Samuel K. Cho

Proximal junctional kyphosis in adolescent idiopathic scoliosis after 3 different types of posterior segmental spinal instrumentation and fusions: incidence and risk factor analysis of 410 cases.

Study Design. Retrospective study. Objective. Determine proximal junctional kyphosis (PJK) prevalence and analyze risk factors associated with PJK in adolescent idiopathic scoliosis (AIS) patients following 3 different posterior segmental spinal instrumentation and fusion surgeries. Summary of Background Data. No comparison study exists on proximal junctional AIS changes following 3 different segmental posterior spinal instrumentation and fusion surgeries at 2 years postoperative. Methods. A clinical/radiographic assessment was conducted in 410 consecutive AIS patients (average age = 14.7, range = 10.6–20) (men/women = 73/337) treated with instrumented segmental posterior spinal fusion with 2-year follow-up. Revision and anterior cases were not included. Standing long-cassette radiographic measurements were analyzed including various sagittal/coronal parameters for preoperative, early postoperative, and 2-year follow-up. Abnormal PJK was defined by proximal junction sagittal Cobb angles between the lower endplate of the uppermost instrumented vertebra and the upper endplate of 2 supradjacent vertebrae ≥+10° and at least 10° greater than the preoperative measurement at 2 years postoperative. Results. PJK prevalence defined at 2 years postoperative was 27% (111 of 410 patients). Statistically significant factors: larger preoperative thoracic kyphosis angle (T5–T12 >40° vs. T5–T12 10°–40° vs. T5–T12 <10°; P < 0.0001), greater immediate postoperative thoracic kyphosis angle decrease (decrease >5° vs. 5° decrease-5° increase vs. increase >5°; P < 0.0001), thoracoplasty versus no thoracoplasty (P = 0.001), and men versus women (P = 0.007). Instrumentation types (hook-only vs. proximal hook, distal pedicle screw vs. pedicle screw P = 0.058), number of fused vertebrae >12 versus 12≥ (P = 0.12), the uppermost instrumented vertebra among T2, T3, T4, T5 (P = 0.75). There were no significant differences in Scoliosis Research Society Patient Questionnaire-24 outcome-scores (PJK total score = 97.0, self-image subscales = 21.3 vs. non-PJK group = 95.3, 21.0) (P = 0.34 total score, P = 0.54 self-image subscale). Conclusion. Two-year postoperative PJK prevalence in AIS following 3 different posterior segmental spinal instrumentation and fusion surgeries was 27%. A larger preoperative thoracic kyphosis angle, greater immediate postoperative thoracic kyphosis angle decrease, thoracoplasty, and male sex correlated significantly with PJK. There were no significant differences in Scoliosis Research Society Patient Questionnaire-24 outcome-scores between the PJK and non-PJK group.

Major complications in revision adult deformity surgery: Risk factors and clinical outcomes with 2- to 7-year follow-up

Study Design. Retrospective cohort comparative study. Objective. To determine the prevalence of major complications, identify risk factors, and assess long-term clinical benefit after revision adult spinal deformity surgery. Summary of Background Data. No study has analyzed risk factors for major complications in long revision fusion surgery and whether or not occurrence of a major complication affects ultimate clinical outcome. Methods. Analysis of consecutive adult patients who underwent multilevel revision surgery for spinal deformity with a minimum 2-year follow-up was performed. All complications were classified as either major or minor. Outcome analysis was conducted with the Scoliosis Research Society and Oswestry Disability Index scores. Results. A total of 166 patients (mean age = 53.8 years) were identified with a mean follow-up of 3.5 years (range: 2–7). Primary diagnoses included idiopathic/de novo scoliosis (107), degenerative (35), trauma (7), neuromuscular scoliosis (6), congenital deformity (5), ankylosing spondylitis (2), tumor (2), Scheuermann kyphosis (1), and rheumatoid arthritis (1). Most common secondary diagnoses that necessitated revision surgery were adjacent segment disease, fixed sagittal imbalance, and pseudarthrosis. Overall, 34.3% of patients developed major complications (19.3% perioperative; 18.7% follow-up). Associated risk factors for perioperative complications were patient- (age > 60 years, medical comorbidities, obesity) and surgery-related (pedicle subtraction osteotomy). Performance of a 3-column osteotomy and postoperative radiographic changes that suggested progressive loss of sagittal correction were recognized as risk factors for follow-up complications. Equivalent outcome scores were reported by patients preoperatively, but those experiencing follow-up complications reported lower scores at the final follow-up. Conclusion. Overall, 34.4% of patients experienced major complications after long revision fusion surgery. Different risk factors were identified for perioperative versus follow-up complications. The occurrence of a follow-up, not but perioperative, major complication seemed to have a negative impact on ultimate clinical outcome.

Methods to decrease postoperative infections following posterior cervical spine surgery.

BACKGROUND To decrease surgical site infections, we initiated a protocol of preliminary preparation of the skin and surrounding plastic drapes with alcohol foam, and the placement of a suprafascial drain in addition to a subfascial drain in obese patients in 2004. In 2008, we additionally placed 500 mg of vancomycin powder into the wound prior to closure. The purpose of this study was to analyze the infection rates for three groups: Group C (control that received standard perioperative intravenous antibiotics alone), Group AD (alcohol foam and drain), and Group VAD (vancomycin with alcohol foam and drain). METHODS A consecutive series of 1001 all-posterior cervical spine surgical procedures performed at one institution by the senior author from 1995 to 2010 was retrospectively reviewed. These surgical procedures included foraminotomy, laminectomy, laminoplasty, arthrodesis, instrumentation, and/or osteotomies. There were 483 patients in Group C, 323 in Group AD, and 195 in Group VAD. RESULTS In Group C, nine (1.86%) of the 483 patients had an acute postoperative deep infection, in which methicillin-resistant Staphylococcus aureus was the most common pathogen. A significantly higher rate of infection was found in patients with an active smoking history (p = 0.008; odds ratio = 2.6 [95% confidence interval, 1.0 to 7.1]), rheumatoid arthritis (p = 0.005; odds ratio = 4.0 [95% confidence interval, 1.4 to 7.9]), and a body mass index of ≥30 kg/m2 (p = 0.005; odds ratio = 4.1 [95% confidence interval, 1.5 to 7.7]). Group AD (n = 323) had one infection, a significant decrease compared with Group C (p = 0.047). In Group VAD, none of the 195 patients had infections, which was also a significant decrease compared with Group C (p = 0.048). CONCLUSIONS In this study, preliminary preparation with alcohol foam and the placement of suprafascial drains for deep wounds resulted in one postoperative deep infection in 323 surgical procedures. The addition of intrawound vancomycin powder in 195 consecutive posterior cervical spine surgical procedures resulted in no infections and no adverse effects. To our knowledge, this is the first description of a technique for significantly decreasing postoperative cervical spine infections.

Comparative analysis of clinical outcome and complications in primary versus revision adult scoliosis surgery

Study Design. A retrospective case comparison study. Objective. We compared clinical outcome and complications in adult patients who underwent primary (P) versus revision (R) scoliosis surgery. Summary of Background Data. There is a paucity of data comparing P versus R adult scoliosis patients with respect to their complication rates and clinical outcome. Methods. Assessment of 250 consecutive adult patients who underwent P versus R surgery for idiopathic or de novo scoliosis between 2002 and 2007, with a minimum 2-year follow-up, was performed. Results. There were 126 patients in the P group and 124 in the R group. Mean age at surgery (P = 51.2 vs. R = 51.6 years, P = 0.79), length of follow-up (P = 3.6 vs. R = 3.6 years, P = 0.94), comorbidities (P = 0.43), and smoking status (P = 0.98) were similar between the 2 groups. Body mass index (P = 25.5 vs. R = 27.4 kg/m2, P = 0.01), number of final instrumented levels (P = 10.5 vs. R 12.1 levels, P = 0.00), fusion to the sacrum (P = 61.0% vs. R = 87.1%, P = 0.00), osteotomy (P = 14.3% vs. R = 54.9%, P = 0.00), length of surgery (P = 6.5 vs. R = 8.2 hours, P = 0.00), and estimated blood loss (P = 1072.1 vs. R = 1401.3 mL, P = 0.05) were different. Primary patients had significantly lower overall complications than revision patients (P = 45.2% vs. R = 58.2%, P = 0.042). Primary patients reported significantly higher preoperative and final clinical outcome measures in function, pain, and subscore SRS domains and ODI compared with revision patients (all P < 0.05). Patients older than 60 years of age, however, reported similar SRS and ODI scores between the 2 groups. The extent of surgical benefit patients received, that is, final minus preoperative score, was similar in all categories between the 2 groups. Conclusion. Adult patients undergoing primary scoliosis surgery had significantly lower overall complications compared with revision patients. Primary patients reported higher preoperative and final clinical outcome measures than revision patients, although this difference disappeared in older patients. The benefit of surgery was similar between the 2 groups.

Soluble factors from the notochordal-rich intervertebral disc inhibit endothelial cell invasion and vessel formation in the presence and absence of pro-inflammatory cytokines

BACKGROUND Chronic low back pain can be associated with the pathological ingrowth of blood vessels and nerves into intervertebral discs (IVDs). The notochord patterns the IVD during development and is a source of anti-angiogenic soluble factors such as Noggin and Chondroitin sulfate (CS). These factors may form the basis for a new minimally invasive strategy to target angiogenesis in the IVD. OBJECTIVE To examine the anti-angiogenic potential of soluble factors from notochordal cells (NCs) and candidates Noggin and CS under healthy culture conditions and in the presence of pro-inflammatory mediators. DESIGN NC conditioned media (NCCM) was generated from porcine NC-rich nucleus pulposus tissue. To assess the effects of NCCM, CS and Noggin on angiogenesis, cell invasion and tubular formation assays were performed using human umbilical vein endothelial cells (HUVECs) ± tumor necrosis factor alpha (TNFα [10 ng/ml]). vascular endothelial growth factor (VEGF)-A, MMP-7, interleukin-6 (IL-6) and IL-8 mRNA levels were assessed using qRT-PCR. RESULTS NCCM (10 & 100%), CS (10 and 100 μg) and Noggin (10 and 100 ng) significantly decreased cell invasion of HUVECs with and without TNFα. NCCM 10% and Noggin 10 ng inhibited tubular formation with and without TNFα and CS 100 μg inhibited tubules in Basal conditions whereas CS 10 μg inhibited tubules with TNFα. NCCM significantly decreased VEGF-A, MMP-7 and IL-6 mRNA levels in HUVECs with and without TNFα. CS and Noggin had no effects on gene expression. CONCLUSIONS We provide the first evidence that soluble factors from NCs can inhibit angiogenesis by suppressing VEGF signaling. Notochordal-derived ligands are a promising minimally invasive strategy targeting neurovascular ingrowth and pain in the degenerated IVD.

Analysis of sagittal spinal alignment in 181 asymptomatic children.

Study Design: A cross-sectional study. Objectives: To determine the “normal” radiographic parameters of the sagittal profile of the spine in asymptomatic children. Summary of Background Data: There was consensus that cervical kyphosis is pathologic, but we suspected that the cervical kyphosis or loss of cervical lordosis is abnormal in asymptomatic children and adolescents. And we measured the pediatric sagittal profiles including the cervical lordosis for asymptomatic subjects. Materials and Methods: Analysis of 181 children without spinal pathology was performed. Radiographic measurements consisted of the following: cervical lordosis; thoracic kyphosis; thoracolumbar sagittal angle; thoracic apex; lumbar apex; lumbar lordosis; sacral inclination; sacral slope; pelvic tilt; and sagittal vertebral axis. Results: The mean cervical lordosis was −4.8±12.0 degrees (negative=lordotic), sagittal vertebral axis −2.1±2.4 cm, thoracic kyphosis +33.2±9.0 degrees, thoracolumbar sagittal angle 5.6±8.4 degrees, lumbar lordosis −48.8±9.0 degrees, sacral inclination 43.9±7.6 degrees, sacral slope 34.9±6.6 degrees, and pelvic tilt 9.4±6.1 degrees. One hundred nine (60.2%) patients had hypolordotic cervical spine (≥−5 degrees). Cervical kyphosis was present in 80 (44.2%) patients. Conclusions: There is significant variability in sagittal profile of the cervical spine in asymptomatic children. Cervical kyphosis was found in approximately 40% of our study cohort.

Frailty Index Is a Significant Predictor of Complications and Mortality After Surgery for Adult Spinal Deformity

Study Design. Retrospective study of prospectively collected data. Objective. To determine if the modified Frailty Index (mFI) could be used to predict postoperative complications in patients undergoing surgery for adult spinal deformity (ASD). Summary of Background Data. Surgery for patients with ASD is associated with high complication rates and significant concerns present during risk stratification with older patients. The mFI is an evaluation tool to describe the frailness of an individual and how their preoperative status may impact postoperative survival and outcomes. Using a large nationwide database, we assessed the utility of this instrument in patients undergoing surgery for ASD. Methods. The American College of Surgeons National Surgical Quality Improvement Program is a large multicenter clinical registry that prospectively collects preoperative variables, patient demographics, operative factors, and 30-day postoperative morbidity and mortality outcomes from about 400 hospitals nationwide. Current Procedural Terminology codes were used to query the database for adults who underwent fusion for spinal deformity. The previously described mFI was calculated based on the number of positive factors and univariate and multivariate logistic regression analysis were used to analyze the risk factors associated with mortality. Results. Overall, 1001 patients were identified and the mean mFI score was 0.09 (range: 0–0.545). Increasing mFI score was associated with higher complication, reoperation, and mortality rates (P < 0.05). mFI of 0.09 and 0.18 was an independent predictor of any complication, mortality, requiring a blood transfusion, pulmonary embolism/deep vein thrombosis, and reoperation (all P < 0.05). In comparison with age >60 years obesity class III, mFI was a superior predictor of several postoperative complications and reoperation. Conclusion. Frailty was an independent predictor of postoperative complications, mortality, and reoperation in patients undergoing surgery for ASD. Preoperative assessment of the mFI in this patient population can be utilized to improve current risk models. Level of Evidence: 3

Inflammatory Kinetics and Efficacy of Anti-inflammatory Treatments on Human Nucleus Pulposus Cells.

Study Design. Human nucleus pulposus (NP) cell culture study investigating response to tumor necrosis factor-&agr; (TNF&agr;), effectiveness of clinically available anti-inflammatory drugs, and interactions between proinflammatory cytokines. Objective. To characterize the kinetic response of proinflammatory cytokines released by human NP cells to TNF&agr; stimulation and the effectiveness of multiple anti-inflammatories with 3 substudies: Timecourse, Same-time blocking, Delayed blocking. Summary of Background Data. Chronic inflammation is a key component of painful intervertebral disc degeneration. Improved efficacy of anti-inflammatories requires better understanding of how quickly NP cells produce proinflammatory cytokines and which proinflammatory mediators are most therapeutically advantageous to target. Methods. Degenerated human NP cells (n = 10) were cultured in alginate with or without TNF&agr; (10 ng/mL). Cells were incubated with 1 of 4 anti-inflammatories (anti-IL-6 receptor/atlizumab, IL-1 receptor anatagonist, anti-TNF&agr;/infliximab and sodium pentosan polysulfate/PPS) in 2 blocking-studies designed to determine how intervention timing influences drug efficacy. Cell viability, protein, and gene expression for IL-1&bgr;, IL-6, and IL-8 were assessed. Results. Timecourse: TNF&agr; substantially increased the amount of IL-6, IL-8, and IL-1&bgr;, with IL-1&bgr; and IL-8 reaching equilibrium within ∼72 hours (IL-1&bgr;: 111 ± 40 pg/mL, IL-8: 8478 ± 957 pg/mL), and IL-6 not reaching steady state after 144 hours (1570 ± 435 pg/mL). Anti-TNF&agr; treatment was most effective at reducing the expression of all cytokines measured when added at the same time as TNF&agr; stimulation. Similar trends were observed when drugs were added 72 hours after TNF&agr; stimulation, however, no anti-inflammatories significantly reduced cytokine levels compared with TNF control. Conclusion. IL-1&bgr;, IL-6, and IL-8 were expressed at different rates and magnitudes suggesting different roles for these cytokines in disease. Autocrine signaling of IL-6 or IL-1&bgr; did not contribute to the expression of any proinflammatory cytokines measured in this study. Anti-inflammatory treatments were most effective when applied early in the inflammatory process, when targeting the source of the inflammation. Level of Evidence: N/A

Association Between BMP-2 and Carcinogenicity.

Study Design. Literature review. Objective. To evaluate the association between recombinant human bone morphogenetic protein-2 (rhBMP-2) and malignancy. Summary of Background Data. The use of rhBMP-2 in spine surgery has been the topic of much debate as studies assessing the association between rhBMP-2 and malignancy have come to conflicting conclusions. Methods. A systematic review of the literature was performed using the PubMed-National Library of Medicine/National Institute of Health databases. Only non-clinical studies directly addressing BMP-2 and cancer were included. Articles were categorized by study type (animal, in vitro cell line/human/animal), primary malignancy, cancer attributes, and whether BMP-2 was pro-malignancy or not. Results. A total of 4,131 articles were reviewed. Of those, 515 articles made reference to both BMP-2 and cancer, 99 of which were found to directly examine the role of BMP-2 in cancer. Seventy-five studies were in vitro and 24 were animal studies. Forty-three studies concluded that BMP-2 enhanced cancer function, whereas 18 studies found that BMP-2 suppressed malignancy. Thirty-six studies did not examine whether BMP-2 enhanced or suppressed cancer function. Fifteen studies demonstrated BMP-2 dose dependence (9 enhancement, 6 suppression) and one study demonstrated no dose dependence. Nine studies demonstrated BMP-2 time dependence (6 enhancement, 3 suppression). However, no study demonstrated that BMP-2 caused cancer de novo. Conclusion. Currently, conflicting data exist with regard to the effect of exogenous BMP-2 on cancer. The majority of studies addressed the role of BMP-2 in prostate (17%), breast (17%), and lung (15%) cancers. Most were in vitro studies (75%) and examined cancer invasiveness and metastatic potential (37%). Of 99 studies, there was no demonstration of BMP-2 causing cancer de novo. However, 43% of studies suggested that BMP-2 enhances tumor function, motivating more definitive research on the topic that also includes clinically meaningful dose- and time-dependence. Level of Evidence: 2

The Top 100 Classic Papers in Lumbar Spine Surgery

Study Design. Bibliometric review of the literature. Objective. To analyze and quantify the most frequently cited papers in lumbar spine surgery and to measure their impact on the entire lumbar spine literature. Summary of Background Data. Lumbar spine surgery is a dynamic and complex field. Basic science and clinical research remain paramount in understanding and advancing the field. While new literature is published at increasing rates, few studies make long-lasting impacts. Methods. The Thomson Reuters Web of Knowledge was searched for citations of all papers relevant to lumbar spine surgery. The number of citations, authorship, year of publication, journal of publication, country of publication, and institution were recorded for each paper. Results. The most cited paper was found to be the classic paper from 1990 by Boden et al that described magnetic resonance imaging findings in individuals without back pain, sciatica, and neurogenic claudication showing that spinal stenosis and herniated discs can be incidentally found when scanning patients. The second most cited study similarly showed that asymptomatic patients who underwent lumbar spine magnetic resonance imaging frequently had lumbar pathology. The third most cited paper was the 2000 publication of Fairbank and Pynsent reviewing the Oswestry Disability Index, the outcome-measure questionnaire most commonly used to evaluate low back pain. The majority of the papers originate in the United States (n = 58), and most were published in Spine (n = 63). Most papers were published in the 1990s (n = 49), and the 3 most common topics were low back pain, biomechanics, and disc degeneration. Conclusion. This report identifies the top 100 papers in lumbar spine surgery and acknowledges those individuals who have contributed the most to the advancement of the study of the lumbar spine and the body of knowledge used to guide evidence-based clinical decision making in lumbar spine surgery today. Level of Evidence: 3