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Study Design: Retrospective analysis of prospectively collected data., Objective: This study evaluates the impact of knee osteoarthritis (OA) and knee arthroplasty on alignments and patient-reported outcomes measures (PROMS) of patients undergoing adult spinal deformity (ASD) corrective surgery., Background: The relationship between knee OA and spinal alignment in patients with ASD is incompletely understood. It is also unknown how patients with knee arthroplasty and ASD compare to ASD patients with native knees., Methods: Baseline full-body radiographs were used, and hip and knee OA were graded by two independent reviewers using the KL classification. Spinopelvic parameters and PROMs were compared across the different knee OA groups and compared between patients with knee replacement and native knees., Results: 199 patients with bilateral non severe OA (G1), 31 patients with unilateral severe knee OA (G2), and 60 patients with bilateral severe knee OA (G3). Patients with severe knee OA presented with worse spinopelvic parameters. However, after multivariable regression analysis controlling for age, frailty, PI, T1PA, knee OA was an independent predictor of knee flexion (G1:-0.02±7.3, G2: 7.8±9.4, G3: 4.5±8.7, P<0.001), and ankle dorsiflexion (G1: 2.3±4.0, G2: 6.6±4.5, G3: 5.1±4.1, P<0.001). There was no difference in PROMs (P>0.05). Secondary analysis included 96 patients: 48 patients (50%) with non-severe knee OA, and 48 patients (50%) with knee replacement. There was no difference in radiographic parameters or PROMs between the groups., Conclusion: In this study of complex ASD patients, patients with worse spinal deformity were more likely to have concomitant knee OA. Knee OA was shown to be a predictor of knee flexion and ankle dorsiflexion angles, but was not associated with worse PROMs in this study population. Patients with knee arthroplasty, however, had comparable spinal alignment and PROMs relative to those with mild OA., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: The spectrum of patients requiring adult spinal deformity (ASD) surgery is highly variable in baseline (BL) risk such as age, frailty, and deformity severity. Although improvements have been realized in ASD surgery over the past decade, it is unknown whether these carry over to high-risk patients. We aim to determine temporal differences in outcomes at 2 years after ASD surgery in patients stratified by BL risk., Methods: Patients ≥18 years with complete pre- (BL) and 2-year (2Y) postoperative data from 2009 to 2018 were categorized as having undergone surgery from 2009 to 2013 [early] or from 2014 to 2018 [late]. High-risk [HR] patients met ≥2 of the criteria: (1) ++ BL pelvic incidence and lumbar lordosis or SVA by Scoliosis Research Society (SRS)-Schwab criteria, (2) elderly [≥70 years], (3) severe BL frailty, (4) high Charlson comorbidity index, (5) undergoing 3-column osteotomy, and (6) fusion of >12 levels, or >7 levels for elderly patients. Demographics, clinical outcomes, radiographic alignment targets, and complication rates were assessed by time period for high-risk patients., Results: Of the 725 patients included, 52% (n = 377) were identified as HR. 47% (n = 338) had surgery pre-2014 [early], and 53% (n = 387) underwent surgery in 2014 or later [late]. There was a higher proportion of HR patients in Late group (56% vs 48%). Analysis by early/late status showed no significant differences in achieving improved radiographic alignment by SRS-Schwab, age-adjusted alignment goals, or global alignment and proportion proportionality by 2Y (all P > .05). Late/HR patients had significantly less poor clinical outcomes per SRS and Oswestry Disability Index (both P < .01). Late/HR patients had fewer complications (63% vs 74%, P = .025), reoperations (17% vs 30%, P = .002), and surgical infections (0.9% vs 4.3%, P = .031). Late/HR patients had lower rates of early proximal junctional kyphosis (10% vs 17%, P = .041) and proximal junctional failure (11% vs 22%, P = .003)., Conclusion: Despite operating on more high-risk patients between 2014 and 2018, surgeons effectively reduced rates of complications, mechanical failures, and reoperations, while simultaneously improving health-related quality of life., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Purpose: To investigate the impact of the Global Alignment and Proportion (GAP) score components on patient outcomes in Adult Spine Deformity (ASD) surgery., Methods: Patients included underwent assessment via the GAP score and its individual components: pelvic version (GAP PV), lumbar lordosis (GAP LL), lumbar distribution index (GAP LDI) and spinopelvic component (GAP SP). Multivariable analyses assessed the association between alignment in these components and clinical outcomes in ASD patients., Results: 762 ASD patients met inclusion criteria. Alignment in GAP SP independently predicted meeting MCID for SR-22S and ODI and was associated with a lower likelihood of developing mechanical complications. Patients aligned in GAP SP were less likely to develop proximal junctional kyphosis (OR 0.42, 0.26-0.73, p = 0.01) and PJF (OR 0.3, 0.13-0.74, p = 0.01). Proportioned alignment in GAP SP with disproportioned alignment in GAP LDI contributed to an increased risk of PJK and PJF (OR 2.67, 95% CI 1.95-6.82, p = 0.045). There was no significant association of GAP SP proportionality and GAP RPV (OR 1.1, 0.86-2.15, p = 0.253) or GAP LL (OR 1.34, 0.78-4.23, p = 0.673) disproportionality with outcomes. Disproportioned alignment in GAP SP but proportioned alignment in both GAP LL and GAP LDI was associated with decreased likelihood of PJK (OR 0.53, 95% CI 0.39-0.94, p = 0.02) and PJF (OR 0.31, 95% CI 0.19-0.67, p = 0.001)., Conclusion: The spinopelvic component of the GAP score is the most significant independent predictor of clinical outcomes. Its interaction with the other components of the GAP score also aids assessment of the risk for mechanical complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Research has focused on the increased correction from a three-column osteotomy (3CO) during adult spinal deformity (ASD) surgery. However, an in-depth analysis on the performance of a 3CO in a cohort of complex spinal deformity cases has not been described., Study Design/setting: This is a retrospective study on a prospectively enrolled, complex ASD database., Purpose: This study aimed to determine if three-column osteotomies demonstrate superior benefit in correction of complex sagittal deformity at the cost of increased perioperative complications., Methods: Surgical complex adult spinal deformity patients were included and grouped into thoracolumbar 3COs compared to those who did not have a 3CO (No 3CO) (remaining cohort). Rigid deformity was defined as ΔLL less than 33% from standing to supine. Severe deformity was defined as global (SVA > 70 mm) or C7-PL > 70 mm, or lumbopelvic (PI-LL > 30°). Means comparison tests assessed correction by 3CO grade/location. Multivariate analysis controlling for baseline deformity evaluated outcomes up to six weeks compared to No 3CO., Results: 648 patients were included (Mean age 61 ± 14.6 years, BMI 27.55 ± 5.8 kg/m 2 , levels fused: 12.6 ± 3.8). 126 underwent 3CO, a 20% higher usage than historical cohorts. 3COs were older, frail, and more likely to undergo revision (OR 5.2, 95% CI [2.6-10.6]; p < .001). 3COs were more likely to present with both severe global/lumbopelvic deformity (OR 4), 62.4% being rigid. 3COs had greater use of secondary rods (OR 4st) and incurred 4 times greater risk for: massive blood loss (> 3500 mL), longer LOS, SICU admission, perioperative wound and spine-related complications, and neurologic complications when performed below L3. 3COs had similar HRQL benefit, but higher perioperative opioid use. Mean segmental correction increased by grade (G3-21; G4-24; G5-27) and was 4 × greater than low-grade osteotomies, especially below L3 (OR 12). 3COs achieved 2 × greater spinopelvic correction. Higher grades properly distributed lordosis 50% of the time except L5. Pelvic compensation and non-response were relieved more often with increasing grade, with greater correction in all lower extremity parameters (p < .01). Due to the increased rate of complications, 3COs trended toward higher perioperative cost ($42,806 vs. $40,046, p = .086)., Conclusion: Three-column osteotomy usage in contemporary complex spinal deformities is generally limited to more disabled individuals undergoing the most severe sagittal and coronal realignment procedures. While there is an increased perioperative cost and prolongation of length of stay with usage, these techniques represent the most powerful realignment techniques available with a dramatic impact on normalization at operative levels and reciprocal changes., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Objective: The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy., Methods: A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying "certain/possible NCSE" was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals., Results: In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (n = 53). The criteria showed a sensitivity of 94% (95% CI: 92-96%), a specificity of 77% (95% CI: 73-81%), a positive predictive value of 34% (95% CI: 30-39%), and a negative predictive value of 99% (95% CI: 98-100%). False positives for "certain NCSE" (n = 16) included many serial seizures and stimulus-induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for "possible NCSE" (n = 79) were mainly represented by different encephalopathies and postictality., Interpretation: The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: Previous work comparing ASD to a normative population demonstrated that a large proportion of lumbar lordosis is lost proximally (L1-L4). The current study expands on these findings by collectively investigating regional angles and spinal contours., Methods: 119 asymptomatic volunteers with full-body free-standing radiographs were used to identify age-and-PI models of each Vertebra Pelvic Angle (VPA) from L5 to T10. These formulas were then applied to a cohort of primary surgical ASD patients without coronal malalignment. Loss of lumbar lordosis (LL) was defined as the offset between age-and-PI normative value and pre-operative alignment. Spine shapes defined by VPAs were compared and analyzed using paired t-tests., Results: 362 ASD patients were identified (age = 64.4 ± 13, 57.1% females). Compared to their age-and-PI normative values, patients demonstrated a significant loss in LL of 17 ± 19° in the following distribution: 14.1% had "No loss" (mean = 0.1 ± 2.3), 22.9% with 10°-loss (mean = 9.9 ± 2.9), 22.1% with 20°-loss (mean = 20.0 ± 2.8), and 29.3% with 30°-loss (mean = 33.8 ± 6.0). "No loss" patients' spine was slightly posterior to the normative shape from L4 to T10 (VPA difference of 2°), while superimposed on the normative one from S1 to L2 and became anterior at L1 in the "10°-loss" group. As LL loss increased, ASD and normative shapes offset extended caudally to L3 for the "20°-loss" group and L4 for the "30°-loss" group., Conclusion: As LL loss increases, the difference between ASD and normative shapes first occurs proximally and then progresses incrementally caudally. Understanding spinal contour and LL loss location may be key to achieving sustainable correction by identifying optimal and personalized postoperative shapes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Summary of Background Data: Yilgor et al developed the lumbar Lordosis Distribution Index to individualize the pelvic mismatch to each patient's pelvic incidence. The cervical lordosis distribution in relation to its apex has not been characterized., Objective: Tailor correction of cervical deformity by incorporating the cervical apex into a distribution index(CLDI) to maximize clinical outcomes while lowering rates of junctional failure., Study Design/setting: Retrospective cohort., Methods: CD patients with complete 2Y data were included. Optimal outcome is defined by no DJF, and meeting Virk et al Good Clinical Outcome Criteria:[Meeting 2 of 3: 1)an NDI<20 or meeting MCID, 2)mJOA>=14, 3)an NRS-Neck<=5 or improved by 2 or more points]. C2-T2 lordosis was divided into cranial (C2 to apex) and caudal (apex to T2) arches postoperatively. A cervical lordosis distribution index(CLDI) was developed by dividing the cranial lordotic arch(C2 to apex) by the total segment(C2-T2) and multiplying by 100. Cross-tabulations developed categories for CLDI producing the highest chi-square values for achieving Optimal Outcome at two years and outcomes were assessed by multivariable analysis controlling for significant confounders., Results: 84 CD patients were included. Cervical apex distribution postoperatively was: 1% C3, 42% C4, 30% C5, 27% C6. Mean cervical LDI was 117±138. Mean cranial lordosis was 23.2±12.5°. Using cross-tabulations, a CLDI between 70 and 90 was defined as 'Aligned'. Chi-square test revealed significant differences among CLDI categories for DJK, DJF, Good Clinical Outcome, and Optimal Outcome(all P<0.05). Patients aligned in CLDI were less likely to develop DJK(OR: 0.1, [0.01-0.88]), more like to achieve GCO (OR: 3.9, [1.2-13.2]) and Optimal Outcome (OR: 7.9, [2.1-29.3] at two years. Patients aligned in CLDI developed DJF at a rate of 0%., Conclusion: The cervical lordosis distribution index, classified through the cranial segment, takes each unique cervical apex into account and tailors correction to the patient in order to better achieve good clinical outcomes and minimize catastrophic complications following cervical deformity surgery., Level of Evidence: III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Accreditation has been implemented in general practice in many countries as a tool for quality improvement. Evidence of the effects of accreditation is, however, lacking., Aim: To investigate the clinical effects of accreditation in general practice., Design and Setting: A mandatory national accreditation programme in Danish general practice was rolled out from 2016 to 2018. General practices were randomized to year of accreditation at the municipality level., Methods: We conducted a pragmatic randomized controlled study with general practices randomized to accreditation in 2016 (intervention group) and 2018 (control group). Data on patients enlisted with these practices were collected at baseline in 2014 (before randomization) and at follow-up in 2017. We use linear and logistic regression models to compare differences in changes in outcomes from baseline to follow-up between the intervention and control groups. The primary outcome was the number of redeemed medications. Secondary outcomes were polypharmacy, nonsteroidal anti-inflammatory drugs (NSAIDs) without proton pump inhibitors, sleeping medicine, preventive home visits, annual controls, spirometry tests, and mortality., Results: We found statistically significant effects of accreditation on the primary outcome, the number of redeemed medications, and the secondary outcome, polypharmacy. No other effects were detected., Conclusion: In this first randomized study exploring the effects of accreditation in a primary care context, accreditation was found to reduce the number of redeemed medications and polypharmacy. We conclude that accreditation can be effective in changing behaviour, but the identified effects are small and limited to certain outcomes. Evaluations on the cost-effectiveness of accreditation are therefore warranted., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Our understanding of the relationship between sagittal alignment and mechanical complications is evolving. In normal spines, the L1-pelvic angle (L1PA) accounts for the magnitude and distribution of lordosis and is strongly associated with pelvic incidence (PI), and the T4-pelvic angle (T4PA) is within 4° of the L1PA. We aimed to examine the clinical implications of realignment to a normal L1PA and T4-L1PA mismatch., Methods: A prospective multicenter adult spinal deformity registry was queried for patients who underwent fixation from the T1-T5 region to the sacrum and had 2-year radiographic follow-up. Normal sagittal alignment was defined as previously described for normal spines: L1PA = PI × 0.5 - 21°, and T4-L1PA mismatch = 0°. Mechanical failure was defined as severe proximal junctional kyphosis (PJK), displaced rod fracture, or reoperation for junctional failure, pseudarthrosis, or rod fracture within 2 years. Multivariable nonlinear logistic regression was used to define target ranges for L1PA and T4-L1PA mismatch that minimized the risk of mechanical failure. The relationship between changes in T4PA and changes in global sagittal alignment according to the C2-pelvic angle (C2PA) was determined using linear regression. Lastly, multivariable regression was used to assess associations between initial postoperative C2PA and patient-reported outcomes at 1 year, adjusting for preoperative scores and age., Results: The median age of the 247 included patients was 64 years (interquartile range, 57 to 69 years), and 202 (82%) were female. Deviation from a normal L1PA or T4-L1PA mismatch in either direction was associated with a significantly higher risk of mechanical failure, independent of age. Risk was minimized with an L1PA of PI × 0.5 - (19° ± 2°) and T4-L1PA mismatch between -3° and +1°. Changes in T4PA and in C2PA at the time of final follow-up were strongly associated (r2 = 0.96). Higher postoperative C2PA was independently associated with more disability, more pain, and worse self-image at 1 year., Conclusions: We defined sagittal alignment targets using L1PA (relative to PI) and the T4-L1PA mismatch, which are both directly modifiable during surgery. In patients undergoing long fusion to the sacrum, realignment based on these targets may lead to fewer mechanical failures., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The International Spine Study Group (ISSG) is funded through research grants from NuVasive, SI-Bone, DePuy Synthes Spine, K2M, Stryker, Biomet, AlloSource, and Orthofix, and individual donations. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I191)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Study Design: Multicenter, prospective cohort., Objectives: Malalignment following adult spine deformity (ASD) surgery can impact outcomes and increase mechanical complications. We assess whether preoperative goals for sagittal alignment following ASD surgery are achieved., Methods: ASD patients were prospectively enrolled based on 3 criteria: deformity severity (PI-LL ≥25°, TPA ≥30°, SVA ≥15 cm, TCobb≥70° or TLCobb≥50°), procedure complexity (≥12 levels fused, 3-CO or ACR) and/or age (>65 and ≥7 levels fused). The surgeon documented sagittal alignment goals prior to surgery. Goals were compared with achieved alignment on first follow-up standing radiographs., Results: The 266 enrolled patients had a mean age of 61.0 years (SD = 14.6) and 68% were women. Mean instrumented levels was 13.6 (SD = 3.8), and 23.2% had a 3-CO. Mean (SD) offsets (achieved-goal) were: SVA = -8.5 mm (45.6 mm), PI-LL = -4.6° (14.6°), TK = 7.2° (14.7°), reflecting tendencies to undercorrect SVA and PI-LL and increase TK. Goals were achieved for SVA, PI-LL, and TK in 74.4%, 71.4%, and 68.8% of patients, respectively, and was achieved for all 3 parameters in 37.2% of patients. Three factors were independently associated with achievement of all 3 alignment goals: use of PACs/equivalent for surgical planning ( P < .001), lower baseline GCA ( P = .009), and surgery not including a 3-CO ( P = .037)., Conclusions: Surgeons failed to achieve goal alignment of each sagittal parameter in ∼25-30% of ASD patients. Goal alignment for all 3 parameters was only achieved in 37.2% of patients. Those at greatest risk were patients with more severe deformity. Advancements are needed to enable more consistent translation of preoperative alignment goals to the operating room., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: reports consultancy fees from ZimVie, NuVasive, Cerapedics, and Carlsmed; receives royalties from Zimmer Biomet and Nuvasive; holds stock in Alphatec and NuVasive; receives research funding to his institution from DePuy Synthes, International Spine Study Group Foundation (ISSGF), and AOSpine; receives fellowship grant funding to his institution from AOSpine; serves on the Executive Committee of the ISSGF; and serves on the editorial boards of Journal of Neurosurgery Spine, Neurosurgery, Operative Neurosurgery, and Spine Deformity. is a consultant for ISSGF. is a consultant for Globus Medical and Alphatec; receives royalties from NuVasive; receives research support from ISSG; receives honoraria from DePuy Synthes, Stryker, and Implanet; and has leadership roles in ISSG and the Scoliosis Research Society. is a consultant for DePuy Synthes, Stryker, and Medtronic, SI Bone, and Agnovos; receives honoraria and a fellowship grant paid to an institution from AO Spine; and has leadership roles with AOSpine. Dr. Kim receives royalties from Zimmer Biomet, Acuity Surgical, and K2M-Stryker; is a consultant for NuVasive; receives research support from the ISSGF; is on advisory boards for Vivex Biology and Aspen Medical; and has other financial or non-financial interests with AOSpine. is a consultant for Medtronic, SpineWave, Terumo, and Royal Biologics; receives honoraria from Cervical Spine Research Society, Globus Medical, and Zimmer; serves on the editorial or governing board for Spine journal; and receives research support from Allosource. receives research support from Stryker, Biom’Up, Pfizer, the Alan L. & Jacqueline B. Stuart Spine Center, National Health Foundation, Cerapedics, Empirical Spine, Inc., TSRH, and Scoliosis Research Society; receives royalties from Acuity, Medtronic, and NuVasive; is a consultant for Acuity, DePuy, Medtronic, NuVasive, FYR Medical, and Stryker; receives honoraria from Baxter, Broadwater, NASS, and Pacira Pharmaceuticals; holds patents with Medtronic; participates on a data safety monitoring board or advisory board with Medtronic; has a leadership role in the National Spine Health Foundation; owns stock/stock options in Cingulate Therapeutics and FYR Medical; is an employee of Norton Healthcare, Inc.; and serves as a journal reviewer for Global Spine Journal, Spine Deformity, and The Spine Journal. and receives research/fellowship support from NuVasive, Medtronic, SeaSpine, SI Bone, and AONA; receives royalties from SI Bone, Nuvasive, Seaspine, Aesculap, and Globus Medical; is a consultant for Aesculap, NuVasive, SI Bone, SeaSpine, Spinal Elements, Biedermann-Motech, Silony, Neo Medical, Depuy, Medtronic, Carevature, and ControlRad; has received payment/honoraria from Radius; has patents with Globus, Spine Innovation, and SI Bone; has leadership role with San Diego Spine Foundation; and has stock/stock options with Alphatec, Nuvasive, Seaspine, and SI Bone. receives grants/research support from Medtronic and Orthofix; receives royalties from Spineart and Stryker; is a consultant for Stryker Spine, Spineart, and Medtronic; and has received payment for expert testimony from multiple law firms. is a consultant for NuVasive, Viseon, Carlsmed, SI Bone, and SeaSpine; holds patents with Stryker, NuVasive, and SeaSpine; has leadership roles with Global Spine Outreach and San Diego Spine Foundation; has stock or stock options with Alphatec, SeaSpine, and NuVasive; and receives royalties from NuVasive and K2M/Stryker. is a consultant for Globus, NuVasive, and Medtronic; receives royalties from Altus; receives grants from Medtronic; and has stock or stock options from One Point Surgical. Dr. receives travel expenses to teach at the ISSG-Medtronic Spine Course for fellows and residents; and has a leadership role with the Canadian Spine Society. receives grants/research support from Prosydiuan and NuVasive. receives honoraria from Wolters Kluwer; received support for travel from AO Spine; has leadership roles with Scoliosis Research Society and AO Spine; and receives research support from the Setting Scoliosis Straight Foundation and San Diego Spine Foundation. is a consultant for Stryker Spine; receives grant/research support from Medtronic, DePuy Synthes, and AOSpine; receives honoraria from Medtronic, Stryker Spine, DePuy Synthes, Scoliosis Research Society, and AOSpine; receives support for travel from AO Spine and Scoliosis Research Society; and is on an advisory board/panel for AOSpine Research Commission and Scoliosis Research Society Research Task Force; and is Chair of the AO Spine Knowledge Forum Deformity. owns stock in J&J; is a consultant for DePuy, Medtronic, Globus; receives royalties from Innomed, DePuy, and Globus; receives honoraria from AO Spine, Wright State, and LSU; serves on the board of directors of the Scoliosis Research Society; receives travel reimbursements from DePuy, Globus, Scoliosis Research Society; and has a voluntary relationship with the National Spine Health Foundation. is a consultant for MSD, Zimmer Biomet, and Mainstay Medical; receives royalties from Zimmer Biomet, Medtronic, and Stryker; owns stock in VFT Solutions and SeaSpine; is an executive committee member of ISSG. receives royalties from DePuy Spine, Globus, and Blue Ocean Spine; is a consultant for DePuy Spine, Globus, and Blue Ocean Spine; has a leadership role in the Scoliosis Research Society and International Spine Study Group Foundation; has stock or stock options in Progenerative Medical; and has received research support from DePuy Spine and ISSGF. receives royalties from Stryker, Biomet Zimmer Spine, DePuy Synthes, NuVasive, Next Orthosurgical, K2M, and Medicrea; is a consultant for DePuy Synthes, Medtronic, Medicrea, K2M, Agada Medical, and Carlsmed; receives research support from Titan Spine, DePuy Synthes, and ISSG; serves on the editorial board of Operative Neurosurgery; receives grant funding from SRS; serves on the executive committee of ISSG; is the director of Global Spinal Analytics; and is the safety and value committee chair of SRS. is a consultant for Medtronic, ABRYX, and Acuity Surgical; receives research/grant support from AOSpine, Scoliosis Research Society, and Setting Scoliosis Straight Foundation; receives royalties from Medtronic and Acuity Surgical; and receives other financial support from Broadwater, AOSpine, and Scoliosis Research Society. is a consultant for NuVasive, SI Bone, and Proprio; owns stock in NuVasive; holds patents with NuVasive; receives fellowship funding from Globus, Medtronic, and NuVasive; and receives royalties from NuVasive, Medtronic, and SI Bone; has leadership roles with SRS and CSRS; and receives study-related clinical or research support from DePuy Synthes and ISSGF. is a consultant for Zimmer Biomet, NuVasive, Cerapedics, Carlsmed, SeaSpine, and DePuy Synthes; owns stock in Alphatec and NuVasive; receives study-related clinical or research support from DePuy Synthes and ISSGF; receives non–study-related clinical or research support from DePuy Synthes, ISSGF, and AO Spine; receives royalties from Zimmer Biomet and NuVasive; and receives fellowship support from AO Spine. is a consultant for Alphatec, Stryker, and MiRus; receives honoraria from Stryker; holds patents with Stryker; receives study-related clinical or research support from Medtronic, Globus, NuVasive, Stryker, Carlsmed, and SI Bone; receives non–study-related clinical or research support from DePuy Synthes; and receives royalties from Stryker and NuVasive. report no conflicts of interest.

Knowledge about the molecular mechanisms underlying the systemic inflammation observed in psoriasis remains incomplete. In this study, we applied mass spectrometry-based proteomics to compare the plasma protein levels between patients with psoriasis and healthy individuals, aiming to unveil potential systemically dysregulated proteins and pathways associated with the disease. Plasma samples from adult patients with moderate-to-severe psoriasis vulgaris (N = 59) and healthy age- and sex-matched individuals (N = 21) were analyzed using liquid chromatography-tandem mass spectrometry. Patients did not receive systemic anti-psoriatic treatment for four weeks before inclusion. A total of 776 protein groups were quantified. Of these, 691 were present in at least 60% of the samples, providing the basis for the downstream analysis. We identified 20 upregulated and 22 downregulated proteins in patients with psoriasis compared to controls ( p < 0.05). Multiple proteins from the complement system were upregulated, including C2, C4b, C5, and C9, and pathway analysis revealed enrichment of proteins involved in complement activation and formation of the terminal complement complex. On the other end of the spectrum, periostin was the most downregulated protein in sera from patients with psoriasis. This comprehensive proteomic investigation revealed significantly elevated levels of complement cascade proteins in psoriatic plasma, which might contribute to increased systemic inflammation in patients with psoriasis.

Study Design: A retrospective cohort study of a prospectively collected multicenter adult spinal deformity (ASD) database., Objective: The aim of this study was to compare staged procedures to same-day interventions and identify the optimal time interval between staged surgeries for the treatment of ASD., Background: Surgical intervention for ASD is an invasive and complex procedure that surgeons often elect to perform on different days (staging). Yet, there remains a paucity of literature on the timing and effects of the interval between stages., Materials and Methods: ASD patients with 2-year data undergoing an anterior/posterior (A/P) fusion to the ilium were included. Propensity score matching was performed for the number of levels fused, number of interbody devices, surgical approaches, number of osteotomies/three-column osteotomy, frailty, Oswestry Disability Index, Charlson Comorbidity Index, revisions, sagittal vertical axis, pelvic incidence-lumbar lordosis, and upper instrumented vertebrae to create balanced cohorts of same-day and staged surgical patients. Staged patients were stratified by intervening time-period between surgeries, using quartiles., Results: A total of 176 propensity score-matched patients were included. The median interval between A/P staged procedures was 3 days. Staged patients had greater operative time and lower intensive care unit stays postoperatively ( P <0.05). At 2 years, staged compared with same-day showed a greater improvement in T1 slope-cervical lordosis, C2 sacral slope, and SRS-Schwab sagittal vertical axis ( P <0.05). Staged patients had higher rates of minimal clinically important difference for 1-year SRS-Appearance and 2-year Physical Component Summary scores. Assessing different intervals of staging, patients at the 75th percentile interval showed greater improvement in 1-year SRS-Pain and SRS-Total postoperative as well as SRS-Activity, Pain, Satisfaction, and Total scores ( P <0.05) compared with patients in lower quartiles. Compared with the 25th percentile, patients reaching the 50th percentile interval were associated with increased odds of improvement in Global Alignment and Proportion score proportionality [9.3 (1.6-53.2), P =0.01]., Conclusions: This investigation is among the first to compare multicenter staged and same-day surgery A/P ASD patients fused to ilium using propensity matching. Staged procedures resulted in significant improvement radiographically, reduced intensive care unit admissions, and superior patient-reported outcomes compared with same-day procedures. An interval of at least 3 days between staged procedures is associated with superior outcomes in terms of Global Alignment and Proportion score proportionality., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To develop a simplified, modified frailty index for adult spinal deformity (ASD) patients dependent on objective clinical factors., Methods: ASD patients with baseline (BL) and 2-year (2Y) follow-up were included. Factors with the largest R 2 value derived from multivariate forward stepwise regression were including in the modified ASD-FI (clin-ASD-FI). Factors included in the clin-ASD-FI were regressed against mortality, extended length of hospital stay (LOS, > 8 days), revisions, major complications and weights for the clin-ASD-FI were calculated via Beta/Sullivan. Total clin-ASD-FI score was created with a score from 0 to 1. Linear regression correlated clin-ASD-FI with ASD-FI scores and published cutoffs for the ASD-FI were used to create the new frailty cutoffs: not frail (NF: < 0.11), frail (F: 0.11-0.21) and severely frail (SF: > 0.21). Binary logistic regression assessed odds of complication or reop for frail patients., Results: Five hundred thirty-one ASD patients (59.5 yrs, 79.5% F) were included. The final model had a R 2 of 0.681, and significant factors were: < 18.5 or > 30 BMI (weight: 0.0625 out of 1), cardiac disease (0.125), disability employment status (0.3125), diabetes mellitus (0.0625), hypertension (0.0625), osteoporosis (0.125), blood clot (0.1875), and bowel incontinence (0.0625). These factors calculated the score from 0 to 1, with a mean cohort score of 0.13 ± 0.14. Breakdown by clin-ASD-FI score: 51.8% NF, 28.1% F, 20.2% SF. Increasing frailty severity was associated with longer LOS (NF: 7.0, F: 8.3, SF: 9.2 days; P < 0.001). Frailty independently predicted occurrence of any complication (OR: 9.357 [2.20-39.76], P = 0.002) and reop (OR: 2.79 [0.662-11.72], P = 0.162)., Conclusions: Utilizing an existing ASD frailty index, we proposed a modified version eliminating the patient-reported components. This index is a true assessment of physiologic status, and represents a superior risk factor assessment compared to other tools for both primary and revision spinal deformity surgery as a result of its immutability with surgery, lack of subjectivity, and ease of use., (© 2024. The Author(s), under exclusive licence to Scoliosis Research Society.)

Objective: Complex spinal deformity surgeries may involve significant blood loss. The use of antifibrinolytic agents such as tranexamic acid (TXA) has been proven to reduce perioperative blood loss. However, for patients with a history of thromboembolic events, there is concern of increased risk when TXA is used during these surgeries. This study aimed to assess whether TXA use in patients undergoing complex spinal deformity correction surgeries increases the risk of thromboembolic complications based on preexisting thromboembolic risk factors., Methods: Data were analyzed for adult patients who received TXA during surgical correction for spinal deformity at 21 North American centers between August 2018 and October 2022. Patients with preexisting thromboembolic events and other risk factors (history of deep venous thrombosis [DVT], pulmonary embolism [PE], myocardial infarction [MI], stroke, peripheral vascular disease, or cancer) were identified. Thromboembolic complication rates were assessed during the postoperative 90 days. Univariate and multivariate analyses were performed to assess thromboembolic outcomes in high-risk and low-risk patients who received intravenous TXA., Results: Among 411 consecutive patients who underwent complex spinal deformity surgery and received TXA intraoperatively, 130 (31.6%) were considered high-risk patients. There was no significant difference in thromboembolic complications between patients with and those without preexisting thromboembolic risk factors in univariate analysis (high-risk group vs low-risk group: 8.5% vs 2.8%, p = 0.45). Specifically, there were no significant differences between groups regarding the 90-day postoperative rates of DVT (high-risk group vs low-risk group: 1.5% vs 1.4%, p = 0.98), PE (2.3% vs 1.8%, p = 0.71), acute MI (1.5% vs 0%, p = 0.19), or stroke (0.8% vs 1.1%, p > 0.99). On multivariate analysis, high-risk status was not a significant independent predictor for any of the thromboembolic complications., Conclusions: Administration of intravenous TXA during the correction procedure did not change rates of thromboembolic events, acute MI, or stroke in this cohort of adult spinal deformity surgery patients.

Background and Objectives: Achieving spinopelvic realignment during adult spinal deformity (ASD) surgery does not always produce ideal outcomes. Little is known whether compensation in lower extremities (LEs) plays a role in this disassociation. The objective is to analyze lower extremity compensation after complex ASD surgery, its effect on outcomes, and whether correction can alleviate these mechanisms., Methods: We included patients with complex ASD with 6-week data. LE parameters were as follows: sacrofemoral angle, knee flexion angle, and ankle flexion angle. Each parameter was ranked, and upper tertile was deemed compensation. Patients compensating and not compensating postoperatively were propensity score matched for body mass index, frailty, and T1 pelvic angle. Linear regression assessed correlation between LE parameters and baseline deformity, demographics, and surgical details. Multivariate analysis controlling for baseline deformity and history of total knee/hip arthroplasty evaluated outcomes., Results: Two hundred and ten patients (age: 61.3 ± 14.1 years, body mass index: 27.4 ± 5.8 kg/m2, Charlson Comorbidity Index: 1.1 ± 1.6, 72% female, 22% previous total joint arthroplasty, 24% osteoporosis, levels fused: 13.1 ± 3.8) were included. At baseline, 59% were compensating in LE: 32% at hips, 39% knees, and 36% ankles. After correction, 61% were compensating at least one joint. Patients undercorrected postoperatively were less likely to relieve LE compensation (odds ratio: 0.2, P = .037). Patients compensating in LE were more often undercorrected in age-adjusted pelvic tilt, pelvic incidence, lumbar lordosis, and T1 pelvic angle and disproportioned in Global Alignment and Proportion (P < .05). Patients matched in sagittal age-adjusted score at 6 weeks but compensating in LE were more likely to develop proximal junctional kyphosis (odds ratio: 4.1, P = .009) and proximal junctional failure (8% vs 0%, P = .035) than those sagittal age-adjusted score-matched and not compensating in LE., Conclusion: Perioperative lower extremity compensation was a product of undercorrecting complex ASD. Even in age-adjusted realignment, compensation was associated with global undercorrection and junctional failure. Consideration of lower extremities during planning is vital to avoid adverse outcomes in perioperative course after complex ASD surgery., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Innate lymphoid cells (ILCs) are essential players in the skin-associated immune system, nevertheless little is known about their proteomes and proteomic diversity. In this study, we describe about 6,600 proteins constitutively expressed by ILC2s and ILC3s from healthy human skin and blood using state-of-the-art proteomics. Although the vast majority of proteins was expressed by both ILC subsets and in both compartments, the skin ILC2s and ILC3s were more distinct than their counterparts in blood. Only skin ILC3s expressed uniquely detected proteins. Our in-depth proteomic dataset allowed us to define the cluster of differentiation marker profiles of the ILC subsets, explore distribution and abundance of proteins known to have immunological functions, as well as identify subset-specific proteins that have not previously been implicated in ILC biology. Taken together, our analyses substantially expand understanding of the protein expression signatures of ILC subsets. Going forward, these proteomic datasets will serve as valuable resources for future studies of ILC biology., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Design/setting: This was a retrospective cohort study., Background: Little is known of the intersection between surgical invasiveness, cervical deformity (CD) severity, and frailty., Objective: The aim of this study was to investigate the outcomes of CD surgery by invasiveness, frailty status, and baseline magnitude of deformity., Methods: This study included CD patients with 1-year follow-up. Patients stratified in high deformity if severe in the following criteria: T1 slope minus cervical lordosis, McGregor's slope, C2-C7, C2-T3, and C2 slope. Frailty scores categorized patients into not frail and frail. Patients are categorized by frailty and deformity (not frail/low deformity; not frail/high deformity; frail/low deformity; frail/high deformity). Logistic regression assessed increasing invasiveness and outcomes [distal junctional failure (DJF), reoperation]. Within frailty/deformity groups, decision tree analysis assessed thresholds for an invasiveness cutoff above which experiencing a reoperation, DJF or not achieving Good Clinical Outcome was more likely., Results: A total of 115 patients were included. Frailty/deformity groups: 27% not frail/low deformity, 27% not frail/high deformity, 23.5% frail/low deformity, and 22.5% frail/high deformity. Logistic regression analysis found increasing invasiveness and occurrence of DJF [odds ratio (OR): 1.03, 95% CI: 1.01-1.05, P =0.002], and invasiveness increased with deformity severity ( P <0.05). Not frail/low deformity patients more often met Optimal Outcome with an invasiveness index <63 (OR: 27.2, 95% CI: 2.7-272.8, P =0.005). An invasiveness index <54 for the frail/low deformity group led to a higher likelihood of meeting the Optimal Outcome (OR: 9.6, 95% CI: 1.5-62.2, P =0.018). For the frail/high deformity group, patients with a score <63 had a higher likelihood of achieving Optimal Outcome (OR: 4.8, 95% CI: 1.1-25.8, P =0.033). There was no significant cutoff of invasiveness for the not frail/high deformity group., Conclusions: Our study correlated increased invasiveness in CD surgery to the risk of DJF, reoperation, and poor clinical success. The thresholds derived for deformity severity and frailty may enable surgeons to individualize the invasiveness of their procedures during surgical planning to account for the heightened risk of adverse events and minimize unfavorable outcomes., Competing Interests: P.G.P.: Allosource: Other financial or material support; Cervical Scoliosis Research Society: Research support; Globus Medical: Paid presenter or speaker; Medtronic: Paid consultant; Royal Biologics: Paid consultant; Spine: Editorial or governing board; SpineWave: Paid consultant; Terumo: Paid consultant; Zimmer: Paid presenter or speaker. V.L.: DePuy, A Johnson & Johnson Company: Paid presenter or speaker; European Spine Journal : Editorial or governing board; Globus Medical: Paid consultant; International Spine Study Group: Board or committee member; Nuvasive: IP royalties; Scoliosis Research Society: Board or committee member; The Permanente Medical Group: Paid presenter or speaker. R.F.: Nemaris: Stock or stock options. H.J.K.: AAOS: Board or committee member; Alphatec Spine: Paid consultant; AO SPINE: Board or committee member; Cervical Spine Research Society: Board or committee member; HSS Journal , Asian Spine Journal : Editorial or governing board; ISSGF: Research support; K2M: IP royalties; Scoliosis Research Society: Board or committee member; Zimmer: IP royalties. A.H.D.: EOS: Paid consultant; Medicrea: Paid consultant; Medtronic Sofamor Danek: Paid consultant; Novabone: Paid consultant; Orthofix Inc.: Paid consultant; Research support; Southern Spine: IP royalties; Spineart: IP royalties; Paid consultant; Springer: Publishing royalties, financial or material support; Stryker: Paid consultant. J.L.G.: Acuity: IP royalties; Paid consultant; Alan L. & Jacqueline B. Stuart Spine Research: Research support; Cerapedics: Research support; Cingulate Therapeutics: Stock or stock Options; DePuy, A Johnson & Johnson Company: Paid presenter or speaker; Global Spine Journal —Reviewer: Editorial or governing board; Intellirod Spine Inc.: Research support; K2M /Stryker: Board or committee member; MAZOR Surgical Technologies: Paid consultant; Medtronic: Board or committee member; Paid consultant; Research support; Norton Healthcare: Research support; Nuvasive: IP royalties; Paid consultant; Pfizer: Research support; Scoliosis Research Society: Research support; Spine Deformity —Reviewer: Editorial or governing board; Stryker: Paid consultant; Paid presenter or speaker; Texas Scottish Rite Hospital: Research support; The Spine Journal —Reviewer: Editorial or governing board. T.S.P.: Altus: IP royalties; Globus Medical: Paid consultant; Medicrea: Paid consultant; Medtronic: Paid consultant; Nuvasive: Paid consultant; Spine Align: Stock or stock Options; Stryker: Paid consultant; Torus Medical: Stock or stock Options. G.M.M.: Carlsmed: Paid consultant; ISSGF: Research support; K2M: IP royalties; Nuvasive: IP royalties; Paid consultant; Research support; Scoliosis Research Society: Board or committee member; SeaSpine: Paid consultant; Stryker: Paid consultant; Viseon: Paid consultant. R.K.E.: Aesculap/B.Braun: Paid consultant; Alphatec Spine: Stock or stock Options; Baxter: Paid consultant; Biedermann-Motech: Paid consultant; Carevature: Paid consultant; Stock or stock Options; Globus Medical: IP royalties; Invuity: Stock or stock Options; Medtronic: Paid consultant; Nocimed: Stock or stock Options; Nuvasive: IP royalties; Paid consultant; Research support; Stock or stock Options; Radius: Paid presenter or speaker; San Diego Spine Foundation: Board or committee member; Scoliosis Research Society: Board or committee member; Seaspine: IP royalties; Paid consultant; Stock or stock Options; SI Bone: IP royalties; Paid consultant; Society of Lateral Access Surgery: Board or committee member; Spine Innovations: Stock or stock Options; Stryker: Paid consultant. K.H.: European Spine Journal : Editorial or governing board; Nuvasive: Research support. E.O.K.: AO Spine: Paid presenter or speaker; Research support; DePuy, A Johnson & Johnson Company: Paid consultant; Medicrea: Paid consultant; Medtronic: Paid consultant; Stryker: Paid consultant. B.G.L.: ISSGF: Paid consultant. R.A.H.: American Orthopaedic Association: Board or committee member; Cervical Spine Research Society: Board or committee member; DePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Paid presenter or speaker; Globus Medical: IP royalties; Paid consultant; Paid presenter or speaker; International Spine Study Group: Board or committee member; ISSLS Textbook of the Lumbar Spine: Editorial or governing board; Medtronic: Paid consultant; Paid presenter or speaker; North American Spine Society: Board or committee member; Orthofix Inc.: Paid consultant; Paid presenter or speaker; Scoliosis Research Society: Board or committee member; SeaSpine: IP royalties; Spine Connect: Stock or stock Options; Western Ortho Assn: Board or committee member. D.C.B.: Bioventus: Research support; DePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Research support; Pfizer: Research support; Progenerative Medical: Stock or stock Options; Scoliosis Research Society: Board or committee member; Spine Deformity : Editorial or governing board. P.V.M.: AANS/CNS Spine Section and Scoliosis Research Society: Board or committee member; American Association of Neurological Surgeons: Board or committee member; Cervical Spine Research Society: Board or committee member; Congress of Neurological Surgeons: Board or committee member; DePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Global Spine Journal : Editorial or governing board; Globus Medical: Paid consultant; International Spine Study Group: Research support; Neurosurgery: Editorial or governing board; NREF: Research support; Spinal Deformity: Editorial or governing board; Spinicity/ISD: Stock or stock Options; Springer: Publishing royalties, financial or material support; Stryker: Paid consultant; Taylor and Francis: Publishing royalties, financial or material support; Thieme: Publishing royalties, financial or material support; World Neurosurgery: Editorial or governing board. P.P.: AANS Spine Section: Board or committee member; Cerapedics: Research support; DePuy, A Johnson & Johnson Company: Research support; Globus Medical: IP royalties; Paid consultant; ISSG: Research support; Journal of Neurosurgery Spine : Editorial or governing board; Neurosurgery: Editorial or governing board; North American Spine Society: Board or committee member; Nuvasive: Paid consultant; Operative Neurosurgery: Editorial or governing board; Scoliosis Research Society: Board or committee member; SI-Bone: Research support. F.J.S.: DePuy, A Johnson & Johnson Company: Research support; Globus Medical: Paid consultant; Paid presenter or speaker; K2M: IP royalties; Paid consultant; Paid presenter or speaker; Medicrea: Paid consultant; Medtronic: Paid consultant; Medtronic Sofamor Danek: IP royalties; Paid presenter or speaker; Nuvasive: Research support; Scoliosis Research Society: Board or committee member; Spine Deformity : Editorial or governing board; Stryker: Research support; VP of International Spine Society Group (ISSG): Board or committee member; Zimmer: IP royalties; Paid consultant; Paid presenter or speaker. D.C.: Globus Medical: IP royalties; Paid consultant. C.I.S.: AANS: Board or committee member; Cervical Spine Research Society: Board or committee member; DePuy, A Johnson & Johnson Company: Paid presenter or speaker; Research support; Globus Medical: Research support; Medtronic: Other financial or material support; Paid consultant; Medtronic Sofamor Danek: IP royalties; Paid presenter or speaker; Research support; Neurosurgery RRC: Board or committee member; Nuvasive: IP royalties; Paid consultant; Paid presenter or speaker; Research support; Stock or stock Options; Proprio: Paid consultant; Scoliosis Research Society: Board or committee member; SI Bone: IP royalties; Spinal Deformity: Editorial or governing board; Spine: Editorial or governing board. R.S.B.: allosource: Paid consultant; Research support; Biomet: Research support; DePuy, A Johnson & Johnson Company: Paid consultant; Research support; EOS: Research support; Globus Medical: Research support; k2 medical: IP royalties; Paid consultant; Paid presenter or speaker; Research support; Medtronic Sofamor Danek: Research support; North American Spine Society: Board or committee member; Nuvasive: IP royalties; Research support; Orthofix Inc.: Research support; Scoliosis Research Society: Board or committee member; Stryker: IP royalties; Paid presenter or speaker. C.P.A.: Biomet Spine: IP royalties; DePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Research support; Global Spine Analytics—Director: Other financial or material support; International Spine Study Group (ISSG): Research support; International Spine Study Group (ISSG)—Executive Committee: Other financial or material support; K2M: IP royalties; Paid consultant; Medicrea: IP royalties; Paid consultant; Medtronic: Paid consultant; Next Orthosurgical: IP royalties; Nuvasive: IP royalties; Operative Neurosurgery—Editorial Board: Other financial or material support; Scoliosis Research Society (SRS)—Grant Funding: Other financial or material support; Stryker: IP royalties; Titan Spine: Research support. J.S.S.: Alphatec Spine: Stock or stock Options; Carlsmed: Paid consultant; Cerapedics: Paid consultant; DePuy: Research support; DePuy, A Johnson & Johnson Company: Paid consultant; Journal of Neurosurgery Spine : Editorial or governing board; Neurosurgery: Editorial or governing board; Nuvasive: IP royalties; Paid consultant; Research support; Operative Neurosurgery: Editorial or governing board; Scoliosis Research Society: Board or committee member; Spine Deformity : Editorial or governing board; Stryker: Paid consultant; Thieme: Publishing royalties, financial or material support; Zimmer: IP royalties; paid consultant. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Roussouly, SRS-Schwab, and Global Alignment and Proportion (GAP) classifications define alignment by spinal shape and deformity severity. The efficacy of different surgical approaches and techniques to successfully achieve these goals is not well understood., Purpose: Identify the impact of surgical approach and/or technique on meeting complex realignment goals in adult spinal deformity (ASD) corrective surgery., Study Design/setting: Retrospective study., Materials and Methods: Included patients with ASD fused to pelvis with 2-year data. Patients were categorized by: (1) Roussouly: matching current and theoretical spinal shapes, (2) improving in SRS-Schwab modifiers (0, +, ++), and (3) improving GAP proportionality by 2 years. Analysis of covariance and multivariable logistic regression analyses controlling for age, levels fused, baseline deformity, and 3-column osteotomy usage compared the effect of different surgical approaches, interbody, and osteotomy use on meeting realignment goals., Results: A total of 693 patients with ASD were included. By surgical approach, 65.7% were posterior-only and 34.3% underwent anterior-posterior approach with 76% receiving an osteotomy (21.8% 3-column osteotomy). By 2 years, 34% matched Roussouly, 58% improved in GAP, 45% in SRS-Schwab pelvic tilt (PT), 62% sagittal vertical axis, and 70% pelvic incidence-lumbar lordosis. Combined approaches were most effective for improvement in PT [odds ratio (OR): 1.7 (1.1-2.5)] and GAP [OR: 2.2 (1.5-3.2)]. Specifically, anterior lumbar interbody fusion (ALIF) below L3 demonstrated higher rates of improvement versus TLIFs in Roussouly [OR: 1.7 (1.1-2.5)] and GAP [OR: 1.9 (1.3-2.7)]. Patients undergoing pedicle subtraction osteotomy at L3 or L4 were more likely to improve in PT [OR: 2.0 (1.0-5.2)] and pelvic incidence-lumbar lordosis [OR: 3.8 (1.4-9.8)]. Clinically, patients undergoing the combined approach demonstrated higher rates of meeting SCB in Oswestry Disability Index by 2 years while minimizing rates of proximal junctional failure, most often with an ALIF at L5-S1 [Oswestry Disability Index-SCB: OR: 1.4 (1.1-2.0); proximal junctional failure: OR: 0.4 (0.2-0.8)]., Conclusions: Among patients undergoing ASD realignment, optimal lumbar shape and proportion can be achieved more often with a combined approach. Although TLIFs, incorporating a 3-column osteotomy, at L3 and L4 can restore lordosis and normalize pelvic compensation, ALIFs at L5-S1 were most likely to achieve complex realignment goals with an added clinical benefit and mitigation of junctional failure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design/setting: Retrospective cohort study., Objective: Assess the extent to which defined risk factors of adverse events are drivers of cost-utility in spinal deformity (ASD) surgery., Methods: ASD patients with 2-year (2Y) data were included. Tertiles were used to define high degrees of frailty, sagittal deformity, blood loss, and surgical time. Cost was calculated using the Pearl Diver registry and cost-utility at 2Y was compared between cohorts based on the number of risk factors present. Statistically significant differences in cost-utility by number of baseline risk factors were determined using ANOVA, followed by a generalized linear model, adjusting for clinical site and surgeon, to assess the effects of increasing risk score on overall cost-utility., Results: By 2 years, 31% experienced a major complication and 23% underwent reoperation. Patients with ≤2 risk factors had significantly less major complications. Patients with 2 risk factors improved the most from baseline to 2Y in ODI. Average cost increased by $8234 per risk factor (R 2 = .981). Cost-per-QALY at 2Y increased by $122,650 per risk factor (R 2 = .794). Adjusted generalized linear model demonstrated a significant trend between increasing risk score and increasing cost-utility (r 2 = .408, P < .001)., Conclusions: The number of defined patient-specific and surgical risk factors, especially those with greater than two, were associated with increased index surgical costs and diminished cost-utility. Efforts to optimize patient physiology and minimize surgical risk would likely reduce healthcare expenditures and improve the overall cost-utility profile for ASD interventions. Level of evidence: III., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter Gust Passias, MDAllosource: Other financial or material support Cervical Scoliosis Research Society: Research support Globus Medical: Paid presenter or speaker Medtronic: Paid consultant Royal Biologics: Paid consultant Spine: Editorial or governing board SpineWave: Paid consultant Terumo: Paid consultant Zimmer: Paid presenter or speaker. Virginie Lafage, PhD DePuy, A Johnson & Johnson Company: Paid presenter or speaker European Spine Journal: Editorial or governing board Globus Medical: Paid consultant International Spine Study Group: Board or committee member Nuvasive: IP royalties Scoliosis Research Society: Board or committee member The Permanente Medical Group: Paid presenter or speaker. Ferran Pellise, MDAOSpine Deformity Knowledge Forum: Board or committee member DePuy, A Johnson & Johnson Company: Research support European Spine Journal: Editorial or governing board EuroSpine, The Spine Society of Europe: Board or committee member Medtronic: Paid consultant; Research support Scoliosis Research Society: Board or committee member Spanish Spine Society, GEER: Board or committee member Stryker: Paid consultant. Renaud Lafage, MS Nemaris: Stock or stock Options. Munish C Gupta, MD. AO Spine Faculty, travel: Board or committee memberDePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Paid presenter or speaker European Spine Journal-Advisory Board: Editorial or governing board Global Spine Journal-Reviewer: Editorial or governing board Globus Medical: IP royalties; Paid consultant honorarium for faculty: Board or committee member Innomed: IP royalties Johnson & Johnson: Stock or stock Options Medtronic: Paid consultant Spine Deformity, Reviewer: Editorial or governing board SRS-Board of Directors: Board or committee member SRS-IMAST & Education committee: Board or committee member travel: Board or committee member Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support. Michael Patrick Kelly, MD, MSc, AO Spine: Board or committee memberCervical Spine Research Society: Board or committee member Scoliosis Research Society: Board or committee member Spine: Editorial or governing board. Han Jo Kim, MDAAOS: Board or committee member Alphatec Spine: Paid consultant AO SPINE: Board or committee member Cervical Spine Research Society: Board or committee member HSS Journal, Asian Spine Journal: Editorial or governing board ISSGF: Research support K2M: IP royalties Scoliosis Research Society: Board or committee member Zimmer: IP royalties. Khaled M Kebaish, MDDePuy, A Johnson & Johnson Company: IP royalties; Paid consultant; Paid presenter or speaker; Research support Orthofix, Inc.: IP royalties; Paid consultant Orthofix, Inc., K2 medical Inc: Paid presenter or speaker Scoliosis Research Society: Board or committee member Stryker: IP royalties. 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Study Design: Retrospective cohort study., Objective: Understand the benefit of addressing malalignment in revision surgery for proximal junctional kyphosis (PJK)., Summary of Background Data: PJK is a common cause of revision surgery for adult spinal deformity patients. During a revision, surgeons may elect to perform a proximal extension of the fusion, or also correct the source of the lumbopelvic mismatch., Materials and Methods: Recurrent PJK following revision surgery was the primary outcome. Revision surgical strategy was the primary predictor (proximal extension of fusion alone compared with combined sagittal correction and proximal extension). Multivariable logistic regression determined rates of recurrent PJK between the two surgical groups with lumbopelvic surgical correction assessed through improving ideal alignment in one or more alignment criteria [Global Alignment and Proportionality (GAP), Roussouly-type, and Sagittal Age-Adjusted Score (SAAS)]., Results: A total of 151 patients underwent revision surgery for PJK. PJK occurred at a rate of 43.0%, and PJF at 12.6%. Patients proportioned in GAP postrevision had lower rates of recurrent PJK [23% vs. 42%; odds ratio (OR): 0.3, 95% confidence interval (CI): 0.1-0.8, P =0.024]. Following adjusted analysis, patients who were ideally aligned in one of three criteria (Matching in SAAS and/or Roussouly matched and/or achieved GAP proportionality) had lower rates of recurrent PJK (36% vs. 53%; OR: 0.4, 95% CI: 0.1-0.9, P =0.035) and recurrent PJF (OR: 0.1, 95% CI: 0.02-0.7, P =0.015). Patients ideally aligned in two of three criteria avoid any development of PJF (0% vs. 16%, P <0.001)., Conclusions: Following revision surgery for PJK, patients with persistent poor sagittal alignment showed increased rates of recurrent PJK compared with patients who had abnormal lumbopelvic alignment corrected during the revision. These findings suggest addressing the root cause of surgical failure in addition to proximal extension of the fusion may be beneficial., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Multicenter comparative cohort., Objective: Studies have shown markedly higher rates of complications and all-cause mortality following surgery for adult cervical deformity (ACD) compared with adult thoracolumbar deformity (ATLD), though the reasons for these differences remain unclear. Our objectives were to compare baseline frailty, disability, and comorbidities between ACD and complex ATLD patients undergoing surgery., Methods: Two multicenter prospective adult spinal deformity registries were queried, one ATLD and one ACD. Baseline clinical and frailty measures were compared between the cohorts., Results: 616 patients were identified (107 ACD and 509 ATLD). These groups had similar mean age (64.6 vs 60.8 years, respectively, P = .07). ACD patients were less likely to be women (51.9% vs 69.5%, P < .001) and had greater Charlson Comorbidity Index (1.5 vs .9, P < .001) and ASA grade (2.7 vs 2.4, P < .001). ACD patients had worse VR-12 Physical Component Score (PCS, 25.7 vs 29.9, P < .001) and PROMIS Physical Function Score (33.3 vs 35.3, P = .031). All frailty measures were significantly worse for ACD patients, including hand dynamometer (44.6 vs 55.6 lbs, P < .001), CSHA Clinical Frailty Score (CFS, 4.0 vs 3.2, P < .001), and Edmonton Frailty Scale (EFS, 5.15 vs 3.21, P < .001). Greater proportions of ACD patients were frail (22.9% vs 5.7%) or vulnerable (15.6% vs 10.9%) based on EFS ( P < .001)., Conclusions: Compared with ATLD patients, ACD patients had worse baseline characteristics on all measures assessed (comorbidities/disability/frailty). These differences may help account for greater risk of complications and all-cause mortality previously observed in ACD patients and facilitate strategies for better preoperative optimization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Retrospective review of a prospectively enrolled adult spinal deformity (ASD) database., Objective: To investigate what patient factors elevate the risk of sub-optimal outcomes after deformity correction., Background: Currently, it is unknown what factors predict a poor outcome after adult spinal deformity surgery, which may require increased preoperative consideration and counseling., Materials and Methods: Patients >18 yrs undergoing surgery for ASD(scoliosis≥20°, SVA≥5 cm, PT≥25°, or TK≥60°). An unsatisfactory outcome was defined by the following categories met at two years: (1) clinical: deteriorating in ODI at two years follow-up (2) complications/reoperation: having a reoperation and major complication were deemed high risk for poor outcomes postoperatively (HR). Multivariate analyses assessed predictive factors of HR patients in adult spinal deformity patients., Results: In all, 633 adult spinal deformity (59.9 yrs, 79% F, 27.7 kg/m 2, CCI: 1.74) were included. Baseline severe Schwab modifier incidence (++): 39.2% pelvic incidence and lumbar lordosis, 28.8% sagittal vertical axis, 28.9% PT. Overall, 15.5% of patients deteriorated in ODI by two years, while 7.6% underwent reoperation and had a major complication. This categorized 11 (1.7%) as HR. HR were more comorbid in terms of arthritis (73%), heart disease (36%), and kidney disease (18%), P <0.001. Surgically, HR had greater EBL (4431ccs) and underwent more osteotomies (91%), specifically Ponte(36%) and Three Column Osteotomies(55%), which occurred more at L2(91%). HR underwent more PLIFs (45%) and had more blood transfusion units (2641ccs), all P <0.050. The multivariate regression determined a combination of a baseline Distress and Risk Assessment Method score in the 75th percentile, having arthritis and kidney disease, a baseline right lower extremity motor score ≤3, cSVA >65 mm, C2 slope >30.2°, CTPA >5.5° for an R2 value of 0.535 ( P <0.001)., Conclusions: When addressing adult spine deformities, poor outcomes tend to occur in severely comorbid patients with major baseline psychological distress scores, poor neurologic function, and concomitant cervical malalignment., Competing Interests: P.G.P.: Cerapedics: Other financial or material support; Cervical Scoliosis Research Society: Research support; Globus Medical: Paid presenter or speaker; Medtronic: Paid consultant; Royal Biologics: Paid consultant; Spine: Editorial or governing board; Spinevision: Other financial or material support; SpineWave: Paid consultant; Terumo: Paid consultant; The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While reimbursement is centered on 90-day outcomes, many patients may still achieve optimal, long-term outcomes following adult spinal deformity (ASD) surgery despite transient short-term complications., Objective: Compare long-term clinical success and cost-utility between patients achieving optimal realignment and suboptimally aligned peers., Study Design/setting: Retrospective cohort study of a prospectively collected multicenter database., Methods: ASD patients with two-year (2Y) data included. Groups were propensity score matched (PSM) for age, frailty, body mass index (BMI), Charlson Comorbidity Index (CCI), and baseline deformity. Optimal radiographic criteria are defined as meeting low deformity in all three (Scoliosis Research Society) SRS-Schwab parameters or being proportioned in Global Alignment and Proportionality (GAP). Cost-per-QALY was calculated for each time point. Multivariable logistic regression analysis and ANCOVA (analysis of covariance) adjusting for baseline disability and deformity (pelvic incidence (PI), pelvic incidence minus lumbar lordosis (PI-LL)) were used to determine the significance of surgical details, complications, clinical outcomes, and cost-utility., Results: A total of 930 patients were considered. Following PSM, 253 "optimal" (O) and 253 "not optimal" (NO) patients were assessed. The O group underwent more invasive procedures and had more levels fused. Analysis of complications by two years showed that the O group suffered less overall major (38% vs. 52%, p = 0.021) and major mechanical complications (12% vs. 22%, p = 0.002), and less reoperations (23% vs. 33%, p = 0.008). Adjusted analysis revealed O patients more often met MCID (minimal clinically important difference) in SF-36 PCS, SRS-22 Pain, and Appearance. Cost-utility-adjusted analysis determined that the O group generated better cost-utility by one year and maintained lower overall cost and costs per QALY (both p < 0.001) at two years., Conclusions: Fewer late complications (mechanical and reoperations) are seen in optimally aligned patients, leading to better long-term cost-utility overall. Therefore, the current focus on avoiding short-term complications may be counterproductive, as achieving optimal surgical correction is critical for long-term success.

Importance: Electroencephalograms (EEGs) are a fundamental evaluation in neurology but require special expertise unavailable in many regions of the world. Artificial intelligence (AI) has a potential for addressing these unmet needs. Previous AI models address only limited aspects of EEG interpretation such as distinguishing abnormal from normal or identifying epileptiform activity. A comprehensive, fully automated interpretation of routine EEG based on AI suitable for clinical practice is needed., Objective: To develop and validate an AI model (Standardized Computer-based Organized Reporting of EEG-Artificial Intelligence [SCORE-AI]) with the ability to distinguish abnormal from normal EEG recordings and to classify abnormal EEG recordings into categories relevant for clinical decision-making: epileptiform-focal, epileptiform-generalized, nonepileptiform-focal, and nonepileptiform-diffuse., Design, Setting, and Participants: In this multicenter diagnostic accuracy study, a convolutional neural network model, SCORE-AI, was developed and validated using EEGs recorded between 2014 and 2020. Data were analyzed from January 17, 2022, until November 14, 2022. A total of 30 493 recordings of patients referred for EEG were included into the development data set annotated by 17 experts. Patients aged more than 3 months and not critically ill were eligible. The SCORE-AI was validated using 3 independent test data sets: a multicenter data set of 100 representative EEGs evaluated by 11 experts, a single-center data set of 9785 EEGs evaluated by 14 experts, and for benchmarking with previously published AI models, a data set of 60 EEGs with external reference standard. No patients who met eligibility criteria were excluded., Main Outcomes and Measures: Diagnostic accuracy, sensitivity, and specificity compared with the experts and the external reference standard of patients' habitual clinical episodes obtained during video-EEG recording., Results: The characteristics of the EEG data sets include development data set (N = 30 493; 14 980 men; median age, 25.3 years [95% CI, 1.3-76.2 years]), multicenter test data set (N = 100; 61 men, median age, 25.8 years [95% CI, 4.1-85.5 years]), single-center test data set (N = 9785; 5168 men; median age, 35.4 years [95% CI, 0.6-87.4 years]), and test data set with external reference standard (N = 60; 27 men; median age, 36 years [95% CI, 3-75 years]). The SCORE-AI achieved high accuracy, with an area under the receiver operating characteristic curve between 0.89 and 0.96 for the different categories of EEG abnormalities, and performance similar to human experts. Benchmarking against 3 previously published AI models was limited to comparing detection of epileptiform abnormalities. The accuracy of SCORE-AI (88.3%; 95% CI, 79.2%-94.9%) was significantly higher than the 3 previously published models (P < .001) and similar to human experts., Conclusions and Relevance: In this study, SCORE-AI achieved human expert level performance in fully automated interpretation of routine EEGs. Application of SCORE-AI may improve diagnosis and patient care in underserved areas and improve efficiency and consistency in specialized epilepsy centers.

Background: Adult spinal deformity (ASD) surgery can improve patient pain and physical function but is associated with high complication rates and long postoperative recovery. Accordingly, if given a choice, patients may indicate they would not undergo ASD surgery again., Purpose: Evaluate surgically treated ASD patients to assess if given the option (1) would surgically treated ASD patients choose to undergo the same ASD surgery again, (2) would the treating surgeon perform the same ASD surgery again and if not why, (3) evaluate for consensus and/or discrepancies between patient and surgeon opinions for willingness to perform/receive the same surgery, and (4) evaluate for associations with willingness to undergo or not undergo the same surgery again and patient demographics, patient reported outcomes, and postoperative complications., Study Design: Retrospective review of a prospective ASD study., Patient Sample: Surgically treated ASD patients enrolled into a multicenter prospective study., Outcome Measures: Scoliosis Research Society-22r questionnaire (SRS-22r), Short Form-36v2 questionnaire (SF-36) physical component summary (PCS) and mental component summary (MCS), Oswestry Disability Index (ODI), numeric pain rating for back pain (NRS back) and leg pain (NRS leg), minimal clinically important difference (MCID) for SRS-22r domains and ODI, intraoperative and postoperative complications, surgeon and patient satisfaction with surgery., Methods: Surgically treated ASD patients prospectively enrolled into a multicenter study were asked at minimum 2-year postoperative, if, based upon their hospital and surgical experiences and surgical recovery experiences, would the patient undergo the same surgery again. Treating surgeons were then matched to their corresponding patients, blinded to the patients' preoperative and postoperative patient reported outcome measures, and interviewed and asked if (1) the surgeon believed that the corresponding patient would undergo the surgery again, (2) if the surgeon believed the corresponding patient was improved by the surgery and (3) if the surgeon would perform the same surgery on the corresponding patient again, and if not why. ASD patients were divided into those indicating they would (YES), would not (NO) or were unsure (UNSURE) if they would have same surgery again. Agreement between patient and surgeon willingness to receive/perform the same surgery was assessed and correlations between patient willingness for same surgery, postoperative complications, spine deformity correction, patient reported outcomes (PROs)., Results: A total of 580 of 961 ASD patients eligible for study were evaluated. YES (n=472) had similar surgical procedures performed, similar duration of hospital and ICU stay, similar spine deformity correction and similar postoperative spinal alignment as NO (n=29; p>.05). UNSURE (n=79) had greater preoperative depression and opioid use rates, UNSURE and NO had more postoperative complications requiring surgery, and UNSURE and NO had fewer percentages of patients reaching postoperative MCID for SRS-22r domains and MCID for ODI than YES (p<.05). Comparison of patient willingness to receive the same surgery versus surgeon perceptions on patient's willingness to receive the same surgery demonstrated surgeons accurately identified YES (91.1%) but poorly identified NO (13.8%; p<.05)., Conclusions: If given a choice, 18.6% of surgically treated ASD patients indicated they were unsure or would not undergo the surgery again. ASD patients indicating they were unsure or would not undergo ASD surgery again had greater preoperative depression, greater preoperative opioid use, worse postoperative PROs, fewer patients reaching MCID, more complications requiring surgery, and greater postoperative opioid use. Additionally, patients that indicated they would not have the same surgery again were poorly identified by their treating surgeons compared to patients indicating they would be willing to receive the same surgery again. More research is needed to understand patient expectations and improve patient experiences following ASD surgery., Competing Interests: Declaration of competing interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Adult spinal deformity (ASD) represents a major cause of disability in the elderly population in the United States. Surgical intervention has been shown to reduce disability and pain in properly indicated patients. However, there is a small subset of patients in whom nonoperative treatment is also able to durably maintain or improve symptoms., Objective: To examine the factors associated with successful nonoperative management in patients with ASD., Methods: We retrospectively evaluated a cohort of 207 patients with nonoperative ASD, stratified into 3 groups: (1) success, (2) no change, and (3) failure. Success was defined as a gain in minimal clinically importance difference in both Oswestry Disability Index and Scoliosis Research Society-Pain. Logistic regression model and conditional inference decision trees established cutoffs for success according to baseline (BL) frailty and sagittal vertical axis., Results: In our cohort, 44.9% of patients experienced successful nonoperative treatment, 22.7% exhibited no change, and 32.4% failed. Successful nonoperative patients at BL were significantly younger, had a lower body mass index, decreased Charlson Comorbidity Index, lower frailty scores, lower rates of hypertension, obesity, depression, and neurological dysfunction (all P < .05) and significantly higher rates of grade 0 deformity for all Schwab modifiers (all P < .05). Conditional inference decision tree analysis determined that patients with a BL ASD-frailty index ≤ 1.579 (odds ratio: 8.3 [4.0-17.5], P < .001) were significantly more likely to achieve nonoperative success., Conclusion: Success of nonoperative treatment was more frequent among younger patients and those with less severe deformity and frailty at BL, with BL frailty the most important determinant factor. The factors presented here may be useful in informing preoperative discussion and clinical decision-making regarding treatment strategies., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

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.

Purpose: Despite adequate correction, the pelvis may fail to readjust, deemed pelvic nonresponse (PNR). To assess alignment outcomes [PNR, proximal junctional kyphosis (PJK), postoperative cervical deformity (CD)] following adult spinal deformity (ASD) surgery utilizing different realignment strategies., Materials and Methods: ASD patients with two-year data were included. PNR defined as undercorrected in age-adjusted pelvic tilt (PT) at six weeks and maintained at two years. Patients classified by alignment utilities: (a) improvement in Scoliosis Research Society-Schwab sagittal vertical axis, (b) matching in age-adjusted pelvic incidence-lumbar lordosis, (c) matching in Roussouly, (d) aligning Global Alignment and Proportionality (GAP) score. Multivariable regression analyses, controlling for age, baseline deformity, and surgical factors, assessed rates of PNR, PJK, and CD development following realignment., Results: A total of 686 patients met the inclusion criteria. Rates of postoperative PJK and CD were not significant in the PNR group (both P >0.15). PNR patients less often met substantial clinical benefit in Oswestry Disability Index by two years [odds ratio: 0.6 (0.4-0.98)]. Patients overcorrected in age-adjusted pelvic incidence-lumbar lordosis, matching Roussouly, or proportioned in GAP at six weeks had lower rates of PNR (all P <0.001). Incremental addition of classifications led to 0% occurrence of PNR, PJK, and CD. Stratifying by baseline PT severity, Low and moderate deformity demonstrated the least incidence of PNR (7.7%) when proportioning in GAP at six weeks, while severe PT benefited most from matching in Roussouly (all P <0.05)., Conclusions: Following ASD corrective surgery, 24.9% of patients showed residual pelvic malalignment. This occurrence was often accompanied by undercorrection of lumbopelvic mismatch and less improvement of pain. However, overcorrection in any strategy incurred higher rates of PJK. We recommend surgeons identify a middle ground using one, or more, of the available classifications to inform correction goals in this regard., Level of Evidence: III., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

To examine the feasibility and safety of blood flow restricted walking (BFR-W) in patients with intermittent claudication (IC). Moreover, to evaluate changes in objective performance-based and self-reported functioning following 12 weeks of BFR-W., Materials and Methods: Sixteen patients with IC were recruited from two departments of vascular surgery. The BFR-W programme implied the application of a pneumatic cuff around the proximal part of the affected limb at 60% limb occlusion pressure in five intervals of 2 min, four times per week for 12 weeks. Feasibility was evaluated by adherence and completion rates of the BFR-W programme. Safety was evaluated by adverse events, ankle-brachial index (ABI) at baseline and follow-up, and pain on a numerical rating scale (NRS pain) before and 2 min after training sessions. Furthermore, changes in performance between baseline and follow-up were evaluated with the 30 seconds sit-to-stand test (30STS), the 6-minute walk test (6MWT) and the IC questionnaire (ICQ)., Results: Fifteen out of 16 patients completed the 12-week BFR-W programme and adherence was 92.8% (95% CI: 83.4; 100%). One adverse event unrelated to the intervention was reported causing one patient to terminate the programme 2 weeks prematurely. Mean NRS pain 2 min following BFR-W was 1.8 (95% CI [1.7-2]). ABI, 30STS, 6MWT and ICQ score were improved at follow-up., Conclusions: BFR-W is feasible and appears to be safe in terms of completion rate, adherence to the training protocol, and adverse events in patients with IC. Further investigation of the effectiveness and safety of BFR-W compared to regular walking exercise is needed., Competing Interests: There are no conflicts of interest., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Design: Diagnostic binary threshold analysis., Objective: (1) Perform a sensitivity analysis demonstrating the test performance metrics for any combination of proximal junctional angle (PJA) magnitude and change; (2) Propose a new proximal junctional kyphosis (PJK) criteria., Summary of Background Data: Previous definitions of PJK have been arbitrarily selected and then tested through retrospective case series, often showing little correlation with clinical outcomes., Materials and Methods: Surgically treated adult spinal deformity patients (≥4 levels fused) enrolled into a prospective, multicenter database were evaluated at a minimum 2-year follow-up for proximal junctional failure (PJF). Using PJF as the outcome of interest, test performance metrics including sensitivity, positive predictive value, and F1 metrics (harmonic mean of precision and recall) were calculated for all combinations of PJA magnitude and change using different combinations of perijunctional vertebrae. The combination with the highest F1 score was selected as the new PJK criteria. Performance metrics of previous PJK definitions and the new PJK definition were compared., Results: Of the total, 669 patients were reviewed. PJF rate was 10%. Overall, the highest F1 scores were achieved when the upper instrumented vertebrae -1 (UIV-1)/UIV+2 angle was measured. For lower thoracic cases, out of all the PJA and magnitude/change combinations tested, a UIV-1/UIV+2 magnitude of -28° and a change of -20° was associated with the highest F1 score. For upper thoracic cases, a UIV-1/UIV+2 magnitude of -30° and a change of -24° were associated with the highest F1 score. Using PJF as the outcome, patients meeting this new criterion (11.5%) at 6 weeks had the lowest survival rate (74.7%) at 2 years postoperative, compared with Glattes (84.4%) and Bridwell (77.4%)., Conclusions: Out of all possible PJA magnitude and change combinations, without stratifying by upper thoracic versus lower thoracic fusions, a magnitude of ≤-28° and a change of ≤-22° provide the best test performance metrics for predicting PJF., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To investigate the variation in total episode-of-care (EOC) payment and quality-adjusted life-year (QALY) gain for complex adult spine deformity surgeries in the United States, adjusting for case type and surgeon preferences., Methods: Patients aged >18 years with adult spine deformity with Medicare Severity-Diagnosis-Related Groups (DRGs) 453-460 and a minimum of 2 years of follow-up from index surgery were included. Index and total payments were calculated using Medicare's Inpatient Prospective Payment System. All costs were adjusted for inflation to 2020 U.S. dollar values. QALYs gained were calculated using baseline, 1-year, and 2-year Short-Form 6D scores. Mixed-effect models were used to estimate the proportion of variation in total EOC payment and QALY gain., Results: A total of 330/543 patients from 6 sites were included. Mean age was 62.4 ± 11.9 years, 79% were women, and 92% were white. The mean index and total EOC payment were $77,302 and $93,182, respectively. Patients gained on average 0.15 QALY (P < 0.0001) 2 years after surgery. In unadjusted analysis, 39% of the variation in total EOC payment across the 6 centers was attributable to relative weight of DRG and base rate. Adjusting for patient and procedural factors increased the proportion of variation in total EOC payments across the centers to 56%. Less than 2% of the variation in QALY gain was observed across the 6 centers., Conclusions: Medicare-based payments for complex spine deformity fusions are primarily driven by relative weight of the DRG and the hospital's base rate. Patient and procedural factors are unaccounted for in the DRG-based payments made to the providers., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Study Design: A retrospective cohort study., Objective: To assess whether patient outcomes and cost-effectiveness of adult spinal deformity (ASD) surgery have improved over the past decade., Background: Surgery for ASD is an effective intervention, but one that is also associated with large initial healthcare expenditures. Changes in the cost profile for ASD surgery over the last decade has not been evaluated previously., Materials and Methods: ASD patients who received surgery between 2008 and 2019 were included. Analysis of covariance was used to establish estimated marginal means for outcome measures [complication rates, reoperations, health-related quality of life, total cost, utility gained, quality adjusted life years (QALYs), cost-efficiency (cost per QALY)] by year of initial surgery. Cost was calculated using the PearlDiver database and represented national averages of Medicare reimbursement for services within a 30-day window including length of stay and death differentiated by complication/comorbidity, revision, and surgical approach. Internal cost data was based on individual patient diagnosis-related group codes, limiting revisions to those within two years (2Y) of the initial surgery. Cost per QALY over the course of 2008-2019 were then calculated., Results: There were 1236 patients included. There was an overall decrease in rates of any complication (0.78 vs . 0.61), any reoperation (0.25 vs . 0.10), and minor complication (0.54 vs . 0.37) between 2009 and 2018 (all P <0.05). National average 2Y cost decreased at an annual rate of $3194 ( R2 =0.6602), 2Y utility gained increased at an annual rate of 0.0041 ( R2 =0.57), 2Y QALYs gained increased annually by 0.008 ( R2 =0.57), and 2Y cost per QALY decreased per year by $39,953 ( R2 =0.6778)., Conclusion: Between 2008 and 2019, rates of complications have decreased concurrently with improvements in patient reported outcomes, resulting in improved cost effectiveness according to national Medicare average and individual patient cost data. The value of ASD surgery has improved substantially over the course of the last decade., Competing Interests: The author reports no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As corrective surgery for cervical deformity (CD) increases, so does the rate of complications and reoperations. To minimize suboptimal postoperative outcomes, it is important to develop a tool that allows for proper preoperative risk stratification., Objective: To develop a prognostic utility for identification of risk factors that lead to the development of major complications and unplanned reoperations., Methods: CD patients age 18 years or older were stratified into 2 groups based on the postoperative occurrence of a revision and/or major complication. Multivariable logistic regressions identified characteristics that were associated with revision or major complication. Decision tree analysis established cutoffs for predictive variables. Models predicting both outcomes were quantified using area under the curve (AUC) and receiver operating curve characteristics., Results: A total of 109 patients with CD were included in this study. By 1 year postoperatively, 26 patients experienced a major complication and 17 patients underwent a revision. Predictive modeling incorporating preoperative and surgical factors identified development of a revision to include upper instrumented vertebrae > C5, lowermost instrumented vertebrae > T7, number of unfused lordotic cervical vertebrae > 1, baseline T1 slope > 25.3°, and number of vertebral levels in maximal kyphosis > 12 (AUC: 0.82). For developing a major complication, a model included a current smoking history, osteoporosis, upper instrumented vertebrae inclination angle < 0° or > 40°, anterior diskectomies > 3, and a posterior Smith Peterson osteotomy (AUC: 0.81)., Conclusion: Revisions were predicted using a predominance of radiographic parameters while the occurrence of major complications relied on baseline bone health, radiographic, and surgical characteristics., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Study Design: Retrospective cohort study., Objective: Assess changes in outcomes and surgical approaches for adult cervical deformity surgery over time., Summary of Background Data: As the population ages and the prevalence of cervical deformity increases, corrective surgery has been increasingly seen as a viable treatment. Dramatic surgical advancements and expansion of knowledge on this procedure have transpired over the years, but the impact on cervical deformity surgery is unknown., Materials and Methods: Adult cervical deformity patients (18 yrs and above) with complete baseline and up to the two-year health-related quality of life and radiographic data were included. Descriptive analysis included demographics, radiographic, and surgical details. Patients were grouped into early (2013-2014) and late (2015-2017) by date of surgery. Univariate and multivariable regression analyses were used to assess differences in surgical, radiographic, and clinical outcomes over time., Results: A total of 119 cervical deformity patients met the inclusion criteria. Early group consisted of 72 patients, and late group consisted of 47. The late group had a higher Charlson Comorbidity Index (1.3 vs. 0.72), more cerebrovascular disease (6% vs. 0%, both P <0.05), and no difference in age, frailty, deformity, or cervical rigidity. Controlling for baseline deformity and age, late group underwent fewer three-column osteotomies [odds ratio (OR)=0.18, 95% confidence interval (CI): 0.06-0.76, P =0.014]. At the last follow-up, late group had less patients with: a moderate/high Ames horizontal modifier (71.7% vs. 88.2%), and overcorrection in pelvic tilt (4.3% vs. 18.1%, both P <0.05). Controlling for baseline deformity, age, levels fused, and three-column osteotomies, late group experienced fewer adverse events (OR=0.15, 95% CI: 0.28-0.8, P =0.03), and neurological complications (OR=0.1, 95% CI: 0.012-0.87, P =0.03)., Conclusion: Despite a population with greater comorbidity and associated risk, outcomes remained consistent between early and later time periods, indicating general improvements in care. The later cohort demonstrated fewer three-column osteotomies, less suboptimal realignments, and concomitant reductions in adverse events and neurological complications. This may suggest a greater facility with less invasive techniques., Competing Interests: International Spine Study Group reports conflicts of interest from NuVasive, and SI Bone. Past conflicts include DePuy Synthes, K2M, Stryker, Biomet, Allosource, and Orthofix. The remaining authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Three-column osteotomies (3COs), usually in the form of pedicle subtraction or vertebral column resection, have become common in adult spinal deformity surgery. Although a powerful tool for deformity correction, 3COs can increase the risks of perioperative morbidity., Methods: Operative patients with adult spinal deformity (Cobb angle of >20°, sagittal vertical axis [SVA] of >5 cm, pelvic tilt of >25°, and/or thoracic kyphosis of >60°) with available baseline and 2-year radiographic and health-related quality-of-life (HRQoL) data were included. Patients were stratified into 2 groups by surgical year: Group I (2008 to 2013) and Group II (2014 to 2018). Patients with 3COs were then isolated for outcomes analysis. Severe sagittal deformity was defined by an SVA of >9.5 cm. Best clinical outcome (BCO) was defined as an Oswestry Disability Index (ODI) of <15 and Scoliosis Research Society (SRS)-22 of >4.5. Multivariable regression analyses were used to assess differences in surgical, radiographic, and clinical parameters., Results: Seven hundred and fifty-two patients with adult spinal deformity met the inclusion criteria, and 138 patients underwent a 3CO. Controlling for baseline SVA, PI-LL (pelvic incidence minus lumbar lordosis), revision status, age, and Charlson Comorbidity Index (CCI), Group II was less likely than Group I to have a 3CO (21% versus 31%; odds ratio [OR] = 0.6; 95% confidence interval [CI] = 0.4 to 0.97) and more likely to have an anterior lumbar interbody fusion (ALIF; OR = 1.6; 95% CI = 1.3 to 2.3) and a lateral lumbar interbody fusion (LLIF; OR = 3.8; 95% CI = 2.3 to 6.2). Adjusted analyses showed that Group II had a higher likelihood of supplemental rod usage (OR = 21.8; 95% CI = 7.8 to 61) and a lower likelihood of proximal junctional failure (PJF; OR = 0.23; 95% CI = 0.07 to 0.76) and overall hardware complications by 2 years (OR = 0.28; 95% CI = 0.1 to 0.8). In an adjusted analysis, Group II had a higher likelihood of titanium rod usage (OR = 2.7; 95% CI = 1.03 to 7.2). Group II had a lower 2-year ODI and higher scores on Short Form (SF)-36 components and SRS-22 total (p < 0.05 for all). Controlling for baseline ODI, Group II was more likely to reach the BCO for the ODI (OR = 2.8; 95% CI = 1.2 to 6.4) and the SRS-22 total score (OR = 4.6; 95% CI = 1.3 to 16)., Conclusions: Over a 10-year period, the rates of 3CO usage declined, including in cases of severe deformity, with an increase in the usage of PJF prophylaxis. A better understanding of the utility of 3CO, along with a greater implementation of preventive measures, has led to a decrease in complications and PJF and a significant improvement in patient-reported outcome measures., Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H179 )., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Frailty is influential in determining operative outcomes, including complications, in patients with cervical deformity (CD)., Objective: To assess whether frailty status limits the highest achievable outcomes of patients with CD., Methods: Adult patients with CD with 2-year (2Y) data included. Frailty stratification: not frail (NF) <0.2, frail (F) 0.2 to 0.4, and severely frail (SF) >0.4. Analysis of covariance established estimated marginal means based on age, invasiveness, and baseline deformity, for improvement, deterioration, or maintenance in Neck Disability Index (NDI), Modified Japanese Orthopaedic Association (mJOA), and Numerical Rating Scale Neck Pain., Results: One hundred twenty-six patients with CD included 29 NF, 83 F, and 14 SF. The NF group had the highest rates of deterioration and lowest rates of improvement in cervical Sagittal Vertical Axis and horizontal gaze modifiers. Two-year improvements in NDI by frailty: NF: -11.2, F: -16.9, and SF: -14.6 ( P = .524). The top quartile of NF patients also had the lowest 1-year (1Y) NDI (7.0) compared with F (11.0) and SF (40.5). Between 1Y and 2Y, 7.9% of patients deteriorated in NDI, 71.1% maintained, and 21.1% improved. Between 1Y and 2Y, SF had the highest rate of improvement (42%), while NF had the highest rate of deterioration (18.5%)., Conclusion: Although frail patients improved more often by 1Y, SF patients achieve most of their clinical improvement between 1 and 2Y. Frailty is associated with factors such as osteoporosis, poor alignment, neurological status, sarcopenia, and other medical comorbidities. Similarly, clinical outcomes can be affected by many factors (fusion status, number of pain generators within treated levels, integrity of soft tissues and bone, and deformity correction). Although accounting for such factors will ultimately determine whether frailty alone is an independent risk factor, these preliminary findings may suggest that frailty status affects the clinical outcomes and improvement after CD surgery., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Ca 2+ /calmodulin-dependent protein kinase II alpha (CaMKIIα) is a multifunctional Ser/Thr kinase involved in several neuronal signaling pathways including synaptic plasticity. CaMKIIα autonomous activity is highly dependent on Thr286 autophosphorylation (pThr286), which is widely used as a readout for its enzymatic activity. To readily characterise compounds and potential drug candidates targeting CaMKIIα, a simple, generic cell-based assay for quantification of pThr286 levels is needed. In this study, we present a cell-based assay using an adapted ELISA as a suitable and higher throughput alternative to Western blotting. In this 96-well plate-based assay, we use whole HEK293T cells recombinantly expressing CaMKIIα and apply a phospho-specific antibody to detect pThr286 levels by chemiluminescence. In parallel, total CaMKIIα expression levels are detected by fluorescence using an Alexa488-conjugated anti-myc antibody targeting a C-terminal myc-tag. By multiplexing chemiluminescence and fluorescence, phosphorylation levels are normalised to CaMKIIα total expression within each well. The specificity of the assay was confirmed using a phosphodead mutant (T286A) of CaMKIIα. By applying Ca 2+ or known CaMKIIα inhibitors (KN93, tatCN21 and AS100105) and obtaining concentration-response curves, we demonstrate high sensitivity and validity of the assay. Lastly, we demonstrate the versatility of the assay by determining autophosphorylation levels in CaMKIIα patient-related mutations, known to possess altered pThr286 responses (E109D, E183V and H282R). The established assay for CaMKIIα is a reproducible, easily implemented, and facile ELISA-based assay that allows for reliable quantification of pThr286 levels., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hand eczema (HE) is frequently associated with Staphylococcus aureus; however, its role in the pathogenesis of HE is poorly understood., Objective: To investigate the temporal variation in S aureus subtypes, ie, clonal complex (CC) types, on the hands and relate it to S aureus colonization in the nose and severity in a cohort of HE patients., Methods: S aureus from the hands and nose of 50 adult HE patients and 50 controls was prospectively identified at 5 visits over 3 weeks., Results: S aureus was identified on the hands of 23 (46%) patients at 2 or more visits and on the hands of 1 control once. Of the HE patients with S aureus colonization, 78% had the same S aureus CC type over time. Twenty-one patients had the same S aureus CC type on the hands and in the nose. Persistent colonization was strongly related to an increased disease severity., Limitations: A relatively small S aureus culture-positive population., Conclusion: The temporal stability of S aureus CC type and high occurrence of the identical subtypes on the hands and in the nose imply that S aureus colonization in patients with HE is of a more permanent nature. Taken together with the finding that persistent colonization and HE severity are clearly related, our results indicate that S aureus may contribute to the perpetuating course of HE., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

The risk of thrombotic events dramatically increases with age and may be accelerated in women by the cessation of endogenous estrogen production at menopause. Patients at risk of thrombosis are prescribed dual anti-platelet therapy (DAPT; aspirin and a P2Y 12 antagonist) and are encouraged to participate in regular physical activity, as these modalities improve nitric oxide and prostacyclin-mediated inhibition of platelet aggregation., Methods: We assessed prostacyclin sensitivity as well as basal platelet reactivity with and without in vitro DAPT before and after an 8-week high-intensity exercise training program in 13 healthy, sedentary postmenopausal women. The training intervention consisted of three 1 h sessions per week. Isolated platelets were analyzed for thromboxane A 2 receptor, thromboxane A 2 synthase, cyclooxygenase-1, and prostacyclin receptor protein expression. Additionally, plasma 6-keto prostaglandin F 1 and thromboxane B α and thromboxane B 2 levels were determined., Results: Exercise training made platelets more sensitive to the inhibitory effects of prostacyclin on thromboxane-, collagen-, and adenosine 5'-diphosphate (ADP)-induced aggregation, as well as thrombin-receptor activator peptide 6- and ADP-induced aggregation with DAPT. However, there was no change in protein expression from isolated platelets or plasma thromboxane B 2 and prostacyclin levels following training., Conclusion: Together, these findings emphasize the importance of promoting physical activity as a tool for reducing thrombotic risk in postmenopausal women and suggest that training status should be considered when prescribing DAPT in this cohort.

Summary of Background Data: The influence of frailty on economic burden following corrective surgery for the adult cervical deformity (CD) is understudied and may provide valuable insights for preoperative planning., Objective: To assess the influence of baseline frailty status on the economic burden of CD surgery., Study Design: Retrospective cohort., Materials and Methods: CD patients with frailty scores and baseline and two-year Neck Disability Index data were included. Frailty score was categorized patients by modified CD frailty index into not frail (NF) and frail (F). Analysis of covariance was used to estimate marginal means adjusting for age, sex, surgical approach, and baseline sacral slope, T1 slope minus cervical lordosis, C2-C7 angle, C2-C7 sagittal vertical axis. Costs were derived from PearlDiver registry data. Reimbursement consisted of a standardized estimate using regression analysis of Medicare payscales for services within a 30-day window including length of stay and death. This data is representative of the national average Medicare cost differentiated by complication/comorbidity outcome, surgical approach, and revision status. Cost per quality-adjusted life-year (QALY) at two years was calculated for NF and F patients., Results: There were 126 patients included. There were 68 NF patients and 58 classified as F. Frailty groups did not differ by overall complications, instance of distal junctional kyphosis, or reoperations (all P >0.05). These groups had similar rates of radiographic and clinical improvement by two years. NF and F had similar overall cost ($36,731.03 vs. $37,356.75, P =0.793), resulting in equivocal costs per QALYs for both patients at two years ($90,113.79 vs. $80,866.66, P =0.097)., Conclusion: F and NF patients experienced similar complication rates and upfront costs, with equivocal utility gained, leading to comparative cost-effectiveness with NF patients based on cost per QALYs at two years. Surgical correction for CD is an economical healthcare investment for F patients when accounting for anticipated utility gained and cost-effectiveness following the procedure., Level of Evidence: III., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Animal and human studies suggest that low concentrations of circulating sex steroid hormones play a critical role in the accelerated loss of muscle mass and strength after menopause. The skeletal muscle can produce sex steroid hormones locally, however, their presence and regulation remain mostly elusive. The purpose of this study was to examine sex steroid hormone concentrations in skeletal muscle biopsies from postmenopausal women before and after 12-weeks of resistance training with (n = 15) or without (n = 16) estrogen therapy, and after acute exercise. Furthermore, associations between circulating sex hormones, intramuscular sex steroid hormones and muscle parameters related to muscle strength, mass and quality were elucidated. Blood and muscle samples, body composition (DXA-scan), muscle size (MR), and muscle strength measures were determined before and after the intervention. An additional blood and muscle sample was collected after the last resistance exercise bout. The results demonstrated reduced intramuscular estradiol, testosterone and dehydroepiandrosterone (DHEA) concentrations after resistance training irrespective of estrogen therapy. Acute exercise had no effect on intramuscular sex hormone levels. Low circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) associated with high muscle mass at baseline, and a decline in circulating FSH after the intervention associated with a greater gain in muscle cross-sectional area in response to the resistance training. In conclusion, intramuscular estradiol, testosterone and DHEA were reduced by resistance training and unaffected by changes in circulating estrogen levels induced by estrogen therapy. Serum FSH and LH were superior predictors of muscle mass compared to other circulating and intramuscular sex steroid hormones., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Among post-COVID-19 symptoms, fatigue is reported as one of the most common, even after mild acute infection, and as the cause of fatigue, myopathy diagnosed by electromyography has been proposed in previous reports. This study aimed to explore the histopathological changes in patients with post-COVID-19 fatigue., Methods: Sixteen patients (mean age = 46 years) with post-COVID-19 complaints of fatigue, myalgia, or weakness persisting for up to 14 months were included. In all patients, quantitative electromyography and muscle biopsies analyzed with light and electron microscopy were taken., Results: Muscle weakness was present in 50% and myopathic electromyography in 75%, and in all patients there were histological changes. Muscle fiber atrophy was found in 38%, and 56% showed indications of fiber regeneration. Mitochondrial changes, comprising loss of cytochrome c oxidase activity, subsarcollemmal accumulation, and/or abnormal cristae, were present in 62%. Inflammation was found in 62%, seen as T lymphocytes and/or muscle fiber human leukocyte antigen ABC expression. In 75%, capillaries were affected, involving basal lamina and cells. In two patients, uncommon amounts of basal lamina were found, not only surrounding muscle fibers but also around nerves and capillaries., Conclusions: The wide variety of histological changes in this study suggests that skeletal muscles may be a major target of SARS-CoV-2, causing muscular post-COVID-19 symptoms. The mitochondrial changes, inflammation, and capillary injury in muscle biopsies can cause fatigue in part due to reduced energy supply. Because most patients had mild-moderate acute affection, the new variants that might cause less severe acute disease could still have the ability to cause long-term myopathy., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Aims: Floorball training induces positive effects on health among untrained older adults. However, the effect of long-term participation (>2 years) in floorball training among elderly males has not been investigated. The aim of the present study was to examine the effect of 5 years of floorball training on risk factors for lifestyle diseases, fitness, physical function, and social capital of elderly males and compare to a control group that continued their usual lifestyle., Methods: Twenty-nine recreationally active elderly men aged 75.1 ± 3.3 (mean ± SD; range: 69-81) years with a height, body mass, and body mass index of 1.78 ± 0.06 m, 79.8 ± 10.9 kg, and 25.8 ± 4.1 kg/m 2 , respectively, volunteered to take part in follow-up investigations about 5 years after participating in a study on the effect of 12 weeks of floorball or petanque training. At the end of the parental study 15 subjects chose to participate in floorball training (floorball group [FG]) whereas 14 subjects (control group [CG]), resumed their usual lifestyle. FG participated in small-sided floorball training 1 h ~1.75 times/week for 5 years in a local sports club., Results: From baseline to 5 years, FG had reduced fat percentage, android, and visceral fat, increased total and leg bone mineral density, leg extension maximal voluntary contraction, maximal walk distance in 6 min and 30 s sit-to-stand repetitions, decreased time for 5 sit-to-stand repetitions and Timed Up and Go ( p  < 0.05). These changes were all different from less favorable changes in CG ( p  < 0.05). In FG there was a decline in maximum oxygen uptake which was smaller than the decline in CG ( p  < 0.05). In addition, FG had developed social capital through the 5 years strengthening their social connectedness and group cohesion., Conclusion: In conclusion, both from a sociological and physiological perspective, small-sided floorball training can be considered a health-promoting activity for older men., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The 70-kDa heat shock protein (HSP70) is a ubiquitous molecular chaperone which is highly inducible by cellular stress such as exercise. To investigate the role of muscle glycogen content on the HSP70 expression, muscle glycogen was manipulated by consumption of either water (H 2 O) or a carbohydrate-enriched diet (CHO) during recovery from 4 h of glycogen-depleting cycling exercise in fourteen elite endurance athletes. Muscle biopsies were obtained pre- and post-exercise, and after 4 and 24 h of recovery, and analyzed for HSP70 mRNA expression, as well as HSP70 protein expression and muscle glycogen within the same skeletal muscle fibers using immunohistochemistry. Exercise reduced glycogen by 59 ± 10% (P < 0.0001). After 4 h of recovery, glycogen approached resting levels in the CHO group (86% of pre, P = 0.28) but remained suppressed in the H 2 O group (41% of pre, P < 0.001) (group × time interaction: P = 0.002). Importantly, both the HSP70 mRNA (+ 1.6-fold (+ 0.28/- 0.24), P = 0.02) and protein expression (+ 147 ± 99%, P < 0.0001) was substantially increased after exercise and remained elevated in both groups after 4 h of recovery, despite clear differences in muscle glycogen content. Thus, muscle glycogen content was not related to the variation in single fiber HSP70 expression at the 4-h time-point (r 2  = 0.004). In conclusion, muscle HSP70 expression remained elevated during recovery from prolonged exercise in highly trained skeletal muscle, irrespective of muscle glycogen availability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Design: 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: 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: 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., Competing Interests: Conflicts of Interest and Source of Funding: All authors report the following disclosures:, (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: Investigate risk factors for PJK including theoretical kyphosis, mechanical loading at the UIV and age adjusted offset alignment., Methods: 373 ASD patients (62.7 yrs ± 9.9; 81%F) with 2-year follow up and UIV of at least L1 and LIV of sacrum were included. Images of patients without PJK, with PJK and with PJF were compared using standard spinopelvic parameters before and after the application of the validated virtual alignment method which corrects for the compensatory mechanisms of PJK. Age-adjusted offset, theoretical thoracic kyphosis and mechanical loading at the UIV were then calculated and compared between groups. A subanalysis was performed based on the location of the UIV (upper thoracic (UT) vs. Lower thoracic (LT))., Results: At 2-years 172 (46.1%) had PJK, and 21 (5.6%) developed PJF. As PJK severity increased, the post-operative global alignment became more posterior secondary to increased over-correction of PT, PI-LL, and SVA (all P < 0.005). Also, a larger under correction of the theoretical TK (flattening) and a smaller bending moment at the UIV (underloading of UIV) was found. Multivariate analysis demonstrated that PI-LL and bending moment offsets from normative values were independent predictors of PJK/PJF in UT group; PT and bending moment difference were independent predictors for LT group., Conclusions: Spinopelvic over correction, under correction of TK (flattening), and under loading of the UIV (decreased bending moment) were associated with PJK and PJF. These differences are often missed when compensation for PJK is not accounted for in post-operative radiographs.

Abstract: Dalgaard, LB, Jørgensen, EB, Oxfeldt, M, Dalgaard, EB, Johansen, FT, Karlsson, M, Ringgaard, S, and Hansen, M. Influence of second generation oral contraceptive use on adaptations to resistance training in young untrained women. J Strength Cond Res 36(7): 1801-1809, 2022-The study purpose was to determine effects of using second generation oral contraceptives (OC) on muscle adaptations to resistance training in young untrained women. Twenty users and 18 nonusers of OC completed a 10-week supervised progressive resistance training program. Before and after the intervention, muscle cross-sectional area (mCSA) of the quadriceps was measured using magnetic resonance imaging and muscle fiber CSA (fCSA) was determined by immunohistochemistry. In addition, body composition (DXA, fat mass/fat-free mass), maximal isometric muscle strength (dynamometry), 5 repetition maximum (5RM) leg press strength, counter movement jump (CMJ) height, and average power using a modified Wingate test were determined. Serum hormone analysis ensured OC compliance and 4-day food records documented dietary intake. After the training period, quadriceps mCSA (OC: 11.0 ± 6.0% vs. non-OC: 9.2 ± 5.0%, p = 0.001), type II fCSA (OC: 19.9 ± 7.9% vs. non-OC: 16.6 ± 7.2%, p = 0.05), muscle strength (knee extension, knee flexion and 5RM, p < 0.001), and functional power (CMJ, AP, p < 0.001) were significantly increased with no significant difference between the groups. However, a tendency toward a greater increase in fat-free mass (FFM) in the OC group was observed (OC: 3.7 ± 3.8% vs. non-OC: 2.7 ± 3.5%, p = 0.08). Collectively, use of second generation OCs in young untrained women did not significantly improve adaptations to 10 weeks of resistance training compared with nonusers. The trend toward greater gains in FFM in the OC group warrant future studies., (Copyright © 2020 National Strength and Conditioning Association.)

Background: 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: 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: 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: 102 surgical CD patients (61 years, 65% F, 30 kg/m 2 ) with BL and 1Y radiographic data were included. 20 patients met definitions for HK and 21 patients met definitions for HL. No differences in demographics or disability were noted. HK had higher estimated blood loss (EBL) with anterior approaches than HL but similar EBL with posterior approach. Operative time did not differ between groups. Control, HL, and HK groups differed in BL TS-CL (36.6° vs. 22.5° vs. 60.7°, P < 0.001) and BL-SVA (10.8 vs. 7.0 vs. -47.8 mm, P = 0.001). HL patients had less discectomies, less corpectomies, and similar osteotomy rates to HK. HL had 3x revisions of HK and controls (28.6 vs. 10.0 vs. 9.2%, respectively, P = 0.046). At 1Y, HL patients had higher cSVA and trended higher SVA and SS than HK. In terms of BL-upper cervical alignment, HK patients had higher McGregor's slope (MGS) (16.1° vs. 3.3°, P = 0.002) and C0-C2 Cobb (43.3° vs. 26.9°, P < 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: Hyperlodotic patients trended higher revision rates with greater radiographic malalignment at 1-year postoperative, perhaps due to undercorrection compared to kyphotic etiologies., Competing Interests: The International Spine Study Group (ISSG) is funded through research grants from DePuy Synthes and supported the current work., (Copyright: © 2022 Journal of Craniovertebral Junction and Spine.)

Objective: The current literature has primarily focused on the 2-year outcomes of operative adult spinal deformity (ASD) treatment. Longer term durability is important given the invasiveness, complications, and costs of these procedures. The aim of this study was to assess minimum 3-year outcomes and complications of ASD surgery., Methods: Operatively treated ASD patients were assessed at baseline, follow-up, and through mailings. Patient-reported outcome measures (PROMs) included scores on the Oswestry Disability Index (ODI), Scoliosis Research Society-22r (SRS-22r) questionnaire, mental component summary (MCS) and physical component summary (PCS) of the SF-36, and numeric rating scale (NRS) for back and leg pain. Complications were classified as perioperative (≤ 90 days), delayed (90 days to 2 years), and long term (≥ 2 years). Analyses focused on patients with minimum 3-year follow-up., Results: Of 569 patients, 427 (75%) with minimum 3-year follow-up (mean ± SD [range] 4.1 ± 1.1 [3.0-9.6] years) had a mean age of 60.8 years and 75% were women. Operative treatment included a posterior approach for 426 patients (99%), with a mean ± SD 12 ± 4 fusion levels. Anterior lumbar interbody fusion was performed in 35 (8%) patients, and 89 (21%) underwent 3-column osteotomy. All PROMs improved significantly from baseline to last follow-up, including scores on ODI (45.4 to 30.5), PCS (31.0 to 38.5), MCS (45.3 to 50.6), SRS-22r total (2.7 to 3.6), SRS-22r activity (2.8 to 3.5), SRS-22r pain (2.3 to 3.4), SRS-22r appearance (2.4 to 3.5), SRS-22r mental (3.4 to 3.7), SRS-22r satisfaction (2.7 to 4.1), NRS for back pain (7.1 to 3.8), and NRS for leg pain (4.8 to 3.0) (all p < 0.001). Degradations in some outcome measures were observed between the 2-year and last follow-up evaluations, but the magnitudes of these degradations were modest and arguably not clinically significant. Overall, 277 (65%) patients had at least 1 complication, including 185 (43%) perioperative, 118 (27%) delayed, and 56 (13%) long term. Notably, the 142 patients who did not achieve 3-year follow-up were similar to the study patients in terms of demographic characteristics, deformities, and baseline PROMs and had similar rates and types of complications., Conclusions: This prospective multicenter analysis demonstrated that operative ASD treatment provided significant improvement of health-related quality of life at minimum 3-year follow-up (mean 4.1 years), suggesting that the benefits of surgery for ASD remain durable at longer follow-up. These findings should prove useful for counseling, cost-effectiveness assessments, and efforts to improve the safety of care.

In 2013, the Danish Health Authorities recommended a change in prophylactic iron supplementation to 40-50 mg/d from gestational week 10. Hence, the aims of the present study were (1) to estimate the prevalence of women who follow the Danish recommendation on iron supplementation during the last 3 weeks of the first trimester of pregnancy and (2) to identify potential sociodemographic, reproductive and health-related pre-pregnancy predictors for iron supplementation during the first trimester. We conducted a cross-sectional study with data from the hospital-based Copenhagen Pregnancy Cohort. Characteristics were analysed by descriptive statistics and multivariable logistic regression analysis was performed to examine the associations between predictors and iron supplementation during the last 3 weeks of the first trimester. The study population consisted of 23 533 pregnant women attending antenatal care at Copenhagen University Hospital - Rigshospitalet from October 2013 to May 2019. The prevalence of iron supplementation according to recommendations was 49⋅1 %. The pre-pregnancy factors of ≥40 years of age, the educational level below a higher degree and a vegetarian or vegan diet were identified as predictors for iron supplementation during the first trimester of pregnancy. Approximately half of the women were supplemented with the recommended dose of iron during the first trimester of pregnancy. We identified pre-pregnancy predictors associated with iron supplementation. Interventions that target women of reproductive age are needed. An enhanced focus on iron supplementation during pregnancy should be incorporated in pre-pregnancy and interpregnancy counselling., (© The Author(s) 2022.)