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Epigenetic age biomarkers and risk assessment in adult spinal deformity: a novel association of biological age with frailty and disability

Michael M. Safaee, Varun B. Dwaraka, Justin M. Lee, Marissa Fury, Tavis L. Mendez, Ryan Smith, Jue Lin, Dana L. Smith, John F. Burke, Justin K. Scheer, Hannah Went, and Christopher P. Ames

OBJECTIVE

Surgery for spinal deformity has the potential to improve pain, disability, function, self-image, and mental health. These surgical procedures carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring the methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight onto the molecular basis of frailty and to improve current risk assessment tools.

METHODS

Adult patients who underwent deformity surgery were prospectively enrolled. Preoperative whole blood samples were used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC)–based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both quantitative polymerase chain reaction (telomere to single gene [T/S] ratio) and a methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiologists Physical Status Classification System class, and scores on the Charlson Comorbidity Index, adult spinal deformity frailty index (ASD-FI), Edmonton Frail Scale (EFS), Oswestry Disability Index, and Scoliosis Research Society-22r questionnaire (SRS-22r). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and beta coefficients (β) from linear regression, adjusted for BMI and sex, were calculated.

RESULTS

Eighty-three patients were enrolled with a mean age of 65 years, and 45 were women (54%). All patients underwent posterior fusion with a mean of 11 levels fused and 33 (40%) 3-column osteotomies were performed. Among the epigenetic clocks adjusted for BMI and sex, DunedinPACE showed a significant association with ASD-FI (β = 0.041, p = 0.002), EFS (β = 0.696, p = 0.026), and SRS-22r (β = 0.174, p = 0.013) scores. PC PhenoAge showed associations with ASD-FI (β = 0.029, p = 0.028) and SRS-22r (β = 0.159, p = 0.018) scores. PC GrimAge showed associations with ASD-FI (β = 0.029, p = 0.037) and SRS-22r (β = 0.161, p = 0.025) scores. Patients with postoperative complications were noted to have shorter telomere length (T/S 0.790 vs 0.858, p = 0.049), even when the analysis controlled for BMI and sex (OR = 1.71, 95% CI 1.07–2.87, p = 0.031).

CONCLUSIONS

Epigenetic clocks showed significant associations with markers of frailty and disability, while patients with postoperative complications had shorter telomere length. These data suggest a potential role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.

In Journal of Neurosurgery: Spine Publish Before Print

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Determining the best vertebra for measuring pelvic incidence and spinopelvic parameters in adult spinal deformity patients with transitional anatomy

Fares Ani, Themistocles S. Protopsaltis, Yesha Parekh, Khalid Odeh, Renaud Lafage, Justin S. Smith, Robert K. Eastlack, Lawrence Lenke, Frank Schwab, Gregory M. Mundis Jr., Munish C. Gupta, Eric O. Klineberg, Virginie Lafage, Robert Hart, Douglas Burton, Christopher P. Ames, Christopher I. Shaffrey, and Shay Bess

OBJECTIVE

The aim of this study was to determine if spinal deformity patients with L5 sacralization should have pelvic incidence (PI) and other spinopelvic parameters measured from the L5 or S1 endplate.

METHODS

This study was a multicenter retrospective comparative cohort study comprising a large database of adult spinal deformity (ASD) patients and a database of asymptomatic individuals. Linear regression modeling was used to determine normative T1 pelvic angle (TPA) and PI − lumbar lordosis (LL) mismatch (PI-LL) based on PI and age in a database of asymptomatic subjects. In an ASD database, patients with radiographic evidence of L5 sacralization had the PI, LL, and TPA measured from the superior endplate of S1 and then also from L5. The differences in TPA and PI-LL from normative were calculated in the sacralization cohort relative to L5 and S1 and correlated to the Oswestry Disability Index (ODI). Patients were grouped based on the Scoliosis Research Society (SRS)–Schwab PI-LL modifier (0, +, or ++) using the L5 PI-LL and S1 PI-LL. Baseline ODI and SF-36 Physical Component Summary (PCS) scores were compared across and within groups.

RESULTS

Among 1179 ASD patients, 276 (23.4%) had transitional anatomy, 176 with sacralized L5 (14.9%) and 100 (8.48%) with lumbarization of S1. The 176 patients with sacralized L5 were analyzed. When measured using the L5 superior endplate, pelvic parameters were significantly smaller than those measured relative to S1 (PI: 24.5° ± 11.0° vs 55.7° ± 12.0°, p = 0.001;TPA: 11.2° ± 12.0° vs 20.3° ± 12.5°, p = 0.001; and PI-LL: 0.67° ± 21.1° vs 11.4° ± 20.8°, p = 0.001). When measured from S1, 76 (43%), 45 (25.6%), and 55 (31.3%) patients had SRS-Schwab PI-LL modifiers of 0, +, and ++, respectively, compared with 124 (70.5%), 22 (12.5%), and 30 (17.0%), respectively, when measured from L5. There were significant differences in ODI and PCS scores as the SRS-Schwab grade increased regardless of L5 or S1 measurement. The L5 group had lower PCS functional scores for SRS-Schwab modifiers 0 and ++ relative to same grades in the S1 group. Offset from normative TPA (0.5° ± 11.1° vs 9.6° ± 10.8°, p = 0.001) and PI-LL (4.5° ± 20.4° vs 15.2° ± 19.3°, p = 0.001) were smaller when measuring from L5. Moreover, S1 measurements were more correlated with health status by ODI (TPA offset from normative: S1, R = 0.326 vs L5, R = 0.285; PI-LL offset from normative: S1, R = 0.318 vs L5, R = 0.274).

CONCLUSIONS

Measuring the PI and spinopelvic parameters at L5 in sacralized anatomy results in underestimating spinal deformity and is less correlated with health-related quality of life. Surgeons may consider measuring PI and spinopelvic parameters relative to S1 rather than at L5 in patients with a sacralized L5.

In Journal of Neurosurgery: Spine Publish Before Print

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Economic burden of nonoperative treatment of adult spinal deformity

Peter G. Passias, Waleed Ahmad, Pooja Dave, Renaud Lafage, Virginie Lafage, Jamshaid Mir, Eric O. Klineberg, Khaled M. Kabeish, Jeffrey L. Gum, Breton G. Line, Robert Hart, Douglas Burton, Justin S. Smith, Christopher P. Ames, Christopher I. Shaffrey, Frank Schwab, Richard Hostin, Thomas Buell, D. Kojo Hamilton, and Shay Bess

OBJECTIVE

The purpose of this study was to investigate the cost utility of nonoperative treatment for adult spinal deformity (ASD).

METHODS

Nonoperatively and operatively treated patients who met database criteria for ASD and in whom complete radiographic and health-related quality of life data at baseline and at 2 years were available were included. A cost analysis was completed on the PearlDiver database assessing the average cost of nonoperative treatment prior to surgical intervention based on previously published treatments (NSAIDs, narcotics, muscle relaxants, epidural steroid injections, physical therapy, and chiropractor). Utility data were calculated using the Oswestry Disability Index (ODI) converted to SF-6D with published conversion methods. Quality-adjusted life years (QALYs) used a 3% discount rate to account for residual decline in life expectancy (78.7 years). Minor and major comorbidities and complications were assessed according to the CMS.gov manual’s definitions. Successful nonoperative treatment was defined as a gain in the minimum clinically importance difference (MCID) in both ODI and Scoliosis Research Society (SRS)–pain scores, and failure was defined as a loss in MCID or conversion to operative treatment. Patients with baseline ODI ≤ 20 and continued ODI of ≤ 20 at 2 years were considered nonoperative successful maintenance. The average utilization of nonoperative treatment and cost were applied to the ASD cohort.

RESULTS

A total of 824 patients were included (mean age 58.24 years, 81% female, mean body mass index 27.2 kg/m2). Overall, 75.5% of patients were in the operative and 24.5% were in the nonoperative cohort. At baseline patients in the operative cohort were significantly older, had a greater body mass index, increased pelvic tilt, and increased pelvic incidence–lumbar lordosis mismatch (all p < 0.05). With respect to deformity, patients in the operative group had higher rates of severe (i.e., ++) sagittal deformity according to SRS–Schwab modifiers for pelvic tilt, sagittal vertical axis, and pelvic incidence–lumbar lordosis mismatch (p < 0.05). At 2 years, patients in the operative cohort showed significantly increased rates of a gain in MCID for physical component summary of SF-36, ODI, and SRS-activity, SRS-pain, SRS-appearance, and SRS-mental scores. Cost analysis showed the average cost of nonoperative treatment 2 years prior to surgical intervention to be $2041. Overall, at 2 years patients in the nonoperative cohort had again in ODI of 0.36, did not show a gain in QALYs, and nonoperative treatment was determined to be cost-ineffective. However, a subset of patients in this cohort underwent successful maintenance treatment and had a decrease in ODI of 1.1 and a gain in utility of 0.006 at 2 years. If utility gained for this cohort was sustained to full life expectancy, patients’ cost per QALY was $18,934 compared to a cost per QALY gained of $70,690.79 for posterior-only and $48,273.49 for combined approach in patients in the operative cohort.

CONCLUSIONS

Patients with ASD undergoing operative treatment at baseline had greater sagittal deformity and greater improvement in health-related quality of life postoperatively compared to patients treated nonoperatively. Additionally, patients in the nonoperative cohort overall had an increase in ODI and did not show improvement in utility gained. Patients in the nonoperative cohort who had low disability and sagittal deformity underwent successful maintenance and cost-effective treatment.

In Journal of Neurosurgery: Spine Volume 39: Issue 6 (Dec 2023)

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Predictive role of global spinopelvic alignment and upper instrumented vertebra level in symptomatic proximal junctional kyphosis in adult spinal deformity

Jichao Ye, Sachin Gupta, Ali S. Farooqi, Tsung Yin, Alex Soroceanu, Frank J. Schwab, Virginie Lafage, Michael P. Kelly, Khaled Kebaish, Richard Hostin, Jeffrey L. Gum, Justin S. Smith, Christopher I. Shaffrey, Justin K. Scheer, Themistocles S. Protopsaltis, Peter G. Passias, Eric O. Klineberg, Han Jo Kim, Robert A. Hart, D. Kojo Hamilton, Christopher P. Ames, and Munish C. Gupta

OBJECTIVE

The authors of this study sought to evaluate the predictive role of global sagittal alignment and upper instrumented vertebra (UIV) level in symptomatic proximal junctional kyphosis (PJK) among patients with adult spinal deformity (ASD).

METHODS

Data on ASD patients who had undergone fusion of ≥ 5 vertebrae from 2008 to 2018 and with a minimum follow-up of 1 year were obtained from a prospectively collected multicenter database and evaluated (n = 1312). Radiographs were obtained preoperatively and at 6 weeks, 6 months, 1 year, 2 years, and 3 years postoperatively. The 22-Item Scoliosis Research Society Patient Questionnaire Revised (SRS-22r) scores were collected preoperatively, 1 year postoperatively, and 2 years postoperatively. Symptomatic PJK was defined as a kyphotic increase > 20° in the Cobb angle from the UIV to the UIV+2. At 6 weeks postoperatively, sagittal parameters were evaluated and patients were categorized by global alignment and proportion (GAP) score/category and SRS-Schwab sagittal modifiers. Patients were stratified by UIV level: upper thoracic (UT) UIV ≥ T8 or lower thoracic (LT) UIV ≤ T9.

RESULTS

Patients who developed symptomatic PJK (n = 260) had worse 1-year postoperative SRS-22r mental health (3.70 vs 3.86) and total (3.56 vs 3.67) scores, as well as worse 2-year postoperative self-image (3.45 vs 3.65) and satisfaction (4.03 vs 4.22) scores (all p ≤ 0.04). In the whole study cohort, patients with PJK had less pelvic incidence–lumbar lordosis (PI-LL) mismatch (−0.24° vs 3.29°, p < 0.001) but no difference in their GAP score/category or SRS-Schwab sagittal modifiers compared with the patients without PJK. Regression showed a higher risk of PJK with a pelvic tilt (PT) grade ++ (OR 2.35) and less risk with a PI-LL grade ++ (OR 0.35; both p < 0.01). When specifically analyzing the LT UIV cohort, patients with PJK had a higher GAP score (5.66 vs 4.79), greater PT (23.02° vs 20.90°), and less PI-LL mismatch (1.61° vs 4.45°; all p ≤ 0.02). PJK patients were less likely to be proportioned postoperatively (17.6% vs 30.0%, p = 0.015), and regression demonstrated a greater PJK risk with severe disproportion (OR 1.98) and a PT grade ++ (OR 3.15) but less risk with a PI-LL grade ++ (OR 0.45; all p ≤ 0.01). When specifically evaluating the UT UIV cohort, the PJK patients had less PI-LL mismatch (−2.11° vs 1.45°) but no difference in their GAP score/category. Regression showed a greater PJK risk with a PT grade + (OR 1.58) and a decreased risk with a PI-LL grade ++ (OR 0.21; both p < 0.05).

CONCLUSIONS

Symptomatic PJK leads to worse patient-reported outcomes and is associated with less postoperative PI-LL mismatch and greater postoperative PT. A worse postoperative GAP score and disproportion are only predictive of symptomatic PJK in patients with an LT UIV.

In Journal of Neurosurgery: Spine Volume 39: Issue 6 (Dec 2023)

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Are we improving in the optimization of surgery for high-risk adult cervical spine deformity patients over time?

Presented at the 2023 AANS/CNS Joint Section on Disorders of the Spine and Peripheral Nerves

Peter G. Passias, Peter S. Tretiakov, Justin S. Smith, Renaud Lafage, Bassel Diebo, Justin K. Scheer, Robert K. Eastlack, Alan H. Daniels, Eric O. Klineberg, Khaled M. Khabeish, Gregory M. Mundis Jr., Jay D. Turner, Munish C. Gupta, Han Jo Kim, Frank Schwab, Shay Bess, Virginie Lafage, Christopher P. Ames, and Christopher I. Shaffrey

OBJECTIVE

The aim of this study was to investigate whether surgery for high-risk patients is being optimized over time and if poor outcomes are being minimized.

METHODS

Patients who underwent surgery for cervical deformity (CD) and were ≥ 18 years with baseline and 2-year data were stratified by year of surgery from 2013 to 2018. The cohort was divided into two groups based on when the surgery was performed. Patients in the early cohort underwent surgery between 2013 and 2015 and those in the recent cohort underwent surgery between 2016 and 2018. High-risk patients met at least 2 of the following criteria: 1) baseline C2–7 Cobb angle > 15°, mismatch between T1 slope and cervical lordosis ≥ 35°, C2–7 sagittal vertical axis > 4 cm, or chin-brow vertical angle > 25°; 2) age ≥ 70 years; 3) severe baseline frailty (Miller index); 4) Charlson Comorbidity Index (CCI) ≥ 1 SD above the mean; 5) three-column osteotomy as treatment; and 6) fusion > 10 levels or > 7 levels for elderly patients. The mean comparison analysis assessed differences between groups. Stepwise multivariable linear regression described associations between increasing year of surgery and complications.

RESULTS

Eighty-two CD patients met high-risk criteria (mean age 62.11 ± 10.87 years, 63.7% female, mean BMI 29.70 ± 8.16 kg/m2, and mean CCI 1.07 ± 1.45). The proportion of high-risk patients increased with time, with 41.8% of patients in the early cohort classified as high risk compared with 47.6% of patients in the recent cohort (p > 0.05). Recent high-risk patients were more likely to be female (p = 0.008), have a lower BMI (p = 0.038), and have a higher baseline CCI (p = 0.013). Surgically, high-risk patients in the recent cohort were more likely to undergo low-grade osteotomy (p = 0.003). By postoperative complications, recent high-risk patients were less likely to experience any postoperative adverse events overall (p = 0.020) or complications such as dysphagia (p = 0.045) at 2 years. Regression analysis revealed increasing year of surgery to be correlated with decreasing minor complication rates (p = 0.030), as well as lowered rates of distal junctional kyphosis by 2 years (p = 0.048).

CONCLUSIONS

Over time, high-risk CD patients have an increase in frequency and comorbidity rates but have demonstrated improved postoperative outcomes. These findings suggest that spine surgeons have improved over time in optimizing selection and reducing potential adverse events in high-risk patients.

In Journal of Neurosurgery: Spine Volume 39: Issue 5 (Nov 2023)

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Clinical outcomes and proximal junctional failure in adult spinal deformity patients corrected to normative alignment versus functional alignment

Themistocles S. Protopsaltis, Fares Ani, Alexandra Soroceanu, Renaud Lafage, Han Jo Kim, Eaman Balouch, Zoe Norris, Justin S. Smith, Alan H. Daniels, Eric O. Klineberg, Christopher P. Ames, Robert Hart, Shay Bess, Christopher I. Shaffrey, Frank J. Schwab, Lawrence G. Lenke, Virginie Lafage, and Munish C. Gupta

OBJECTIVE

The objective of this study was to explore the rate of proximal junctional failure (PJF) and functional outcomes of normative alignment goals compared with alignment targets based on age-appropriate physical function.

METHODS

Baseline relationships between age, pelvic incidence (PI), and a component of the T1 pelvic angle (TPA) within the fusion were analyzed in adult spinal deformity (ASD) patients and compared with those of asymptomatic patients. Linear regression modeling was used to determine alignment based on PI and age in asymptomatic patients (normative alignment), and in ASD patients, alignment corresponding to age-appropriate functional status (functional alignment). A cohort of 288 ASD patients was split into two groups based on whether the patient was closer to their normative or functional alignment goal at their 6-week postoperative radiographic follow-up. The rates of proximal junctional kyphosis (PJK) and PJF were determined for each cohort.

RESULTS

In the 288 ASD patients included in this pre- to postoperative analysis, there was no difference in baseline alignment or health-related quality of life (HRQOL) between the normative alignment and functional alignment groups. At 6 weeks, patients with normative alignment had a smaller TPA (4.45° vs 14.1°) and PI minus lumbar lordosis (−7.24° vs 7.4°) (both p < 0.0001) and higher PJK (40% vs 27.2%, p = 0.03) and PJF (17% vs 6.8%, p = 0.008) rates than patients with functional alignment.

CONCLUSIONS

Correction in ASD patients to normative alignment resulted in higher rates of PJK and PJF without improvements in HRQOL. Correction in ASD patients to functional alignment that mirrors the physical function of their age-matched asymptomatic peers is recommended.

In Journal of Neurosurgery: Spine Volume 39: Issue 6 (Dec 2023)

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The impact of baseline cervical malalignment on the development of proximal junctional kyphosis following surgical correction of thoracolumbar adult spinal deformity

Lara Passfall, Bailey Imbo, Virginie Lafage, Renaud Lafage, Justin S. Smith, Breton Line, Andrew J. Schoenfeld, Themistocles Protopsaltis, Alan H. Daniels, Khaled M. Kebaish, Jeffrey L. Gum, Heiko Koller, D. Kojo Hamilton, Richard Hostin, Munish Gupta, Neel Anand, Christopher P. Ames, Robert Hart, Douglas Burton, Frank J. Schwab, Christopher I. Shaffrey, Eric O. Klineberg, Han Jo Kim, Shay Bess, and Peter G. Passias

OBJECTIVE

The objective of this study was to identify the effect of baseline cervical deformity (CD) on proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) in patients with adult spinal deformity (ASD).

METHODS

This study was a retrospective analysis of a prospectively collected, multicenter database comprising ASD patients enrolled at 13 participating centers from 2009 to 2018. Included were ASD patients aged > 18 years with concurrent CD (C2–7 kyphosis < −15°, T1S minus cervical lordosis > 35°, C2–7 sagittal vertical axis > 4 cm, chin-brow vertical angle > 25°, McGregor’s slope > 20°, or C2–T1 kyphosis > 15° across any three vertebrae) who underwent surgery. Patients were grouped according to four deformity classification schemes: Ames and Passias CD modifiers, sagittal morphotypes as described by Kim et al., and the head versus trunk balance system proposed by Mizutani et al. Mean comparison tests and multivariable binary logistic regression analyses were performed to assess the impact of these deformity classifications on PJK and PJF rates up to 3 years following surgery.

RESULTS

A total of 712 patients with concurrent ASD and CD met the inclusion criteria (mean age 61.7 years, 71% female, mean BMI 28.2 kg/m2, and mean Charlson Comorbidity Index 1.90) and underwent surgery (mean number of levels fused 10.1, mean estimated blood loss 1542 mL, and mean operative time 365 minutes; 70% underwent osteotomy). By approach, 59% of the patients underwent a posterior-only approach and 41% underwent a combined approach. Overall, 277 patients (39.1%) had PJK by 1 year postoperatively, and an additional 189 patients (26.7%) developed PJK by 3 years postoperatively. Overall, 65 patients (9.2%) had PJF by 3 years postoperatively. Patients classified as having a cervicothoracic deformity morphotype had higher rates of early PJK than flat neck deformity and cervicothoracic deformity patients (p = 0.020). Compared with the head-balanced patients, trunk-balanced patients had higher rates of PJK and PJF (both p < 0.05). Examining Ames modifier severity showed that patients with moderate and severe deformity by the horizontal gaze modifier had higher rates of PJK (p < 0.001).

CONCLUSIONS

In patients with concurrent cervical and thoracolumbar deformities undergoing isolated thoracolumbar correction, the use of CD classifications allows for preoperative assessment of the potential for PJK and PJF that may aid in determining the correction of extending fusion levels.

In Journal of Neurosurgery: Spine Volume 39: Issue 6 (Dec 2023)

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Use of multiple rods and proximal junctional kyphosis in adult spinal deformity surgery

Jichao Ye, Sachin Gupta, Ali S. Farooqi, Tsung-Cheng Yin, Alex Soroceanu, Frank J. Schwab, Virginie Lafage, Michael P. Kelly, Khaled Kebaish, Richard Hostin, Jeffrey L. Gum, Justin S. Smith, Christopher I. Shaffrey, Justin K. Scheer, Themistocles S. Protopsaltis, Peter G. Passias, Eric O. Klineberg, Han Jo Kim, Robert A. Hart, D. Kojo Hamilton, Christopher P. Ames, and Munish C. Gupta

OBJECTIVE

Multiple rods are utilized in adult spinal deformity (ASD) surgery to increase construct stiffness. However, the impact of multiple rods on proximal junctional kyphosis (PJK) is not well established. This study aimed to investigate the impact of multiple rods on PJK incidence in ASD patients.

METHODS

ASD patients from a prospective multicenter database with a minimum follow-up of 1 year were retrospectively reviewed. Clinical and radiographic data were collected preoperatively, at 6 weeks postoperatively, at 6 months postoperatively, at 1 year postoperatively, and at every subsequent year postoperatively. PJK was defined as a kyphotic increase of > 10° in the Cobb angle from the upper instrumented vertebra (UIV) to UIV+2 as compared with preoperative values. Demographic data, radiographic parameters, and PJK incidence were compared between the multirod and dual-rod patient cohorts. PJK-free survival analysis was performed using Cox regression to control for demographic characteristics, comorbidities, level of fusion, and radiographic parameters.

RESULTS

Overall, 307/1300 (23.62%) cases utilized multiple rods. Cases with multiple rods were more likely to be revisions (68.4% vs 46.5%, p < 0.001), to be posterior only (80.7% vs 61.5%, p < 0.001), involve more levels of fusion (mean 11.73 vs 10.60, p < 0.001), and include 3-column osteotomy (42.9% vs 17.1%, p < 0.001). Patients with multiple rods also had greater preoperative pelvic retroversion (mean pelvic tilt 27.95° vs 23.58°, p < 0.001), greater thoracolumbar junction kyphosis (−15.9° vs −11.9°, p = 0.001), and more severe sagittal malalignment (C7–S1 sagittal vertical axis 99.76 mm vs 62.23 mm, p < 0.001), all of which corrected postoperatively. Patients with multiple rods had similar incidence rates of PJK (58.6% vs 58.1%) and revision surgery (13.0% vs 17.7%). The PJK-free survival analysis demonstrated equivalent PJK-free survival durations among the patients with multiple rods (HR 0.889, 95% CI 0.745–1.062, p = 0.195) after controlling for demographic and radiographic parameters. Further stratification based on implant metal type demonstrated noninferior PJK incidence rates with multiple rods in the titanium (57.1% vs 54.6%, p = 0.858), cobalt chrome (60.5% vs 58.7%, p = 0.646), and stainless steel (20% vs 63.7%, p = 0.008) cohorts.

CONCLUSIONS

Multirod constructs for ASD are most frequently utilized in revision, long-level reconstructions with 3-column osteotomy. The use of multiple rods in ASD surgery does not result in an increased incidence of PJK and is not affected by rod metal type.

In Journal of Neurosurgery: Spine Volume 39: Issue 3 (Sep 2023)

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Calibration of a comprehensive predictive model for the development of proximal junctional kyphosis and failure in adult spinal deformity patients with consideration of contemporary goals and techniques

Peter S. Tretiakov, Renaud Lafage, Justin S. Smith, Breton G. Line, Bassel G. Diebo, Alan H. Daniels, Jeffrey Gum, Themistocles Protopsaltis, D. Kojo Hamilton, Alex Soroceanu, Justin K. Scheer, Robert K. Eastlack, Gregory Mundis Jr., Pierce D. Nunley, Eric O. Klineberg, Khaled Kebaish, Stephen Lewis, Lawrence Lenke, Richard Hostin, Munish C. Gupta, Christopher P. Ames, Robert A. Hart, Douglas Burton, Christopher I. Shaffrey, Frank Schwab, Shay Bess, Han Jo Kim, Virginie Lafage, and Peter G. Passias

OBJECTIVE

The objective of this study was to calibrate an updated predictive model incorporating novel clinical, radiographic, and prophylactic measures to assess the risk of proximal junctional kyphosis (PJK) and failure (PJF).

METHODS

Operative patients with adult spinal deformity (ASD) and baseline and 2-year postoperative data were included. PJK was defined as ≥ 10° in sagittal Cobb angle between the inferior uppermost instrumented vertebra (UIV) endplate and superior endplate of the UIV + 2 vertebrae. PJF was radiographically defined as a proximal junctional sagittal Cobb angle ≥ 15° with the presence of structural failure and/or mechanical instability, or PJK with reoperation. Backstep conditional binary supervised learning models assessed baseline demographic, clinical, and surgical information to predict the occurrence of PJK and PJF. Internal cross validation of the model was performed via a 70%/30% cohort split. Conditional inference tree analysis determined thresholds at an alpha level of 0.05.

RESULTS

Seven hundred seventy-nine patients with ASD (mean 59.87 ± 14.24 years, 78% female, mean BMI 27.78 ± 6.02 kg/m2, mean Charlson Comorbidity Index 1.74 ± 1.71) were included. PJK developed in 50.2% of patients, and 10.5% developed PJF by their last recorded visit. The six most significant demographic, radiographic, surgical, and postoperative predictors of PJK/PJF were baseline age ≥ 74 years, baseline sagittal age-adjusted score (SAAS) T1 pelvic angle modifier > 1, baseline SAAS pelvic tilt modifier > 0, levels fused > 10, nonuse of prophylaxis measures, and 6-week SAAS pelvic incidence minus lumbar lordosis modifier > 1 (all p < 0.015). Overall, the model was deemed significant (p < 0.001), and internally validated receiver operating characteristic analysis returned an area under the curve of 0.923, indicating robust model fit.

CONCLUSIONS

PJK and PJF remain critical concerns in ASD surgery, and efforts to reduce the occurrence of PJK and PJF have resulted in the development of novel prophylactic techniques and enhanced clinical and radiographic selection criteria. This study demonstrates a validated model incorporating such techniques that may allow for the prediction of clinically significant PJK and PJF, and thus assist in optimizing patient selection, enhancing intraoperative decision making, and reducing postoperative complications in ASD surgery.

In Journal of Neurosurgery: Spine Volume 39: Issue 3 (Sep 2023)

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Duration of neurological deficit and outcomes in the surgical treatment of spinal coccidioidomycosis

Alexa Semonche, Justin K. Scheer, Vinil N. Shah, Monica Fung, Lee A. Tan, Dean Chou, Praveen V. Mummaneni, Sigurd H. Berven, Christopher P. Ames, Vedat Deviren, Alekos A. Theologis, and Aaron J. Clark

OBJECTIVE

Vertebral osteomyelitis is a rare complication of coccidioidomycosis infection. Surgical intervention is indicated when there is failure of medical management or presence of neurological deficit, epidural abscess, or spinal instability. The relationship between timing of surgical intervention and recovery of neurological function has not been previously described. The purpose of this study was to investigate if the duration of neurological deficits at presentation affects neurological recovery after surgical intervention.

METHODS

This was a retrospective study of all patients diagnosed with coccidioidomycosis involving the spine at a single tertiary care center between 2012 and 2021. Data collected included patient demographics, clinical presentation, radiographic information, and surgical intervention. The primary outcome was change in neurological examination after surgical intervention, quantified according to the American Spinal Injury Association Impairment Scale. The secondary outcome was the complication rate. Logistic regression was used to test if the duration of neurological deficits was associated with improvement in the neurological examination after surgery.

RESULTS

Twenty-seven patients presented with spinal coccidioidomycosis between 2012 and 2021; 20 of these patients had vertebral involvement on spinal imaging with a median follow-up of 8.7 months (IQR 1.7–71.2 months). Of the 20 patients with vertebral involvement, 12 (60.0%) presented with a neurological deficit with a median duration of 20 days (range 1–61 days). Most patients presenting with neurological deficit (11/12, 91.7%) underwent surgical intervention. Nine (81.2%) of these 11 patients had an improved neurological examination after surgery and the other 2 had stable deficits. Seven patients had improved recovery sufficient to improve by 1 grade according to the AIS. The duration of neurological deficits on presentation was not significantly associated with neurological improvement after surgery (p = 0.49, Fisher’s exact test).

CONCLUSIONS

The duration of neurological deficits on presentation should not deter surgeons from operative intervention in cases of spinal coccidioidomycosis.

In Journal of Neurosurgery: Spine Volume 39: Issue 3 (Sep 2023)