Mesenchymal Stem Cell Exosomes Enhance Posterolateral Spinal Fusion in a Rat Model.

Spinal fusion, a common surgery performed for degenerative lumbar conditions, often uses recombinant human bone morphogenetic protein 2 (rhBMP-2) that is associated with adverse effects. Mesenchymal stromal/stem cells (MSCs) and their extracellular vesicles (EVs), particularly exosomes, have demonstrated efficacy in bone and cartilage repair. However, the efficacy of MSC exosomes in spinal fusion remains to be ascertained. This study investigates the fusion efficacy of MSC exosomes delivered via an absorbable collagen sponge packed in a poly Ɛ-caprolactone tricalcium phosphate (PCL-TCP) scaffold in a rat posterolateral spinal fusion model. Herein, it is shown that a single implantation of exosome-supplemented collagen sponge packed in PCL-TCP scaffold enhanced spinal fusion and improved mechanical stability by inducing bone formation and bridging between the transverse processes, as evidenced by significant improvements in fusion score and rate, bone structural parameters, histology, stiffness, and range of motion. This study demonstrates for the first time that MSC exosomes promote bone formation to enhance spinal fusion and mechanical stability in a rat model, supporting its translational potential for application in spinal fusion.

Clinical Decision Support System Used in Spinal Disorders: Scoping Review.

BACKGROUND: Spinal disorders are highly prevalent worldwide with high socioeconomic costs. This cost is associated with the demand for treatment and productivity loss, prompting the exploration of technologies to improve patient outcomes. Clinical decision support systems (CDSSs) are computerized systems that are increasingly used to facilitate safe and efficient health care. Their applications range in depth and can be found across health care specialties. OBJECTIVE: This scoping review aims to explore the use of CDSSs in patients with spinal disorders. METHODS: We used the Joanna Briggs Institute methodological guidance for this scoping review and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. Databases, including PubMed, Embase, Cochrane, CINAHL, Web of Science, Scopus, ProQuest, and PsycINFO, were searched from inception until October 11, 2022. The included studies examined the use of digitalized CDSSs in patients with spinal disorders. RESULTS: A total of 4 major CDSS functions were identified from 31 studies: preventing unnecessary imaging (n=8, 26%), aiding diagnosis (n=6, 19%), aiding prognosis (n=11, 35%), and recommending treatment options (n=6, 20%). Most studies used the knowledge-based system. Logistic regression was the most commonly used method, followed by decision tree algorithms. The use of CDSSs to aid in the management of spinal disorders was generally accepted over the threat to physicians' clinical decision-making autonomy. CONCLUSIONS: Although the effectiveness was frequently evaluated by examining the agreement between the decisions made by the CDSSs and the health care providers, comparing the CDSS recommendations with actual clinical outcomes would be preferable. In addition, future studies on CDSS development should focus on system integration, considering end user's needs and preferences, and external validation and impact studies to assess effectiveness and generalizability. TRIAL REGISTRATION: OSF Registries osf.io/dyz3f; https://osf.io/dyz3f.

Increased matrix metalloproteinase-2 in ligamentum flavum hypertrophy and the regulation of MMP-2/TIMPs by elastin-derived peptides.

The study aimed to examine matrix metalloproteinase-2 (MMP-2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin-derived peptides (EDPs) on MMP-2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6- and 12-weeks postsurgery for histological staining, immunohistochemical staining, RT-qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP-2, TIMP-1, and TIMP-2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP-2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP-2 and TIMP-3 levels. EDPs were found to suppress MMP-2 expression and reduce TIMP-1 and TIMP-2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP-2/TIMP-1 and MMP-2/TIMP-2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP-2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP-2/TIMPs ratio in LF cells in an ERC-dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

Characteristics of Spinal Morphology According to the Global Alignment and Proportion (GAP) Score in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study.

STUDY DESIGN: Multi-Ethnic Alignment Normative Study (MEANS) cohort: prospective, cross-sectional, multicenter. OBJECTIVE: To analyze the distribution of GAP scores in the MEANS cohort and compare the spinal shape via stratification by GAP alignment category, age, and country. SUMMARY OF BACKGROUND DATA: The GAP score has been used to categorize spinal morphology and prognosticate adult spinal deformity surgical outcomes and mechanical complications. We analyzed a large, multiethnic, asymptomatic cohort to assess the distribution of GAP scores. METHODS: Four hundred sixty-seven healthy volunteers without spinal disorders were recruited in five countries. Sagittal radiographic parameters were measured via the EOS imaging system. The GAP total and constituent factor scores were calculated for each patient. Kruskal-Wallis rank sum test was performed to compare variables across groups, followed by the post hoc Games-Howell test. Fisher exact test was used to compare categorical variables. The significance level was set to P <0.05. RESULTS: In the MEANS cohort, 13.7% (64/467) of volunteers were ≥60 years old, and 86.3% (403/467) were <60 years old. 76.9% (359/467) was proportioned, 19.5% (91/467) was moderately disproportioned, and 3.6% (17/467) was severely disproportioned. There was no significant difference in the frequency of proportioned, moderately, or severely disproportioned GAP between subjects from different countries ( P =0.060). Those with severely disproportioned GAP alignment were on average 14.5 years older ( P =0.016), had 23.1° lower magnitude lumbar lordosis (LL) ( P <0.001), 14.2° higher pelvic tilt ( P <0.001), 13.3° lower sacral slope ( P <0.001), and 24.1° higher pelvic-incidence (PI)-LL mismatch ( P <0.001), 18.2° higher global tilt ( P <0.001) than those with proportioned GAP; thoracic kyphosis and PI were not significantly different ( P >0.05). CONCLUSIONS: The GAP system applies to a large, multiethnic, asymptomatic cohort. Spinal alignment should be considered on a spectrum, as 19.5% of the asymptomatic volunteers were classified as moderately disproportioned and 3.6% severely disproportioned. Radiographic malalignment does not always indicate symptoms or pathology. LEVEL OF EVIDENCE: 3.

Characteristics of Spinal Morphology According to the "Current" and "Theoretical" Roussouly Classification Systems in a Diverse, Asymptomatic Cohort: Multi-Ethnic Alignment Normative Study (MEANS).

STUDY DESIGN: Cross-sectional cohort study. OBJECTIVE: To classify spinal morphology using the "current" and "theoretical" Roussouly systems and assess sagittal alignment in an asymptomatic cohort. METHODS: 467 asymptomatic volunteers were recruited from 5 countries. Radiographic parameters were measured via the EOS imaging system. "Current" and "theoretical" Roussouly classification was assigned with sagittal whole spine imaging using sacral slope (SS), pelvic incidence (PI), and the lumbar apex. One-way analysis of variance (ANOVA) was performed to compare subject characteristics across Roussouly types, followed by post hoc Bonferroni correction. RESULTS: Volunteers were categorized into 4 groups (Types 1-4) and 1 subgroup (Type 3 AP) using the "current" and "theoretical" Roussouly systems. The mean PI in "current" Roussouly groups was 40.8° (Type 1), 43.6° (Type 2), 52.4° (Type 3), 62.4° (Type 4), and 43.7° (Type 3AP). The mean PI in "theoretical" Roussouly groups was 36.5° (Type 1), 39.1°(Type 2), 52.5° (Type 3), 67.3° (Type 4), and 51.0° (Type 3AP). The difference in PI between "current" and "theoretical" Roussouly types was significant for Type 1 (P = .02), Type 2 (P < .001), Type 4 (P < .001), and Type 3AP (P < .001). 34.7% of subjects had a "current" Roussouly type different from the "theoretical" type. Type 3 theoretical shape had the most frequent mismatch, constituting 61.1% of the mismatched subjects. 51.5% of mismatched Type 3 become "current" Type 4. CONCLUSION: The distribution of Roussouly types differs depending on whether the "current" or "theoretical" classification are employed. A sizeable proportion of volunteers exhibited current and theoretical type mismatch, highlighting the need to interpret sagittal alignment cautiously when utilizing the Roussouly system.

Full-endoscopic versus microscopic spinal decompression for lumbar spinal stenosis: a systematic review & meta-analysis.

BACKGROUND CONTEXT: Symptomatic lumbar spinal stenosis is routinely treated with spinal decompression surgery, with an increasing trend towards minimally invasive techniques. Endoscopic decompression has emerged as a technique which minimizes approach-related morbidity while achieving similar clinical outcomes to conventional open or microscopic approaches. PURPOSE: To assess the safety and efficacy of endoscopic versus microscopic decompression for treatment of lumbar spinal stenosis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A systematic review on randomized and nonrandomized studies comparing endoscopic versus microscopic decompression was conducted, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Treatment effects were computed using pairwise random-effects meta-analysis. Risk of bias was assessed using the Cochrane Risk-of-bias and ROBINS-I tools for randomized and nonrandomized trials respectively. Quality of the overall body of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A total of 19 primary references comprising 1,997 patients and 2,132 spinal levels were included. Endoscopic decompression was associated with significantly reduced intraoperative blood-loss (weighted mean differences [WMD]=-33.29 mL, 95% CI:-51.80 to -14.78, p=.0032), shorter duration of hospital stay (WMD=-1.79 days, 95% CI: -2.63 to 0.95, p=.001), rates of incidental durotomy (RR = 0.63, 95% CI: 0.43 to 0.91, p=.0184) and surgical site infections (RR=0.23, 95% CI: 0.10 to-0.51, p=.001), and a nonsignificant trend towards less back pain, leg pain, and better functional outcomes compared to its microscopic counterpart up to 2-year follow up. CONCLUSIONS: Endoscopic and microscopic decompression are safe and effective techniques for treatment of symptomatic lumbar spinal stenosis. Prospective studies of larger power considering medium to long-term outcomes and rates of iatrogenic instability are warranted to compare potential alignment changes and destabilization from either techniques.

A Comparison between Structural Allografts and Polyetheretherketone Interbody Spacers Used in Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-analysis.

Among interbody implants used during anterior cervical discectomy and fusion (ACDF), structural allografts and polyetheretherketone (PEEK) are the most used spacers. Currently, no consensus has been established regarding the superiority of either implant, with US surgeons preferring structural allografts, whereas UK surgeons preferring PEEK. The purpose of this systematic review (level of evidence, 4) was to compare postoperative and patient-reported outcomes between the use of structural allografts PEEK interbody spacers during ACDF. Five electronic databases (PubMed, Embase, Scopus, Web of Science, and Cochrane) were searched for articles comparing the usage of structural allograft and PEEK interbody spacers during ACDF procedures from inception to April 10, 2023. The searches were conducted using the keywords "Spine," "Allograft," and "PEEK" and were performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Subsequent quality and sensitivity analyses were performed on the included studies. Nine studies involving 1,074 patients were included. Compared with the PEEK group, the structural allograft group had comparable rates of postoperative pseudoarthrosis (p=0.58). However, when stratified according to the number of levels treated, the 3-level ACDF PEEK group was 3.45 times more likely to have postoperative pseudoarthrosis than the structural allograft group (p=0.01). Subsequent postoperative outcomes (rate of subsidence and change in the preoperative and postoperative segmental disc heights) were comparable between the PEEK and structural allograft groups. Patient-reported outcomes (Visual Analog Scale [VAS] of neck pain and Neck Disability Index [NDI]) were comparable. This study showed that for 3-level ACDFs, the use of structural allografts may confer higher fusion rates. However, VAS neck pain, NDI, and subsidence rates were comparable between structural allografts and PEEK cages. In addition, no significant difference in pseudoarthrosis rates was found between PEEK cages and structural allografts in patients undergoing 1- and 2-level ACDFs.

The Importance of Pelvic Obliquity in Assessing Spinal Coronal Alignment: Normative Values, Demographic, and Radiographic Correlations.

STUDY DESIGN: Prospective, cross-sectional study. OBJECTIVE: In a geographically diverse population of asymptomatic volunteers, we sought to report the incidence of pelvic obliquity (PO), establish normative values of PO across patient factors, and assess the correlation of PO with radiographic parameters. SUMMARY OF BACKGROUND DATA: PO is defined as the misalignment of the pelvis and can be assessed through several anatomic landmarks. Significant PO, whether caused by leg-length discrepancy or not, can lead to coronal malalignment which causes severe pain and disability. Significant emphasis has been placed on achieving appropriate sagittal alignment in recent decades; however, a greater understanding of coronal alignment is needed, and PO is a crucial aspect of evaluating the coronal plane in adult spinal deformity patients. METHODS: Asymptomatic adult volunteers, ages 18-80 years, enrolled patients from 5 countries (France, Japan, Singapore, Tunisia, and the United States) in the "multiethnic alignment normative study" cohort (IRB 201812144). The included volunteers had no known spinal disorder(s), no significant neck or back pain (Visual Analog Scale: ≤2; Oswestry Disability Index: ≤20), and no abnormal alignment (Cobb ≤20°). PO was measured in the frontal plane as the distance between the highest points of each acetabulum, calculated along the vertical axis in millimeters (mm). The incidence of PO was defined as PO ≥10 mm. Kruskal-Wallis, Wilcoxon rank-sum, Pearson correlation, and linear regression were used. RESULTS: A total of 467 patients were included, and PO values by age, sex, body mass index, and country were provided. The overall incidence of PO ≥10 mm was 4.3%, and a nonsignificant trend toward increased PO with age was seen ( P = 0.077). No significant differences were seen in PO between sex, ethnicity, or body mass index groups. No significant correlation existed between PO and other commonly used coronal radiographic measurements. CONCLUSION: PO ≥10 mm occurred in 4.3% of asymptomatic volunteers. Despite the importance of recognizing PO in preventing coronal malalignment, PO did not seem to be associated with other radiographic and demographic information, which underscores the importance of intentionally assessing for any PO before surgery. These results in an asymptomatic population provide a foundation for studying PO in patients with spinal pathology.

Changes in Spinopelvic Parameters Between Standing and Sitting Postures: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To report the ratio-of-differences between standing and sitting. To understand how sex and age influence these differences. SUMMARY OF BACKGROUND DATA: Currently, spinal deformity surgery aims to realign the sagittal profile of the spine with-reference-to the standing posture resulting in overcorrection. New studies report significant disparities between standing and sitting spinal alignment. METHODS: A comprehensive search and review of the published literature was performed on 4 platforms in accordance with the PRISMA 2009 checklist by 2 authors independently. RESULTS: From 753 abstracts extracted from the databases, 38 papers involving 5423 patients were identified. sagittal vertical axis was more positive in sitting, with a pooled mean difference of 29.5 mm (95% CI: 17.9-41.0). Pelvic tilt (PT) was larger in sitting, with a pooled mean difference of 16.7 degrees (95% CI: 12.5-20.9), and a pooled odds ratio of 1.2(95% CI:1.1-1.3. P =0.001). Sacral Slope (SS) was smaller and lumbar lordosis (LL) was less lordotic in sitting, with a pooled mean difference of 15.0 degrees (95% CI: 11.918.1) and 21.1 degrees (95% CI:14.5-27.8), respectively, and a pooled odds ratio of 0.7 (95% CI: 0.6-0.8. P <0.001) and 0.7 (95% CI:0.6-0.7, P <0.001), respectively. Pelvic incidence and thoracic kyphosis was similar in sitting. Subgroup meta-analysis comparing odd ratio of standing to sitting showed: Among younger patients (age younger than 50), the PT and LL pooled odds-ratios were 1.4 and 0.7, respectively. Among older patients (age older than or equal to 50), the PT and LL pooled odds-ratios were 1.1 and 0.8, respectively. Among female patients, the SS pooled odds ratio was 0.6. Among male patients, the SS pooled odds ratio was 0.7. CONCLUSION: When comparing sitting to standing, it gives a more positive sagittal vertical axis, a smaller SS and LL, and a larger PT. pelvic incidence and thoracic kyphosis remained similar. Younger and female patients have pronounced differences in SS, PT, and LL, suggesting the existence of age and sex variations, and its role to be considered when planning for spinal realignment surgeries. Clinical outcome studies are required to ascertain the impact of these findings.

Effectiveness of anthocyanin-rich foods on bone remodeling biomarkers of middle-aged and older adults at risk of osteoporosis: a systematic review, meta-analysis, and meta-regression.

CONTEXT: Current osteoporosis pharmacological treatment has undesirable side effects. There is increasing focus on naturally derived food substances that contain phytonutrients with antioxidant effects in promoting health and regulating immune response. OBJECTIVE: This review aims to systematically evaluate the effectiveness of anthocyanin-rich foods on bone remodeling biomarkers in middle-aged and older adults (≥40 y old) at risk of osteoporosis. DATA SOURCES: Randomized controlled trials were searched on 8 bibliographic databases of PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Food Science and Technology Abstracts, Cochrane Library, and ProQuest. DATA EXTRACTION AND ANALYSIS: Thirteen studies were included in the meta-analysis. Receptor activator of nuclear factor kappa-B ligand (RANKL) is exhibited from osteoblastic cells that gathered osteoclasts to bone sites for bone resorption, accelerating bone loss. Anthocyanin-rich food consumption showed statistically nonsignificant effects, with no substantial heterogeneity on bone remodeling biomarkers. However, there was a significant increase in lumbar spine L1-L4 bone mineral density. Mild-to-small effects were seen to largely favor the consumption of anthocyanin-rich foods. Berries (d = -0.44) have a larger effect size of RANKL than plums (d = 0.18), with statistically significant subgroup differences. Random-effects meta-regression found body mass index, total attrition rate, total energy, and dietary carbohydrate and fat intake were significant covariates for the effect size of RANKL. All outcomes had low certainty of evidence. CONCLUSION: Anthocyanin-rich foods may improve bone health in middle-aged and older adults at risk of osteoporosis. This review contributes to the growing interest in nutrient-rich foods as a low-cost and modifiable alternative to promote human health and reduce disease burden. Future high-quality studies with larger sample sizes and longer treatment durations are required to fully understand the effect of anthocyanin-rich foods on bone health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022367136.

Outcomes and Complications of Surgery for Symptomatic Spinal Metastases; a Comparison Between Patients Aged ≥ 70 and <70.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Physicians may be deterred from operating on elderly patients due to fears of poorer outcomes and complications. We aimed to compare the outcomes of surgical treatment of spinal metastases patients aged ≥70-yrs and <70-yrs. MATERIALS AND METHODS: This is a retrospective study of patients surgically treated for metastatic epidural spinal cord compression and spinal instability between January-2005 to December-2021. Follow-up was till death or minimum 1-year post-surgery. Outcomes included post-operative neurological status, ambulatory status, medical and surgical complications. Two Sample t-test/Mann Whitney U test were used for numerical variables and Pearson Chi-Squared or Fishers Exact test for categorical variables. Survival was presented with a Kaplan-Meier curve. P < .05 was significant. RESULTS: We identified 412 patients of which 29 (7.1%) patients were excluded due to loss to follow-up and previous surgical treatment. 79 (20.6%) were ≥70-yrs. Age ≥70-yrs patients had poorer ECOG scores (P = .0017) and Charlson Comorbidity Index (P < .001). No significant difference in modified Tokuhashi score (P = .393) was observed with significantly more ≥ prostate (P < .001) and liver (P = .029) cancer in ≥70-yrs. Improved or maintained normal neurological function (P = .934), independent ambulatory status (P = .171), and survival at 6 months (P = .119) and 12 months (P = .659) was not significantly different between both groups. Medical (P = .528) or surgical (P = .466) complication rates and readmission rates (P = .800) were similar. CONCLUSION: ≥70-yrs patients have comparable outcomes to <70-yr old patients with no significant increase in complication rates. Age should not be a determining factor in deciding surgical management of spinal metastases.

The Posterior Cranial Vertical Line: A Novel Radiographic Marker for Classifying Global Sagittal Alignment.

OBJECTIVE: To define a novel radiographic measurement, the posterior cranial vertical line (PCVL), in an asymptomatic adult population to better understand global sagittal alignment. METHODS: We performed a multicenter retrospective review of prospectively collected radiographic data on asymptomatic volunteers aged 20-79. The PCVL is a vertical plumb line drawn from the posterior-most aspect of the occiput. The horizontal distances of the PCVL to the thoracic apex (TA), posterior sagittal vertical line (PSVL, posterosuperior endplate of S1), femoral head center, and tibial plafond were measured. Classification was either grade 1 (PCVL posterior to TA and PSVL), grade 2 (PCVL anterior to TA and posterior to PSVL), or grade 3 (PCVL anterior to TA and PSVL). RESULTS: Three hundred thirty-four asymptomatic patients were evaluated with a mean age of 41 years. Eighty-three percent of subjects were PCVL grade 1, 15% were grade 2, and 3% were grade 3. Increasing PCVL grade was associated with increased age (p < 0.001), C7-S1 sagittal vertical axis (SVA) (p < 0.001), C2-7 SVA (p < 0.001). Additionally, it was associated with decreased SS (p = 0.045), increased PT (p < 0.001), and increased knee flexion (p < 0.001). CONCLUSION: The PCVL is a radiographic marker of global sagittal alignment that is simple to implement and interpret. Increasing PCVL grade was significantly associated with expected changes and compensatory mechanisms in the aging population. Most importantly, it incorporates cervical alignment parameters such as C2-7 SVA. The PCVL defines global sagittal alignment in adult volunteers and naturally distributes into 3 grades, with only 3% being grade 3 where the PCVL lies anterior to the TA and PSVL.

Multilevel Cervical Disk Arthroplasty: Moving Beyond Two Levels.

Cervical disk arthroplasty (CDA) is well-studied for 1-level and 2-level cervical pathology. There is an increasing trend towards its utilization for greater than 2-level disease as an alternative to the gold standard, anterior cervical discectomy and fusion (ACDF). The number of high-level, prospective studies or randomized trials regarding multilevel CDA is limited but continues to grow as the procedure gains popularity. In appropriately indicated patients with multilevel disease caused by disk herniations or spondylosis without extensive facet arthropathy, CDA shows promising results. Multilevel CDA should be avoided in patients with prior spinal trauma, significant degenerative spondylolisthesis with translation, arthrodesis without mobility, severely incompetent facet joints, ossification of the posterior longitudinal ligament, or kyphotic deformity. With overall similar risk profiles to ACDF but lower theoretical rates of pseudarthrosis and adjacent segment disease, multilevel CDA has been shown to preserve, or perhaps even increase, preoperative cervical range of motion. There are negligible differences in postoperative neck and arm pain, VAS scores, modified Japanese Orthopaedic Association scores, and Neck Disability Index scores when comparing multilevel CDA and ACDF. Despite current indications for multilevel CDA largely being based on single and 2-level data, careful patient selection is critical. Expansion of indications can be expected as literature continues to emerge regarding outcomes and complications in multilevel CDA, as well as with improvements in prosthesis design.

The Thoracolumbar Inflection Point in a Population of Asymptomatic Volunteers: A Multi-Ethnic Alignment Normative Study Cohort Study.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: To show population variance in the Inflection Point (IP) and its role in defining maximum Thoracic Kyphosis (TK) and Lumbar Lordosis (LL). METHODS: 468 asymptomatic adult volunteers were included in the Multi-Ethnic Normative Alignment Study (MEANS). To find parameters correlating with IP, the vertebrae and discs were numbered such that C7 was 0, T1 was 1, with T1-T2 disc being 1.5, etc. Statistical analysis was performed by a correlation matrix for IP and the 9 other selected parameters along with linear regressions. RESULTS: The overall mean IP was 12.44 approximately corresponding to T12-L1 disc with the median being 12.50, range was T8-L4. The cohort was then stratified by sex and ethnicity, but there was no significant difference in IP between groups. IP in younger subjects was 13 (L1), compared to 12.5 (T12-L1 disc) in older subjects (P < .05). IP was moderately correlated with the TK apex (r = .66). No strong correlation was found between IP and LL magnitude or apex, TK magnitude, sacral slope, or Pelvic Incidence (PI). In terms of other sagittal parameters, PI and LL demonstrated a significant positive correlation. PI and TK did not have a strong association. CONCLUSIONS: The mean IP was at the T12-L1 disc, however IP ranged from T8 to L4. Older subjects tended to have a relatively more cephalad IP. No radiographic variable was found to be a strong predictor of the IP. TK apex was found to have a moderate correlation.

Morphological description of sagittal lumbar spinal alignment using curve magnitude, span, and apex-the multiethnic alignment normative study (MEANS).

BACKGROUND CONTEXT: Current definition of lumbar lordosis uses the L1-S1 angle. Prevailing classification of sagittal spinal morphology, derived from a young adult population, classifies the spine into four subtypes defined by their sacral slope (SS) and curve morphology. PURPOSE: To describe physiological sagittal alignment of the lumbar spine across age groups using three main parameters that dictate the lumbar curve: angular magnitude, span, and apex. STUDY DESIGN: A large, multicenter, cross-sectional radiographic comparison study. PATIENT SAMPLE: Four hundred sixty-eight healthy, asymptomatic subjects aged 18 to 80 years from five countries (184 males, 284 females; 98 France, 119 Japan, 79 Singapore, 80 Tunisia, 92 USA, mean age 40.61±14.99 years). OUTCOME MEASURES: Sagittal lumbar profile subtypes clustered based on lumbar curve angular magnitude (ie, Cobb angle of the lumbar lordosis), span, and apex, and described by sagittal radiographic parameters. METHODS: Subjects underwent whole-body low-dose EOS stereoradiographs. Comparisons between conventional L1-S1 lumbar lordosis (cLL) and true lumbar lordosis (tLL, defined by the inflection-S1 angle) were conducted. Using the K-means clustering algorithm, lumbar curve angular magnitude, span and apex were used to classify sagittal spinal morphology into subtypes, stratified across age groups. Further univariate and multivariate analyses were conducted to compare radiographic parameters across subtypes, and identify predictors for the lumbar curve's angular magnitude, span and apex. RESULTS: Mean cLL was -57.27±11.37°, and tLL was -62.62±10.76°. Using tLL, instead of cLL, to describe sagittal spinal morphology, we found significant differences in terms of angular magnitude of the lumbar curve, the median thoracolumbar inflection vertebral level and pelvic incidence-lumbar lordosis mismatch Multivariate analysis found a larger SS, more positive T9 tilt, and more kyphotic T4-T12 predictive for a more lordotic tLL, while a larger overhang distance predicted for a less lordotic tLL (p-values<.001). In addition, a larger T9 tilt, less lordotic L1-L5 and smaller PT were predictors of a more caudal thoracolumbar inflection and lumbar apical vertebral levels (p-values<.001). Sagittal lumbar profiles of subjects age<30 years, 30≤age<60 years and age≥60 years, could be classified into 4, 6, and 3 subtypes, respectively. CONCLUSIONS: Sagittal lumbar profile subtypes vary across age groups, with more homogenous morphologies at the extremes of ages. Improved understanding of the morphological evolution of sagittal spinal profiles with age in asymptomatic individuals will help guide future individualized surgical treatment.

Sagittal spinal alignment varies with an individual's race: results of the multi-ethnic alignment normative study (MEANS).

PURPOSE: Assess normative values of sagittal spinal and lower extremity alignment in asymptomatic volunteers of three difference races. METHODS: Asymptomatic volunteers between the ages of 18-80 years were enrolled prospectively and then analyzed retrospectively from six different centers. Volunteers included reported no significant neck or back pain, nor any known spinal disorder(s). All volunteers underwent a standing full-body or full-spine low dose stereoradiograph. Volunteers were grouped into three main races; Asian (A), Arabo-Bèrbère (B), and Caucasian (C). The Asian volunteers included in this study were from Japan and Singapore. RESULTS: There were statistical differences in the Age, ODI, and BMI of the volunteers from the three different races. Asian volunteers had the lowest age (A: 36.7, B: 45.5, C: 42.0) and BMI (A: 22.1, B: 27.1, C: 27.3). Pelvic morphology including pelvic incidence (A: 51.0, B: 52.0, C: 52.5, p = 0.37), pelvic tilt (A: 11.9, B: 12.3, C: 12.9, p = 0.44), and sacral slope (A: 39.1, B: 39.7, C: 39.6, p = 0.77) were similar amongst the 3 races. Regional spinal alignment was different between the groups. Thoracic Kyphosis (A: 32.9, B: 43.3, C: 40.0, p < 0.0001) and Lumbar lordosis (A: - 54.2, B: - 60.4, C: - 59.6, p < 0.0001) were lower in Asians compared to Caucasian and Arabo-Bèrbère volunteers despite having similar pelvic incidence. CONCLUSION: Volunteers in the Asian group had lower lumbar lordosis and thoracic kyphosis when compared to the Arabo-Bèrbère and Caucasian groups while all groups had similar pelvic morphology. Thoracic Kyphosis had no correlation with Pelvic Incidence, while Lumbar Lordosis correlated well with both Thoracic Kyphosis and Pelvic Incidence. Thoracic kyphosis may be an independent variable in establishing adequate lumbar lordosis and varies based on an individual's race.

Mesenchymal Stromal Cell Exosomes Mediate M2-like Macrophage Polarization through CD73/Ecto-5'-Nucleotidase Activity.

Mesenchymal stem/stromal cell (MSC) exosomes have been shown to alleviate immune dysfunction and inflammation in preclinical animal models. This therapeutic effect is attributed, in part, to their ability to promote the polarization of anti-inflammatory M2-like macrophages. One polarization mechanism has been shown to involve the activation of the MyD88-mediated toll-like receptor (TLR) signaling pathway by the presence of extra domain A-fibronectin (EDA-FN) within the MSC exosomes. Here, we uncovered an additional mechanism where MSC exosomes mediate M2-like macrophage polarization through exosomal CD73 activity. Specifically, we observed that polarization of M2-like macrophages by MSC exosomes was abolished in the presence of inhibitors of CD73 activity, adenosine receptors A2A and A2B, and AKT/ERK phosphorylation. These findings suggest that MSC exosomes promote M2-like macrophage polarization by catalyzing the production of adenosine, which then binds to adenosine receptors A2A and A2B to activate AKT/ERK-dependent signaling pathways. Thus, CD73 represents an additional critical attribute of MSC exosomes in mediating M2-like macrophage polarization. These findings have implications for predicting the immunomodulatory potency of MSC exosome preparations.