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Operative treatment outcomes for adult cervical deformity: a prospective multicenter assessment with mean 3-year follow-up
Elias, Elias; Bess, Shay; Line, Breton G; Lafage, Virginie; Lafage, Renaud; Klineberg, Eric; Kim, Han Jo; Passias, Peter; Nasser, Zeina; Gum, Jeffrey L; Kebaish, Khaled; Eastlack, Robert; Daniels, Alan H; Mundis, Gregory; Hostin, Richard; Protopsaltis, Themistocles S; Soroceanu, Alex; Hamilton, D Kojo; Kelly, Michael P; Gupta, Munish; Hart, Robert; Schwab, Frank J; Burton, Douglas; Ames, Christopher P; Shaffrey, Christopher I; Smith, Justin S
OBJECTIVE:Adult cervical deformity (ACD) has high complication rates due to surgical complexity and patient frailty. Very few studies have focused on longer-term outcomes of operative ACD treatment. The objective of this study was to assess minimum 2-year outcomes and complications of ACD surgery. METHODS:A multicenter, prospective observational study was performed at 13 centers across the United States to evaluate surgical outcomes for ACD. Demographics, complications, radiographic parameters, and patient-reported outcome measures (PROMs; Neck Disability Index, modified Japanese Orthopaedic Association, EuroQol-5D [EQ-5D], and numeric rating scale [NRS] for neck and back pain) were evaluated, and analyses focused on patients with ≥ 2-year follow-up. RESULTS:Of 169 patients with ACD who were eligible for the study, 102 (60.4%) had a minimum 2-year follow-up (mean 3.4 years, range 2-8.1 years). The mean age at surgery was 62 years (SD 11 years). Surgical approaches included anterior-only (22.8%), posterior-only (39.6%), and combined (37.6%). PROMs significantly improved from baseline to last follow-up, including Neck Disability Index (from 47.3 to 33.0) and modified Japanese Orthopaedic Association score (from 12.0 to 12.8; for patients with baseline score ≤ 14), neck pain NRS (from 6.8 to 3.8), back pain NRS (from 5.5 to 4.8), EQ-5D score (from 0.74 to 0.78), and EQ-5D visual analog scale score (from 59.5 to 66.6) (all p ≤ 0.04). More than half of the patients (n = 58, 56.9%) had at least one complication, with the most common complications including dysphagia, distal junctional kyphosis, instrumentation failure, and cardiopulmonary events. The patients who did not achieve 2-year follow-up (n = 67) were similar to study patients based on baseline demographics, comorbidities, and PROMs. Over the course of follow-up, 23 of the total 169 enrolled patients were reported to have died. Notably, these represent all-cause mortalities during the course of follow-up. CONCLUSIONS:This multicenter, prospective analysis demonstrates that operative treatment for ACD provides significant improvement of health-related quality of life at a mean 3.4-year follow-up, despite high complication rates and a high rate of all-cause mortality that is reflective of the overall frailty of this patient population. To the authors' knowledge, this study represents the largest and most comprehensive prospective effort to date designed to assess the intermediate-term outcomes and complications of operative treatment for ACD.
PMID: 35901674
ISSN: 1547-5646
CID: 5276822
The Clinical Impact of Failing to Achieve Ideal Proportional Realignment in Adult Spinal Deformity Patients
Passias, Peter G; Passfall, Lara; Williamson, Tyler K; Schoenfeld, Andrew J; Owusu-Sarpong, Stephane; Dhillon, Ekamjeet; Krol, Oscar; Kummer, Nicholas A; Tretiakov, Peter; Imbo, Bailey; Joujon-Roche, Rachel; Moattari, Kevin; Lebovic, Jordan; Vira, Shaleen; Diebo, Bassel; Smith, Justin S; Park, Paul; Mummaneni, Praveen; Shabani, Saman; Chou, Dean; Lafage, Renaud; Lafage, Virginie
SUMMARY OF BACKGROUND DATA/BACKGROUND:The impact of not achieving ideal realignment in the global alignment and proportion (GAP) score in adult spinal deformity (ASD) correction on clinical outcomes is understudied at present. OBJECTIVE:To identify the clinical impact of failing to achieve GAP proportionality in ASD surgery. STUDY DESIGN/METHODS:Retrospective cohort. METHODS:Operative ASD patients with fusion to S1/pelvis and with pre-(BL) and 2-year (2Y) data were included. Patients were assessed for matching their 6-week (6W) age-adjusted alignment goals.1 Patients were stratified by age-adjusted match at 6W postoperatively (Matched) and 6W GAP proportionality (proportioned: GAP-P; moderately disproportioned: GAP-MD; severely disproportioned: GAP-SD). Groups were assessed for differences in demographics, surgical factors, radiographic parameters, and complications occurring by 2Y. Multivariable logistic regression was used to assess independent effects of not achieving GAP proportionality on postoperative outcomes for Matched and Unmatched patients. RESULTS:Included: One hundred twenty three ASD patients. At baseline, 39.8% were GAP-SD, and 12.2% GAP-SD at 6W. Of 123 patients, 51.2% (n = 63) had more than or equal to one match at 6W. GAP-SD rates did not differ by being Matched or Unmatched (P = 0.945). GAP-SD/Unmatched patients had higher rates of reoperation, implant failure, and PJF by 2Y postop (all P < 0.05). Regressions controlling for age at BL, levels fused, and CCI, revealed 6W GAP-SD/Unmatched patients had higher odds of reoperation (OR: 54 [3.2-899.9]; P = 0.005), implant failure (OR: 6.9 [1.1-46.1]; P = 0.045), and PJF (OR: 30.1 [1.4-662.6]; P = 0.031). Compared to GAP-P or GAP-MD patients, GAP-SD/Matched patients did not have higher rates of reoperation, implant failure, or junctional failure (all P > 0.05). The regression results for both Matched and Unmatched cohorts were consistent when proportionality was substituted by the continuous GAP score. CONCLUSION/CONCLUSIONS:In ASD patients who meet age-adjusted realignment goals, GAP proportionality does not significantly alter complication rates. However, GAP proportionality remains an important consideration in patients with sub-optimal age-adjusted alignment. In these cases, severe global disproportion is associated with higher rates of reoperation, implant failure, rod fracture, and junctional failure.Level of Evidence: III.
PMID: 35125457
ISSN: 1528-1159
CID: 5156622
Rates of Loosening, Failure, and Revision of Iliac Fixation in Adult Deformity Surgery
Eastlack, Robert K; Soroceanu, Alex; Mundis, Gregory M; Daniels, Alan H; Smith, Justin S; Line, Breton; Passias, Peter; Nunley, Pierce D; Okonkwo, David O; Than, Khoi D; Uribe, Juan; Mummaneni, Praveen V; Chou, Dean; Shaffrey, Christopher I; Bess, Shay
STUDY DESIGN/METHODS:Retrospective cohort review of a prospective multicenter database. OBJECTIVE:Identify rates and variations in lumbopelvic fixation failure after adult spinal deformity (ASD) correction. SUMMARY OF BACKGROUND DATA/BACKGROUND:Traditional iliac (IS) and S2-alar-iliac (S2AI) pelvic fixation methods have unique technical characteristics for their application, and result in varied bio-mechanical and anatomic impact. These differences may lead to variance in lumbopelvic fixation failure types/rates. METHODS:ASD patients undergoing correction with more than five level fusion and pelvic fixation, separated by pelvic fixation type (IS vs. S2AI). Fixation fracture or loosening assessed radiographically (Figure 1). Multivariate logistic regression, accounting for significant confounders, was used to examine differences between the two groups for screw loosening/fracture, rod fracture, and revision surgery. Level of significance set at P< 0.05. RESULTS:Four hundred eighteen of 1422 patients were included (IS = 287, S2AI = 131). The groups had similar age, body mass index (BMI), baseline comorbidities, number of levels fused (P>0.05), baseline health related quality of life measures (HRQLs) (short form survey-36, Oswestry Disability Index [ODI], Scoliosis Research Society [SRS-22], numeric rating scale [NRS] leg and back, P>0.05) and deformity (pelvic tilt [PT], pelvic incidence-lumbar lordosis [PI-LL], and sagittal vertical axis [SVA], P> 0.05). The IS group had more unilateral fixation versus S2AI (12.9% vs. 6%; P = 0.02). The overall lumbopelvic fixation failure rate was 23.74%. Pelvic fixation (13.4%) and S1 screw (2.9%) loosening was more likely with S2AI (odds ratio [OR] 2.63, P = 0.001; OR 6.05, P = 0.022). Pelvic screw (2.3%) and rod fracture (14.1%) rates similar between groups but trended toward less occurrence with S2AI (OR 0.47, P= 0.06). Revision surgery occurred in 22.7%, and in 8.5% for iliac fixation specifically, but with no differences between fixation types (P = 0.55 and P = 0.365). Pelvic fixation failure conferred worse HRQL scores (physical component score [PCS] 36.23 vs. 39.37, P= 0.04; ODI 33.81 vs. 27.93, P = 0.036), and less 2 years improvement (PCS 7.69 vs. 10.46, P = 0.028; SRS 0.83 vs. 1.03, P = 0.019; ODI 12.91 vs. 19.77, P = 0.0016). CONCLUSION/CONCLUSIONS:Lumbopelvic fixation failure rates were high following ASD correction, and associated with lesser clinical improvements. S2AI screws were more likely to demonstrate loosening, but less commonly associated with rod fractures at the lumbopelvic region.
PMID: 35819333
ISSN: 1528-1159
CID: 5269072
Is frailty responsive to surgical correction of adult spinal deformity? An investigation of sagittal re-alignment and frailty component drivers of postoperative frailty status
Passias, Peter G; Segreto, Frank A; Moattari, Kevin A; Lafage, Renaud; Smith, Justin S; Line, Breton G; Eastlack, Robert K; Burton, Douglas C; Hart, Robert A; Bess, Shay; Shaffrey, Christopher I; Ames, Christopher P; Lafage, Virginie
PURPOSE/OBJECTIVE:Frailty has been associated with adverse postoperative outcomes. Recently, a novel frailty index for preoperative risk stratification in patients with adult spinal deformity was developed. Components of the ASD-FI utilize patient comorbidity, clinical symptoms, and patient-reported-outcome-measures (PROMS). Our purpose was to investigate components of the Adult Spinal Deformity Frailty Index (ASD-FI) responsive to surgery and drivers of overall frailty. METHODS:Operative ASD patients ≥ 18 years, undergoing multilevel fusions, with complete baseline, 6 W, 1Y and 2Y ASD-FI scores. Descriptive analysis assessed demographics, radiographic parameters, and surgical details. Pearson bivariate correlations, independent and paired t tests assessed postoperative changes to ASD-FI components, total score, and radiographic parameters. Linear regression models determined the effect of successful surgery (achieving lowest level SRS-Schwab classification modifiers) on change in ASD-FI total scores. RESULTS:409 6-week, 696 1-year, and 253 2-year operative ASD patients were included. 6-week and 1-year baseline frailty scores were 0.34, 2 years was 0.38. Following surgery, 6-week frailty was 0.36 (p = 0.033), 1 year was 0.25 (p < 0.001), and 2 years was 0.28 (p < 0.001). Of the ASD-FI variables, 17/40 improved at 6 weeks, 21/40 at 1 year, and 18/40 at 2 years. Successful surgery significantly predicted decreases in 1-year frailty scores (R = 0.27, p < 0.001), SRS-Schwab SVA modifier was the greatest predictor (Adjusted Beta: - 0.29, p < 0.001). CONCLUSIONS:Improvement in sagittal realignment and functional status correlated with improved postoperative frailty. Additional research and deformity sub-group analyses are needed to describe associations between specific functional activities that correlated with frailty improvement as well as evaluation of modifiable and non-modifiable indices. LEVEL OF EVIDENCE: 3/METHODS/:
PMID: 35262879
ISSN: 2212-1358
CID: 5183562
The Impact of Osteoporosis on Adverse Outcomes After Short Fusion for Degenerative Lumbar Disease
Wolfert, Adam J; Rompala, Alexander; Beyer, George A; Shah, Neil V; Ikwuazom, Chibuokem P; Kim, David; Shah, Sharan T; Passias, Peter G; Lafage, Virginie; Schwab, Frank J; Paulino, Carl B; Diebo, Bassel G
INTRODUCTION/BACKGROUND:Osteoporosis affects nearly 200 million individuals worldwide. There are little available data regarding outcomes in patients with osteoporosis who undergo short-segment lumbar fusion for degenerative disk disease (DDD). We sought to identify a relationship between osteoporosis and risk of adverse outcomes in patients with DDD undergoing short-segment lumbar fusion. METHODS:Using the New York State Statewide Planning and Research Cooperative System, all patients with DDD who underwent 2- to 3-level lumbar fusion from 2009 through 2011 were identified. Patients with bone mineralization disorders and other systemic and endocrine disorders and surgical indications of trauma, systemic disease(s), and infection were excluded. Patients were stratified by the presence or absence of osteoporosis and compared for demographics, hospital-related parameters, and 2-year complications and revision surgeries. Multivariate binary logistic regression models were used to identify notable predictors of complications. RESULTS:A total of 29,028 patients (osteoporosis = 1,353 [4.7%], nonosteoporosis = 27,675 [95.3%]) were included. Patients with osteoporosis were older (66.9 vs 52.6 years), more often female (85.1% vs 48.4%), and White (82.8% vs 73.5%) (all P < 0.001). The Charlson/Deyo comorbidity index did not significantly differ between groups. Hospital lengths of stay and total charges were higher for patients with osteoporosis (4.9 vs 4.1 days; $74,484 vs $73,724; both P < 0.001). Medical complication rates were higher in patients with osteoporosis, including acute renal failure and deep-vein thrombosis (both P < 0.01). This cohort also had higher rates of implant-related (3.4% vs 1.9%) and wound (9.8% vs 5.9%) complications (both P < 0.01). Preoperative osteoporosis was strongly associated with 2-year medical and surgical complications (odds ratios, 1.6 and 1.7) as well as greater odds of revision surgeries (odds ratio, 1.3) (all P < 0.001). CONCLUSION/CONCLUSIONS:Patients with osteoporosis undergoing 2- to 3-level lumbar fusion for DDD were at higher risk of 2-year medical and surgical complications, especially implant-related and wound complications. These findings highlight the importance of rigorous preoperative metabolic workup and patients' optimization before spinal surgery.
PMID: 35297812
ISSN: 1940-5480
CID: 5206582
Radiographic Characteristics of Cervical Deformity (CD) Using a Discriminant Analysis: The Value of Extension Radiographs
Lafage, Renaud; Virk, Sohrab; Elysee, Jonathan; Passias, Peter; Ames, Christopher; Hart, Robert; Shaffrey, Christopher; Mundis, Gregory; Protopsaltis, Themistocles; Gupta, Munish; Klineberg, Eric; Burton, Douglas; Schwab, Frank; Lafage, Virginie
STUDY DESIGN/METHODS:This was a retrospective review of a prospectively collected database. OBJECTIVE:The aim of this study was to delineate radiographic parameters that distinguish severe cervical spine deformity (CSD). SUMMARY OF BACKGROUND DATA/BACKGROUND:Our objective was to define parameters that distinguish severe CSD using a consensus approach combined with discriminant analysis as no system currently exists in the literature. METHODS:Twelve CSD surgeons reviewed preoperative x-rays from a CSD database. A consensus was reached for categorizing patients into a severe cervical deformity (sCD), non-severe cervical deformity (non-sCD), or an indeterminate cohort. Radiographic parameters were found including classic cervical and spinopelvic parameters in neutral/flexion/extension alignment. To perform our discriminant analysis, we selected for parameters that had a significant difference between the sCD and non-sCD groups using the Student t test. A discriminant function analysis was used to determine which variables discriminate between the sCD versus non-sCD. A stepwise analysis was performed to build a model of parameters to delineate sCD. RESULTS:A total of 146 patients with cervical deformity were reviewed (60.5±10.5 y; body mass index: 29.8 kg/m2; 61.3% female). There were 83 (56.8%) classified as sCD and 51 (34.9%) as non-sCD. The comparison analysis led to 16 radiographic parameters that were different between cohorts, and 5 parameters discriminated sCD and non-sCD. These parameters were cervical sagittal vertical axis, T1 slope, maximum focal kyphosis in extension, C2 slope in extension, and number of kyphotic levels in extension. The canonical coefficient of correlation was 0.689, demonstrating a strong association between our model and cervical deformity classification. The accuracy of classification was 87.0%, and cross-validation was 85.2% successful. CONCLUSIONS:More than one third of a series of CSD patients were not considered to have a sCD. Analysis of an initial 17 parameters showed that a subset of 5 parameters can discriminate between sCD versus non-sCD with 85% accuracy. Our study demonstrates that flexion/extension images are critical for defining severe CD.
PMID: 35249971
ISSN: 2380-0194
CID: 5220882
"Reverse roussouly": cervicothoracic curvature ratios define characteristic shapes in adult cervical deformity
Passias, Peter G; Pierce, Katherine E; Williamson, Tyler; Vira, Shaleen; Owusu-Sarpong, Stephane; Singh, Ravinderjit; Krol, Oscar; Passfall, Lara; Kummer, Nicholas; Imbo, Bailey; Joujon-Roche, Rachel; Tretiakov, Peter; Moattari, Kevin; Abola, Matthew V; Ahmad, Waleed; Naessig, Sara; Ahmad, Salman; Singh, Vivek; Diebo, Bassel; Lafage, Virginie
PURPOSE/OBJECTIVE:To investigate normal curvature ratios of the cervicothoracic spine and to establish radiographic thresholds for severe myelopathy and disability, within the context of shape. METHODS:Adult cervical deformity (CD) patients undergoing cervical fusion were included. C2-C7 Cobb angle (CL) and thoracic kyphosis (TK), using T2-T12 Cobb angle, were used as a ratio, ranging from -1 to + 1. Pearson bivariate r and univariate analyses analyzed radiographic correlations and differences in myelopathy(mJOA > 14) or disability(NDI > 40) across ratio groups. RESULTS:Sixty-three CD patients included. Regarding CL:TK ratio, 37 patients had a negative ratio and 26 patients had a positive ratio. A more positive CL:TK correlated with increased TS-CL(r = 0.655, p =  < 0.001)and mJOA(r = 0.530, p = 0.001), but did not correlate with cSVA/SVA or NDI scores. A positive CL:TK ratio was associated with moderate disability(NDI > 40)(OR: 7.97[1.22-52.1], p = 0.030). Regression controlling for CL:TK ratio revealed cSVA > 25 mm increased the odds of moderate to severe myelopathy and cSVA > 30 mm increased the odds of significant neck disability. Lastly, TS-CL > 29 degrees increased the odds of neck disability by 4.1 × with no cutoffs for severe mJOA(p > 0.05). CONCLUSIONS:Cervical deformity patients with an increased CL:TK ratio had higher rates of moderate neck disability at baseline, while patients with a negative ratio had higher rates of moderate myelopathy clinically. Specific thresholds for cSVA and TS-CL predicted severe myelopathy or neck disability scores, regardless of baseline neck shape. A thorough evaluation of the cervical spine should include exploration of relationships with the thoracic spine and may better allow spine surgeons to characterize shapes and curves in cervical deformity patients.
PMID: 35508650
ISSN: 1432-0932
CID: 5216272
Cervical deformity patients with baseline hyperlordosis or hyperkyphosis differ in surgical treatment and radiographic outcomes
Passias, Peter Gust; Alas, Haddy; Kummer, Nicholas; Tretiakov, Peter; Diebo, Bassel G; Lafage, Renaud; Ames, Christopher P; Line, Breton; Klineberg, Eric O; Burton, Douglas C; Uribe, Juan S; Kim, Han Jo; Daniels, Alan H; Bess, Shay; Protopsaltis, Themistocles; Mundis, Gregory M; Shaffrey, Christopher I; Schwab, Frank J; Smith, Justin S; Lafage, Virginie
Background/UNASSIGNED:Patients with symptomatic cervical deformity (CD) requiring surgical correction often present with hyperkyphosis (HK), although patients with hyperlordotic curves may require surgery as well. Few studies have investigated differences in CD corrective surgery with regard to HK and hyperlordosis (HL). Objective/UNASSIGNED:The objective of the study is to evaluate patterns in treatment for CD patients with baseline (BL) HK and HL and understand how extreme curvature of the spine may influence surgical outcomes. Materials and Methods/UNASSIGNED:Operative CD patients with BL and 1-year (1Y) radiographic data were included in the study. Patients were stratified based on BL C2-C7 lordosis (CL) angle: those >1 standard deviation (SD) from the mean (-6.96 ± 21.47°) were hyperlordotic (>14.51°) or hyperkyphotic (<-28.43°) depending on directionality. Patients within 1SD were considered control group. Results/UNASSIGNED:< 0.001), however, postoperative differences in MGS and C0-C2 were not significant. HK drivers of deformity were primarily C (90%), whereas HL had primary CT (38.1%), UT (23.8%), and C (14.3%) drivers. Conclusions/UNASSIGNED:Hyperlodotic patients trended higher revision rates with greater radiographic malalignment at 1-year postoperative, perhaps due to undercorrection compared to kyphotic etiologies.
PMCID:9574121
PMID: 36263336
ISSN: 0974-8237
CID: 5360492
Improved Surgical Correction Relative to Patient-Specific Ideal Spinopelvic Alignment Reduces Pelvic Nonresponse for Severely Malaligned Adult Spinal Deformity Patients
Passias, Peter G; Bortz, Cole; Alas, Haddy; Moattari, Kevin; Brown, Avery; Pierce, Katherine E; Manning, Jordan; Ayres, Ethan W; Varlotta, Christopher; Wang, Erik; Williamson, Tyler K; Imbo, Bailey; Joujon-Roche, Rachel; Tretiakov, Peter; Krol, Oscar; Janjua, Burhan; Sciubba, Daniel; Diebo, Bassel G; Protopsaltis, Themistocles; Buckland, Aaron J; Schwab, Frank J; Lafage, Renaud; Lafage, Virginie
BACKGROUND:Persistent pelvic compensation following adult spinal deformity (ASD) corrective surgery may impair quality of life and result in persistent pathologic lower extremity compensation. Ideal age-specific alignment targets have been proposed to improve surgical outcomes, though it is unclear whether reaching these ideal targets reduces rates of pelvic nonresponse following surgery. Our aim was to assess the relationship between pelvic nonresponse, age-specific alignment, and lower-limb compensation following surgery for ASD. METHODS:Single-center retrospective cohort study. ASD patients were grouped: those who did not improve in Scoliosis Research Society-Schwab pelvic tilt (PT) modifier (pelvic nonresponders [PNR]), and those who improved (pelvic responders [PR]). Groups were propensity score matched for preoperative PT and assessed for differences in spinal and lower extremity alignment. Rates of pelvic nonresponse were compared across patient groups who were undercorrected, overcorrected, or matched age-specific postoperative alignment targets. RESULTS:< 0.05). CONCLUSIONS:For patients with moderate to severe baseline truncal inclination, more aggressive surgical correction relative to ideal age-specific PI-LL was associated with lower rates of pelvic nonresponse. Postoperative alignment targets may need to be adjusted to optimize alignment outcomes for patients with substantial preoperative sagittal deformity. CLINICAL RELEVANCE/CONCLUSIONS:These findings increase our understanding of the poor outcomes that occur despite ideal realignment. Surgical correction of severe global sagittal deformity should be prioritized to mitigate these occurrences. LEVEL OF EVIDENCE: 3/METHODS/:
PMID: 35772972
ISSN: 2211-4599
CID: 5281342
The Inherent Value of Preoperative Optimization-Absolute and Incremental Reduction in Components of Metabolic Syndrome Can Enhance Recovery and Minimize Perioperative Burden
Naessig, Sara; Para, Ashok; Moattari, Kevin; Imbo, Bailey; Williamson, Tyler K; Joujon-Roche, Rachel; Tretiakov, Peter; Passfall, Lara; Krol, Oscar; Kummer, Nicholas; Ahmad, Waleed; Pierce, Katherine; Ayres, Ethan; Vira, Shaleen; Diebo, Bassel; Passias, Peter G
BACKGROUND:Metabolic syndrome (MetS) is an amalgamation of medical disorders that ultimately increase patient complications. Factors such as obesity, hypertension, dyslipidemia, and diabetes are associated with this disease complex. OBJECTIVE:To assess the incremental value of improving MetS in relation to clinical outcomes. STUDY DESIGN/METHODS:Retrospective cohort study. METHODS:tests compared differences in patient demographics. Resolution of metabolic factors was incrementally analyzed for their effect on perioperative complications through utilization of logistic regressions. RESULTS:< 0.001). CONCLUSIONS:Metabolic patients improved in perioperative complications incrementally, demonstrating the utility of efforts to mitigate burden of MetS even if not completely abolished. CLINICAL RELEVANCE/CONCLUSIONS:This review contributes to the assessment of MetS optimization in the field of adult spine surgery. LEVEL OF EVIDENCE: 3/METHODS/:
PMID: 35772985
ISSN: 2211-4599
CID: 5281362