 32 HNSCC specimens before chemotherapy ranged from 4.0-39.0 (mean, 14.8; median, 14.2). Eight out of 32 patients achieved pathologically complete remission; their tumoral MVD revealed a mean of 10.9. The 24 remaining patients had pathologically-confirmed residual tumor post-chemotherapy; their tumoral MVD revealed a mean of 16.5. CONCLUSION: Statistical analyses revealed no evidence of a relationship between remission and a MVD > or < 10 or > or < 16.5. There was no correlation of tumoral MVD with overall or progression-free survival. In 15 patients, tumoral MVD results were also available on the post-chemotherapy specimens. The greater the difference of the tumoral MVD between the pre- and post-chemotherapy specimens, the shorter the patients overall and progression-free survival (p = 0.042).