Mechanisms of lumbar spine "flattening" in adult spinal deformity: defining changes in shape that occur relative to a normative population.

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.

Defining modern iatrogenic flatback syndrome: examination of segmental lordosis in short lumbar fusion patients undergoing thoracolumbar deformity correction.

PURPOSE: Understanding the mechanism and extent of preoperative deformity in revision procedures may provide data to prevent future failures in lumbar spinal fusion patients. METHODS: ASD patients without prior spine surgery (PRIMARY) and with prior short (SHORT) and long (LONG) fusions were included. SHORT patients were stratified into modes of failure: implant, junctional, malalignment, and neurologic. Baseline demographics, spinopelvic alignment, offset from alignment targets, and patient-reported outcome measures (PROMs) were compared across PRIMARY and SHORT cohorts. Segmental lordosis analyses, assessing under-, match, or over-correction to segmental and global lordosis targets, were performed by SRS-Schwab coronal curve type and construct length. RESULTS: Among 785 patients, 430 (55%) were PRIMARY and 355 (45%) were revisions. Revision procedures included 181 (23%) LONG and 174 (22%) SHORT corrections. SHORT modes of failure included 27% implant, 40% junctional, 73% malalignment, and/or 28% neurologic. SHORT patients were older, frailer, and had worse baseline deformity (PT, PI-LL, SVA) and PROMs (NRS, ODI, VR-12, SRS-22) compared to primary patients (p < 0.001). Segmental lordosis analysis identified 93%, 88%, and 62% undercorrected patients at LL, L1-L4, and L4-S1, respectively. SHORT patients more often underwent 3-column osteotomies (30% vs. 12%, p < 0.001) and had higher ISSG Surgical Invasiveness Score (87.8 vs. 78.3, p = 0.006). CONCLUSIONS: Nearly half of adult spinal deformity surgeries were revision fusions. Revision short fusions were associated with sagittal malalignment, often due to undercorrection of segmental lordosis goals, and frequently required more invasive procedures. Further initiatives to optimize alignment in lumbar fusions are needed to avoid costly and invasive deformity corrections. LEVEL OF EVIDENCE: IV: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Distal junctional kyphosis in adult cervical deformity patients: where does it occur?

PURPOSE: To evaluate the impact of the lowest instrumented vertebra (LIV) on Distal Junctional kyphosis (DJK) incidence in adult cervical deformity (ACD) surgery. METHODS: Prospectively collected data from ACD patients undergoing posterior or anterior-posterior reconstruction at 13 US sites was reviewed up to 2-years postoperatively (n = 140). Data was stratified into five groups by level of LIV: C6-C7, T1-T2, T3-Apex, Apex-T10, and T11-L2. DJK was defined as a kyphotic increase > 10° in Cobb angle from LIV to LIV-1. Analysis included DJK-free survival, covariate-controlled cox regression, and DJK incidence at 1-year follow-up. RESULTS: 25/27 cases of DJK developed within 1-year post-op. In patients with a minimum follow-up of 1-year (n = 102), the incidence of DJK by level of LIV was: C6-7 (3/12, 25.00%), T1-T2 (3/29, 10.34%), T3-Apex (7/41, 17.07%), Apex-T10 (8/11, 72.73%), and T11-L2 (4/8, 50.00%) (p < 0.001). DJK incidence was significantly lower in the T1-T2 LIV group (adjusted residual = -2.13), and significantly higher in the Apex-T10 LIV group (adjusted residual = 3.91). In covariate-controlled regression using the T11-L2 LIV group as reference, LIV selected at the T1-T2 level (HR = 0.054, p = 0.008) or T3-Apex level (HR = 0.081, p = 0.010) was associated with significantly lower risk of DJK. However, there was no difference in DJK risk when LIV was selected at the C6-C7 level (HR = 0.239, p = 0.214). CONCLUSION: DJK risk is lower when the LIV is at the upper thoracic segment than the lower cervical segment. DJK incidence is highest with LIV level in the lower thoracic or thoracolumbar junction.

Use of rhBMP-2 for adult spinal deformity surgery: patterns of usage and changes over the past decade.

OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to increase fusion rates; however, cost, limited FDA approval, and possible complications impact its use. Decisions regarding rhBMP-2 use and changes over time have not been well defined. In this study, the authors aimed to assess changes in rhBMP-2 use for adult spinal deformity (ASD) surgery over the past decade. METHODS: A retrospective review of the International Spine Study Group prospective multicenter database was performed to identify ASD patients treated surgically from 2008 to 2018. For assessment of rhBMP-2 use over time, 3 periods were created: 2008-2011, 2012-2015, and 2016-2018. RESULTS: Of the patients identified, 1180 met inclusion criteria, with a mean age 60 years and 30% of patients requiring revision surgery; rhBMP-2 was used in 73.9% of patients overall. The mean rhBMP-2 dose per patient was 23.6 mg. Patients receiving rhBMP-2 were older (61 vs 58 years, p < 0.001) and had more comorbidities (Charlson Comorbidity Index 1.9 vs 1.4, p < 0.001), a higher rate of the Scoliosis Research Society-Schwab pelvic tilt modifier (> 0; 68% vs 62%, p = 0.026), a greater deformity correction (change in pelvic incidence minus lumbar lordosis 15° vs 12°, p = 0.01), and more levels fused (8.9 vs 7.9, p = 0.003). Over the 3 time periods, the overall rate of rhBMP-2 use increased and then stabilized (62.5% vs 79% vs 77%). Stratified analysis showed that after an overall increase in rhBMP-2 use, only patients who were younger than 50 years, those who were smokers, those who received a three-column osteotomy (3CO), and patients who underwent revision sustained an increased rate of rhBMP-2 use between the later two periods. No similar increases were noted for older patients, nonsmokers, primary surgery patients, and patients without a 3CO. The total rhBMP-2 dose decreased over time (26.6 mg vs 24.8 mg vs 20.7 mg, p < 0.001). After matching patients by preoperative alignment, 215 patients were included, and a significantly lower rate of complications leading to revision surgery was observed within the 2012-2015 period compared with the 2008-2011 (21.4% vs 13.0%, p = 0.029) period, while rhBMP-2 was increasingly used (80.5% vs 66.0%, p = 0.001). There was a trend toward a lower rate of pseudarthrosis for patients in the 2012-2015 period, but this difference did not reach statistical significance (7% vs 4.2%, p = 0.283). CONCLUSIONS: The authors found that rhBMP-2 was used in the majority of ASD patients and was more commonly used in those with greater deformity correction. Additionally, over the last 10 years, rhBMP-2 was increasingly used for ASD patients, but the dose has decreased.

Mechanosensitive transcriptional coactivators MRTF-A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape.

Cells of the adult nucleus pulposus (NP) are critically important in maintaining overall disc health and function. NP cells reside in a soft, gelatinous matrix that dehydrates and becomes increasingly fibrotic with age. Such changes result in physical cues of matrix stiffness that may be potent regulators of NP cell phenotype and may contribute to a transition toward a senescent and fibroblastic NP cell with a limited capacity for repair. Here, we investigate the mechanosignaling cues generated from changes in matrix stiffness in directing NP cell phenotype and identify mechanisms that can potentially preserve a biosynthetically active, juvenile NP cell phenotype. Using a laminin-functionalized polyethylene glycol hydrogel, we show that when NP cells form rounded, multicell clusters, they are able to maintain cytosolic localization of myocardin-related transcription factor (MRTF)-A, a coactivator of serum-response factor (SRF), known to promote fibroblast-like behaviors in many cells. Upon preservation of a rounded shape, human NP cells similarly showed cytosolic retention of transcriptional coactivator Yes-associated protein (YAP) and its paralogue PDZ-binding motif (TAZ) with associated decline in activation of its transcription factor TEA domain family member-binding domain (TEAD). When changes in cell shape occur, leading to a more spread, fibrotic morphology associated with stronger F-actin alignment, SRF and TEAD are up-regulated. However, targeted deletion of either cofactor was not sufficient to overcome shape-mediated changes observed in transcriptional activation of SRF or TEAD. Findings show that substrate stiffness-induced promotion of F-actin alignment occurs concomitantly with a flattened, spread morphology, decreased NP marker expression, and reduced biosynthetic activity. This work indicates cell shape is a stronger indicator of SRF and TEAD mechanosignaling pathways than coactivators MRTF-A and YAP/TAZ, respectively, and may play a role in the degeneration-associated loss of NP cellularity and phenotype.-Fearing, B. V., Jing, L., Barcellona, M. N., Witte, S. E., Buchowski, J. M., Zebala, L. P., Kelly, M. P., Luhmann, S., Gupta, M. C., Pathak, A., Setton, L. A. Mechanosensitive transcriptional coactivators MRTF-A and YAP/TAZ regulate nucleus pulposus cell phenotype through cell shape.

Thoracolumbar junction orientation: its impact on thoracic kyphosis and sagittal alignment in both asymptomatic volunteers and symptomatic patients.

PURPOSE: The thoracolumbar junction (TLJ) has not been explored in regard to its contribution to global sagittal alignment. This study aims to define novel sagittal parameters of the TLJ and to assess their roles within global sagittal alignment. METHODS: Included for cross-sectional, retrospective analysis were asymptomatic volunteers and symptomatic patients who had undergone operation for adult spinal deformity. Unique sagittal parameters of the TLJ were measured using the midline of the T12-L1 disk space: The TLJ orientation [TLJO; thoracolumbar tilt (TLT) and slope (TLS)]. Thoracic kyphosis (TK; T5-12), C7-S1 sagittal vertical axis (SVA), lumbar lordosis (LL; L1-S1), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI) were measured. Continuous variables were compared using the independent t test. Pearson correlations examined relationships between the parameters in each group. The asymptomatic TK was calculated using the measurement of the asymptomatic volunteer's TLJO by linear regression. RESULTS: One hundred fifteen asymptomatic volunteers and 127 symptomatic patients were included. Only LL among the lumbopelvic parameters correlated with TK (asymptomatic volunteers: r = - 0.42; symptomatic patients: r = - 0.40). All the pelvic parameters have no direct correlation with TK in both groups. TLJO had stronger correlation with TK [asymptomatic volunteers: r = - 0.68 (TLS), r = 0.41 (TLT); symptomatic patients: r = - 0.56 (TLS), r = 0.44 (TLT)] than the lumbopelvic parameters. TLS correlated with LL (asymptomatic volunteers: r = 0.78; symptomatic patients: r = 0.73). Most pelvic parameters correlated with TLJO except for PI. The asymptomatic TK was estimated by the derived formula: 20.847 + TLS × (- 1.198). CONCLUSION: The TLJO integrates the status of the lumbopelvic sagittal parameters and simultaneously correlates with thoracic and global sagittal alignment. These slides can be retrieved under Electronic Supplementary Material.

Unusual presentation of vertebral endplate Modic changes in congenital scoliosis associated with pain: a report of two cases.

Congenital scoliosis is not normally associated with pain in young children. We are presenting two cases of young patients with congenital scoliosis and moderate to severe pain. There were no spinal cord abnormalities found in these patients. The magnetic resonance imaging and CT scan revealed disc degeneration with Modic changes at the apex of the congenital scoliosis. We hypothesized that the mechanical instability resulting from poor spinal element formations associated with congenital scoliosis was responsible for causing the disc degeneration and endplate changes. Modic changes have been reported to be associated with pain in degenerative conditions of the spine. Both patients underwent a posterior spinal fusion and instrumentation, which relieved their pain immediately.

Analysis of an unexplored group of sagittal deformity patients: low pelvic tilt despite positive sagittal malalignment.

PURPOSE: In adult spinal deformity (ASD), patients increase pelvic tilt (PT) to maintain standing alignment. Previously, ASD patients with low PT and high disability were described. This study investigates this unusual population in terms of demographic, radiographic, and clinical features after three-column osteotomy (3CO). METHODS: In this multicenter retrospective study, ASD patients underwent single lumbar 3CO. Since PT is proportional to pelvic incidence (PI), the low PT group (LowPT) was defined as having a baseline (BL) PT/PI <25th percentile. HRQOL and full spine x-rays were analyzed at BL and 1 year. LowPT patients were compared to those with high PT/PI (HighPT) in a matched range of T1 pelvic angle. RESULTS: LowPT group had PT/PI <0.4 (n = 31). High disability was reported at baseline for both groups with significant improvement postoperatively, but without difference between groups. LowPT had significantly smaller lack lumbar lordosis but larger SVA, T1 spinopelvic inclination. Postoperatively, there were improvements in all sagittal modifiers except PT in LowPT. 33 % of LowPT had an increase in PT (>5°) postoperatively. This subset had more deformity at baseline, achieving good T1SPi postoperative correction but without achieving the SRS-Schwab target SVA at 1 year. CONCLUSION: LowPT group had high levels of disability. After 3CO surgery, low PT patients experience only partial improvements in sagittal vertical axis (SVA) and 33 % of the group increased their PT. Further work is necessary to determine optimal realignment approaches for this unusual set of patients. It is unclear if neuromuscular pathology plays a role in the setting of high SVA without pelvic retroversion.

Complications and intercenter variability of three-column osteotomies for spinal deformity surgery: a retrospective review of 423 patients.

OBJECT: Three-column resection osteotomies (3COs) are commonly performed for sagittal deformity but have high rates of reported complications. Authors of this study aimed to examine the incidence of and intercenter variability in major intraoperative complications (IOCs), major postoperative complications (POCs) up to 6 weeks postsurgery, and overall complications (that is, both IOCs and POCs). They also aimed to investigate the incidence of and intercenter variability in blood loss during 3CO procedures. METHODS: The incidence of IOCs, POCs, and overall complications associated with 3COs were retrospectively determined for the study population and for each of 8 participating surgical centers. The incidence of major blood loss (MBL) over 4 L and the percentage of total blood volume lost were also determined for the study population and each surgical center. Complication rates and blood loss were compared between patients with one and those with two osteotomies, as well as between patients with one thoracic osteotomy (ThO) and those with one lumbar or sacral osteotomy (LSO). Risk factors for developing complications were determined. RESULTS: Retrospective review of prospectively acquired data for 423 consecutive patients who had undergone 3CO at 8 surgical centers was performed. The incidence of major IOCs, POCs, and overall complications was 7%, 39%, and 42%, respectively, for the study population overall. The most common IOC was spinal cord deficit (2.6%) and the most common POC was unplanned return to the operating room (19.4%). Patients with two osteotomies had more POCs (56% vs 38%, p = 0.04) than the patients with one osteotomy. Those with ThO had more IOCs (16% vs 6%, p = 0.03), POCs (58% vs 34%, p < 0.01), and overall complications (67% vs 37%, p < 0.01) than the patients with LSO. There was significant variation in the incidence of IOCs, POCs, and overall complications among the 8 sites (p < 0.01). The incidence of MBL was 24% for the study population, which varied significantly between sites (p < 0.01). Patients with MBL had a higher risk of IOCs, POCs, and overall complications (OR 2.15, 1.76, and 2.01, respectively). The average percentage of total blood volume lost was 55% for the study population, which also varied among sites (p < 0.01). CONCLUSIONS: Given the complexity of 3COs for spinal deformity, it is important for spine surgeons to understand the risk factors and complication rates associated with these procedures. In this study, the overall incidence of major complications following 3CO procedures was 42%. Risks for developing complications included an older age (> 60 years), two osteotomies, ThO, and MBL.

Early-term and mid-term histologic events during single-level posterolateral intertransverse process fusion with rhBMP-2/collagen carrier and a ceramic bulking agent in a nonhuman primate model: implications for bone graft preparation.

STUDY DESIGN: We used a nonhuman primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE: To examine early-term/mid-term descriptive histologic and computerized tomographic events in single-level uninstrumented posterolateral nonhuman primate spinal fusions using rhBMP-2/absorbable collagen sponge (ACS) combined with ceramic bulking agents in 3 different configurations. SUMMARY OF BACKGROUND DATA: rhBMP-2 on an ACS carrier alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in nonhuman primates. METHODS: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite/ß-tricalcium phosphate ceramic bulking agent in 3 formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5 mg/cm (3.0 mg rhBMP-2) was combined with 2.5 cm of ceramic bulking agent per side. Animals were euthanized at 4 and 12 weeks postoperative. Computerized tomography scans were performed immediately postoperatively and every 4 weeks until they were euthanized. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS: Significant histologic differences in the developing fusion appeared between the 3 rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results and previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding and a structure to supporting bone formation of the developing fusion mass.

Revisiting abdominal wall "morbidity" of the extensile anterolateral approach to the thoracolumbar spine.

PURPOSE: To assess patients' perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires. METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ). RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 ± 1.7 years. Average number of anterior fusion levels was 3.5 ± 1.4. Patients achieved high satisfaction rates from surgery (74.5%). AAIQ responses included postoperative pain (33.3%), bulging (41.7%), and limitations in daily activities (18.8%) with only 15.7% experienced moderate-severe pain related to their incisions and only 6.3% seeking treatment for their scars. Post-operatively, 63.2% had a neutral or improved self-image of their torso and trunk, while only 10.2% stating it was much worse. Patients' overall opinion of their scar compared to their normal skin was very positive [average 2.75 ± 2.93 (10 = worst possible scar)]. Favorable scores were also reported for color difference, stiffness, change in thickness, and irregularity in their abdominal scar compared to normal skin. CONCLUSIONS: Following extensile anterolateral approaches to the thoracolumbar spine for ASD, the majority of patients reported mild pain, mild functional limitations, good cosmesis, and high satisfaction rates with their anterior incisions based on validated questionnaires.

Coronal Alignment in Adult Spine Surgery.

Coronal realignment is an important goal in adult spine surgery that has been overshadowed by emphasis on the sagittal plane. As coronal malalignment drives considerable functional disability, a fundamental understanding of its clinical and radiographic evaluation and surgical techniques to prevent its development is of utmost importance. In this study, we review etiologies of coronal malalignment and their radiographic and clinical assessments, risk factors for and functional implications of postoperative coronal malalignment, and surgical strategies to optimize appropriate coronal realignment in adult spine surgery.

Anterior lumbar interbody fusion versus transforaminal lumbar interbody fusion for correction of lumbosacral fractional curves in adult (thoraco)lumbar scoliosis: A systematic review.

Background: Anterior lumbar interbody fusion (ALIF) or transforaminal lumbar interbody fusion (TLIF) may be used to correct the lumbosacral fractional curve (LsFC) in de novo adult (thoraco) lumbar scoliosis. Yet, the relative benefits of ALIF and TLIF for LsFC correction remain largely undetermined. Purpose: To compare the currently available data comparing radiographic correction of the LsFC provided by ALIF and TLIF of LsFC in adult (thoraco)lumbar scoliosis. Methods: A systematic review was performed on original articles discussing fractional curve correction of lumbosacral spinal deformity (using search criteria: "lumbar" and "fractional curve"). Articles which discussed TLIF or ALIF for LsFC correction were presented and radiographic results for TLIF and ALIF were compared. Results: Thirty-one articles were returned in the original search criteria, with 7 articles included in the systematic review criteria. All 7 articles presented radiographic results using TLIF for LsFC correction. Three of these articles also discussed results for patients whose LsFC were treated with ALIFs; 2 articles directly compared TLIF and ALIF for LsFC correction. Level III and level IV evidence indicated ALIF as advantageous for reducing the coronal Cobb angle of the LsFC. There were mixed results on relative efficacy of ALIF and TLIF in the LsFC for restoration of adequate global coronal alignment. Conclusions: Limited level III and IV evidence suggests ALIF as advantageous for reducing the coronal Cobb angle of the LsFC in de novo adult (thoraco) lumbar scoliosis. Relative efficacy of ALIF and TLIF in the LsFC for restoration of global coronal alignment may be dictated by several factors, including directionality and magnitude of preoperative coronal deformity. Given the limited and low-quality evidence, additional research is warranted to determine the ideal interbody support strategies to address the LsFC in adult (thoraco) lumbar scoliosis.

Reply to Tabeling et al. Comment on "Grabala et al. Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study. J. Clin. Med. 2024, 13, 1529".

We are immensely gratified by the considerable interest our study has garnered [...].

Radiological Outcomes of Magnetically Controlled Growing Rods for the Treatment of Children with Various Etiologies of Early-Onset Scoliosis-A Multicenter Study.

Background: The management of spinal deformities diagnosed before the age of 10 is critical due to the child's development, skeletal system, and growth mechanism. Magnetically controlled growing rods (MCGRs) are a surgical treatment option for the growing spine. The aim of this study was to analyze the radiological findings of patients treated with MCGRs for early-onset scoliosis (EOS) of various etiologies. We hypothesized that the MCGRs could provide acceptable long-term radiographic results, such as an increase in the T1-T12 and T1-S1 height and significant overall deformity correction. Methods: We retrospectively reviewed 161 EOS patients with a combined total of 302 MCGRs inserted at five institutions between 2016 and 2022 with a mean follow-up of at least two years. The Cobb angle of the major curve (MC), thoracic kyphosis (TK), lumbar lordosis (LL), and T1-T12 and T1-S1 height measurements were assessed before, after, and during the follow-up. Results: Among the 90 female and 71 male patients, there were 51 neurological, 42 syndromic, 58 idiopathic, and ten congenital scoliosis etiologies. Of the patients, 73 were aged under six years old. The mean follow-up time was 32.8 months. The mean age at placement of the MCGRs was 7 years and that at the last follow-up after fusion surgery was 14.5 years. The mean MC before the initial surgery was 86.2°; following rod implantation, it was 46.9°, and at the last follow-up visit, it was 45.8°. The mean correction rate among the etiology subgroups was from 43% to 50% at follow-up. The mean TK was noted as 47.2° before MCGR implantation, 47.1° after MCGR placement, and 44.5° at the last follow-up visit. The mean T1-T12 height increased by 5.95 mm per year, with a mean T1-S1 height of 10.1 mm per year. Conclusions: MCGR treatment allowed for an average correction of the curvature by 50% during the period of lengthening, while controlling any deformity and growth of the spine, with a significant increase in the T1-T12 and T1-S1 values during the observation period. MCGR treatment in EOS carries a risk of complications. While congenital and syndromic EOS often have short and less flexible curves in those groups of patients, single rods can be as effective and safe. Definitive fusion results in the mean final coronal correction between the start of MCGR treatment and after undergoing PSF of approximately 70%. The mean T1-T12 spinal height increased by 75 mm, while the T1-S1 spinal height gained a mean of 97 mm.

Instrumentation Failure in Adult Spinal Deformity Patients.

In recent years, advances in the surgical treatment of adult spinal deformity (ASD) have led to improved outcomes. Although these advances have helped drive the development of deformity surgery to meet the rising volume of patients seeking surgical treatment, many challenges have yet to be solved. Instrumentation failure remains one of the most common major complications following deformity surgery, associated with significant morbidity due to elevated re-operation rates among those experiencing mechanical complications. The two most frequently encountered subtypes of instrumentation failure are rod fracture (RF) and proximal junctional kyphosis/proximal junctional failure (PJK/PJF). While RF and PJK/PJF are both modes of instrumentation failure, they are two distinct entities with different clinical implications and treatment strategies. Considering that RF and PJK/PJF continue to represent a major challenge for patients with ASD and deformity surgeons alike, this review aims to discuss the incidence, risk factors, clinical impact, treatment strategies, preventive measures, and future research directions for each of these substantial complications.

Severe (>100 Degrees) Thoracic Adolescent Idiopathic Scoliosis - A Comparison of Surgical Approaches.

STUDY DESIGN: Retrospective. OBJECTIVE: Severe curves >100° in adolescent idiopathic scoliosis (AIS) are rare and require careful operative planning. The aim of this study was to assess baseline, perioperative, and 2-year differences between anterior release with posterior instrumentation (AP), posterior instrumentation with posterior column osteotomies (P), and posterior instrumentation with 3-column vertebral osteotomies (VCR). METHODS: Two scoliosis datasets were queried for primary cases of severe thoracic AIS (≥100°) with 2-year follow-up. Pre- and 2-year postoperative radiographic measures (2D and estimated 3D kyphosis), clinical measurements, and SRS-22 outcomes were compared between three approaches. RESULTS: Sixty-one patients were included: 16 AP (26%), 38 P (62%), 7 VCR (11%). Average age was 14.4 ± 2.0 years; 75.4% were female. Preoperative thoracic curve magnitude (AP: 112°, P: 115°, VCR: 126°, P = 0.09) and T5-T12 kyphosis (AP: 38°, P: 59°, VCR: 70°, P = 0.057) were similar between groups. Estimated 3D kyphosis was less in AP vs P (-12° vs 4°, P = 0.016). Main thoracic curves corrected to 36° in AP vs 49° and 48° for P and VCR, respectively (P = 0.02). Change in estimated 3D kyphosis was greater in AP vs P and VCR (34° vs 13°, P = 0.009; 34° vs 7°, P = 0.046). One incomplete spinal cord injury had residual deficits (P; 1/61, 1.6%). All SRS-22 domains improved postoperatively. CONCLUSION: All approaches obtained satisfactory coronal and sagittal correction, but AP had smaller residual coronal deformity and greater kyphosis restoration than the other approaches. This information may help inform the decision of whether to include an anterior release for large thoracic AIS curves.

IGF-1 Peptide Mimetic-functionalized Hydrogels Enhance MSC Survival and Immunomodulatory Activity.

Human mesenchymal stem cells (MSCs) have demonstrated promise when delivered to damaged tissue or tissue defects for their cytokine secretion and inflammation modulation behaviors that can promote repair. Insulin-like growth factor 1 (IGF-1) has been shown to augment MSCs' viability and survival and promote their secretion of cytokines that signal to endogenous cells, in the treatment of myocardial infarction, wound healing, and age-related diseases. Biomaterial cell carriers can be functionalized with growth factor-mimetic peptides to enhance MSC function while promoting cell retention and minimizing off-target effects seen with direct administration of soluble growth factors. Here, we functionalized alginate hydrogels with three distinct IGF-1 peptide mimetics and the integrin-binding peptide, cyclic RGD. One IGF-1 peptide mimetic (IGM-3) was found to activate Akt signaling and support survival of serum-deprived MSCs. MSCs encapsulated in alginate hydrogels that presented both IGM-3 and cRGD showed a significant reduction in pro-inflammatory cytokine secretion when challenged with interleukin-1ß. Finally, MSCs cultured within the cRGD/IGM-3 hydrogels were able to blunt pro-inflammatory gene expression of human primary cells from degenerated intervertebral discs. These studies indicate the potential to leverage cell adhesive and IGF-1 growth factor peptide mimetics together to control therapeutic secretory behavior of MSCs. Significance Statement: Insulin-like growth factor 1 (IGF-1) plays a multifaceted role in stem cell biology and may promote proliferation, survival, migration, and immunomodulation for MSCs. In this study, we functionalized alginate hydrogels with integrin-binding and IGF-1 peptide mimetics to investigate their impact on MSC function. Embedding MSCs in these hydrogels enhanced their ability to reduce inflammatory cytokine production and promote anti-inflammatory gene expression in cells from degenerative human intervertebral discs exposed to proteins secreted by the MSC. This approach suggests a new way to retain and augment MSC functionality using IGF-1 peptide mimetics, offering an alternative to co-delivery of cells and high dose soluble growth factors for tissue repair and immune- system modulation.

Complications and Health-Related Quality of Life in Children with Various Etiologies of Early-Onset Scoliosis Treated with Magnetically Controlled Growing Rods-A Multicenter Study.

Background: Early-onset scoliosis (EOS) refers to spinal deformities that develop and are diagnosed before the age of 10. The most important goals of the surgical treatment of EOS are to stop the progression of curvature, achieve the best possible correction, preserve motion, and facilitate spinal growth. The objectives of this multicenter study were to analyze the risk of complications among patients with EOS treated using magnetically controlled growing rods (MCGRs) and assess the patients' and their parents' quality of life after diagnosis and treatment with a minimum two-year follow-up. Methods: Patients given an ineffective nonoperative treatment qualified for surgery with MCGRs. This study involved 161 patients (90 females and 71 males) who were classified according to the etiology of curvature. The intraoperative and postoperative complications and those that occurred during the continuation of treatment with MCGRs were recorded and analyzed. The 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24) was used to evaluate the patients' quality of life and satisfaction with the treatment. Results: Implant-related complications requiring instrumentation revision were recorded in 26% of the patients. Medical complications occurred in 45% of the population. The EOSQ-24 revealed a significant improvement in the average scores during the follow-up. Conclusions: The treatment of early-onset scoliosis with MCGRs carries 66% risks of incurring medical and mechanical complications, the latter 26% of patients requiring revision procedures. Children with neuromuscular scoliosis, females, and with curvature greater than 90 degrees are at a higher risk of developing complications. Limiting the number of elective surgeries necessitated to prolong the instrumentation and treatment process for patients with MCGRs can greatly enhance their quality of life and satisfaction throughout the follow-up period.

Compensation from mild and severe cases of early proximal junctional kyphosis may manifest as progressive cervical deformity at two year follow-up.

BACKGROUND: Postoperative reciprocal changes (RC) in the cervical spine associated with varying factors of proximal junctional kyphosis (PJK) following fusions of the thoracopelvic spine are poorly understood. PURPOSE: Explore reciprocal changes in the cervical spine associated with varying factors (severity, progression, patient age) of PJK in patients undergoing adult spinal deformity (ASD) correction. PATIENTS AND METHODS: Retrospective review of a multicenter ASD database. INCLUSION: ASD patients > 18 y/o, undergoing fusions from the thoracic spine (UIV: T6-T12) to the pelvis with two-year radiographic data. ASD was defined as: Coronal Cobb angle ≥ 20°, Sagittal Vertical Axis ≥ 5 cm, Pelvic Tilt ≥ 25°, and/or Thoracic Kyphosis ≥ 60°. PJK was defined as a ≥ 10° measure of the sagittal Cobb angle between the inferior endplate of the UIV and the superior endplate of the UIV + 2. Patients were grouped by mild (M; 10°-20°) and severe (S; > 20°) PJK at one year. Propensity Score Matching (PSM) controlled for CCI, age, PI and UIV. Unpaired and paired t test analyses determined difference between RC parameters and change between time points. Pearson bi-variate correlations analyzed associations between RC parameters (T4-T12, TS-CL, cSVA, C2-Slope, and T1-Slope) and PJK descriptors. RESULTS: 284 ASD patients (UIV: T6: 1.1%; T7: 0.7%; T8: 4.6%; T9: 9.9%; T10: 58.8%; T11: 19.4%; T12: 5.6%) were studied. PJK analysis consisted of 182 patients (Mild = 91 and Severe = 91). Significant difference between M and S groups were observed in T4-T12 Δ1Y(- 16.8 v - 22.8, P = 0.001), TS-CLΔ1Y(- 0.6 v 2.8, P = 0.037), cSVAΔ1Y(- 1.8 v 1.9, P = 0.032), and C2 slopeΔ1Y(- 1.6 v 2.3, P = 0.022). By two years post-op, all changes in cervical alignment parameters were similar between mild and severe groups. Correlation between age and cSVAΔ1Y(R = 0.153, P = 0.034) was found. Incidence of severe PJK was found to correlate with TS-CLΔ1Y(R = 0.142, P = 0.049), cSVAΔ1Y(R = 0.171, P = 0.018), C2SΔ1Y(R = 0.148, P = 0.040), and T1SΔ2Y(R = 0.256, P = 0.003). CONCLUSIONS: Compensation within the cervical spine differed between individuals with mild and severe PJK at one year postoperatively. However, similar levels of pathologic change in cervical alignment parameters were seen by two years, highlighting the progression of cervical compensation due to mild PJK over time. These findings provide greater evidence for the development of cervical deformity in individuals presenting with proximal junctional kyphosis.