Pelvic thickness, sex, ethnicity, and age affect pelvic incidence in healthy volunteers of Multi-Ethnic Alignment Normative Study (MEANS) database.

BACKGROUND: The purpose of this study was to investigate the affecting factors on pelvic incidence (PI) and to test the hypothesis that PI changes even after skeletal maturity probably due to hypermobility of the sacroiliac joint using a large international multi-center database. METHODS: A prospective and cross-sectional healthy adult volunteers, ages 18-80 years, across 5 countries were used. Radiographic measurements included standard whole body alignment parameters. Bivariate regression analyses between PI versus demographics and spino-pelvic anatomical parameters were performed. An effect of sex on pelvic anatomical parameters was also investigated. Multivariate logistic regression with a forward stepwise procedure was performed to identify the contributing factors to PI, and an appropriate model was obtained. RESULTS: PI showed a significant positive correlation with age in pooled data. Divided by sex, however, there was no correlation in men, but women showed a significant higher correlation coefficient. Pelvic thickness (PTh) had a significant negative correlation with age in pooled data. Divided by sex, no correlation was found in men, but there was a significant correlation in women with higher correlation coefficient. The stepwise multivariate analysis for the factors on PI identified four significant factors: age, sex, ethnicity, and PTh. CONCLUSIONS: PTh, sex, ethnicity, and age affected PI. There was a positive correlation between PI and age. The tendency was more significant in woman than in man. The results support the hypothesis that PI increases with aging, but the change seems to be small and needs to be verified in a longitudinal evaluation.

Correlation analysis of the PI-LL mismatch according to the pelvic incidence from a database of 468 asymptomatic volunteers.

PURPOSE: Previous studies on adults with degenerative scoliosis (ADS) have been fixed the threshold of PI-LL mismatch less than 10° for achieving good clinical outcomes. Recent studies discussed that PI-LL mismatch should consider individual pelvic incidence (PI) and should be set first in a normal population. The purpose of this study is to assess the variability of PI-LL mismatch according to PI in an asymptomatic population. METHODS: Full-body low dose stereoradiographic evaluation was done in a multi-ethnic cohort of 468 asymptomatic adult volunteers. Patients were clustered in three groups depending on individual PI values: PI < 45°, 45° < PI < 60° and PI > 60°. 3D measurements were performed using a commercially available 2D/3D modeling software to establish a correlation of PI with other spinopelvic parameters. ANOVA and Tukey's HSD for post-hoc analysis were used to determine the differences between the three groups. RESULTS: In our asymptomatic population, the mean value of PI-LL mismatch is - 5.4° ± 10.7°. Clusterization of the population reveals significant differences in the distribution of L1S1 lordosis, pelvic tilt and PI-LL with positive linear correlation according to PI values. As an interestingly result, PI-LL mismatch is equal to 0° when PI is around 64°. CONCLUSIONS: The present study demonstrated that PI-LL mismatch is negative in an asymptomatic population (- 5.4° ± 10.7°) and the value should be customized to each patient to be able to restore the appropriate lordosis in ADS. The PI-LL mismatch is given by the formula PI-LL = - 28.5 + 0.44 × PI.

ProDisc-C versus anterior cervical discectomy and fusion for the surgical treatment of symptomatic cervical disc disease: two-year outcomes of Asian prospective randomized controlled multicentre study.

PURPOSE: Our study aimed to evaluate non-inferiority of ProDisc-C to anterior cervical discectomy and fusion (ACDF) in terms of clinical outcomes and incidence of adjacent segment disease (ASD) at 24-months post-surgery in Asian patients with symptomatic cervical disc disease (SCDD). METHODS: This multicentre, prospective, randomized controlled trial was initiated after ethics committee approval at nine centres (China/Hong Kong/Korea/Singapore/Taiwan). Patients with single-level SCDD involving C3-C7-vertebral segments were randomized (2:1) into: group-A treated with ProDisc-C and group-B with ACDF. Assessments were conducted at baseline, 6-weeks, 3/6/12/18/24-months post-surgery and annually thereafter till 84-months. Primary endpoint was overall success at 24-months, defined as composite of: (1) ≥ 20% improvement in neck disability index (NDI); (2) maintained/improved neurologic parameters; (3) no implant removal/revision/re-operation at index level; and (4) no adverse/severe/life-threatening events. RESULTS: Of 120 patients (80ProDisc-C,40ACDF), 76 and 37 were treated as per protocol (PP). Overall success (PP) was 76.5% in group-A and 81.8% in group-B at 24-months (p = 0.12), indicating no clear non-inferiority of ProDisc-C to ACDF. Secondary outcomes improved for both groups with no significant inter-group differences. Occurrence of ASD was higher in group-B with no significant between-group differences. Range of motion (ROM) was sustained with ProDisc-C but lost with ACDF at 24-months. CONCLUSION: Cervical TDR with ProDisc-C is feasible, safe, and effective for treatment of SCDD in Asians. No clear non-inferiority was demonstrated between ProDisc-C and ACDF. However, patients treated with ProDisc-C demonstrated significant improvement in NDI, neurologic success, pain scores, and 36-item-short-form survey, along with ROM preservation at 24-months. Enrolment difficulties resulted in inability to achieve pre-planned sample size to prove non-inferiority. Future Asian-focused, large-scale studies are needed to establish unbiased efficacy of ProDisc-C to ACDF.

Analysis of unplanned hospital readmissions up to 2-years after metastatic spine tumour surgery.

PURPOSE: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education. METHODS: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis. RESULTS: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis. CONCLUSION: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.

A novel hospital capacity versus clinical justification triage score (CCTS) for prioritization of spinal surgeries in the "new normal state" of the COVID-19 pandemic.

INTRODUCTION: During the Coronavirus disease 2019 outbreak, while healthcare systems and hospitals are diverting their resources to combat the pandemic, patients who require spinal surgeries continue to accumulate. The aim of this study is to describe a novel hospital capacity versus clinical justification triage score (CCTS) to prioritize patients who require surgery during the "new normal state" of the COVID-19 pandemic. METHODOLOGY: A consensus study using the Delphi technique was carried out among clinicians from the Orthopaedic Surgery, Neurosurgery, and Anaesthesia departments. Three rounds of consensus were carried out via survey and Webinar discussions. RESULTS: A 50-points score system consisting of 4 domains with 4 subdomains was formed. The CCTS were categorized into the hospital capacity, patient factors, disease severity, and surgery complexity domains. A score between 30 and 50 points indicated that the proposed operation should proceed without delay. A score of less than 20 indicates that the proposed operation should be postponed. A score between 20 and 29 indicates that the surgery falls within a grey area where further discussion should be undertaken to make a joint justification for approval of surgery. CONCLUSION: This study is a proof of concept for the novel CCTS scoring system to prioritize surgeries to meet the rapidly changing demands of the COVID-19 pandemic. It offers a simple and objective method to stratify patients who require surgery and allows these complex and difficult decisions to be unbiased and made transparently among surgeons and hospital administrators.

The odontoid-CSVL distance in a global population of asymptomatic volunteers: normative values and implications for spinal coronal alignment.

PURPOSE: In a population of asymptomatic volunteers across 5 countries, we sought to: (a) establish normative values of the Odontoid-Central Sacral Vertical Line (OD-CSVL) across patient factors, and (b) assess correlations of OD-CSVL with other radiographic parameters. METHODS: A prospective, cross-sectional study of asymptomatic adult volunteers, ages 18-80 years, were enrolled across 5 countries (France, Japan, Singapore, Tunisia, United States) forming the Multi-Ethnic Alignment Normative Study (MEANS) cohort. Included volunteers had no known spinal disorder(s), no significant neck/back pain (VAS ≤ 2; ODI ≤ 20), and no significant scoliosis (Cobb ≤ 20°). Radiographic measurements included commonly used coronal alignment parameters (mm) and angles (°). OD-CSVL was defined as the difference between the odontoid plumb line (line from the tip of the odontoid vertically down) and the CSVL (vertical line from the center of the sacrum). Chi-square, student's t tests, Kruskal-Wallis, Wilcoxon rank-sum, linear regression, and Pearson's correlation were used with significance at p < 0.05. RESULTS: 467 volunteers were included with normative OD-CSVL values by age decade, gender, BMI, and country. Mean ± SD OD-CSVL was 8.3 mm ± 6.5 mm and 31 (6.6%) volunteers were almost perfectly aligned (OD-CSVL < 1 mm). A linear relationship was seen between OD-CSVL with both age (p < 0.001) and BMI (p = 0.015). Significant variation was seen between OD-CSVL and 5 different ethnicities (p = 0.004). OD-CSVL correlated best with other coronal radiographic parameters, C7-CSVL (r = 0.743, p < 0.001), OD-knee (r = 0.230, p < 0.001), CAM-knee (r = 0.612, p < 0.001), and regional TL cobb angle (r = 0.4214, p = 0.005). CONCLUSION: Among asymptomatic volunteers, increased OD-CSVL was significantly associated with increased age, increased BMI, and ethnicity, but not gender. OD-CSVL correlated strongest with C7-CSVL, TL cobb angle, OD-knee, and CAM-knee. OD-CSVL. These results support further study of OD-CSVL in symptomatic adult spine deformity patients.

Is MIS-TLIF superior to open TLIF in obese patients?: A systematic review and meta-analysis.

PURPOSE: Obesity is a global health problem. It increases the risk of surgical complications and re-operations. While both MIS-TLIF and O-TLIF are reported to have comparably good long-term outcomes for non-obese patients, no consensus has been reached for obese patients. METHODS: A comprehensive search of the published literature was performed: PubMed, Scopus, Web of Science and Cochrane Central Register of Controlled Trials database in accordance to the PRISMA 2009 checklist. Data were collected with attention to baseline demographics, intra-operative blood loss, duration of surgery, surgical complications, hospitalization stay, VAS and Oswestry disability index (ODI) pre- and postoperatively. RESULTS: A total of 863 abstracts were identified from the databases, of which 4 articles were included in the meta-analysis. A total of 430 patients were identified, of which 217(50.5%) underwent the O-TLIF, while 213(49.5%) underwent MIS-TLIF. One hundred and ninety-four (45.1%) patients were males, while 236(54.9%) were females. The average age was 54.8 ± 12.0 years. The pooled BMI was 33.4 ± 4.7 for the open-TLIF group, and 32.7 ± 3.9 for MIS-TLIF group (p = 0.22). When comparing O-TLIF to MIS-TLIF: Patients who underwent O-TLIF had 383 mls more blood loss (95% CI: 329.5-437.4, p < 0.00001), 1.2-day longer hospitalization stay (95% CI: 0.80-1.62, p < 0.00001) and 3.8 times higher risk of dural tear (95% CI: 1.61-9.87, p = 0.003) when compared to MIS-TLIF patients. A trend toward higher postoperative wound infection rates (O-TLIF: 4.5%, MIS-TLIF: 2.4%) and an inferior improvement in ODI score (O-TLIF: 39.3, MIS-TLIF: 44.1) was found in O-TLIF patients when compared to MIS-TLIF patients. However, these were not statistically significant. CONCLUSION: MIS-TLIF is safe and may be a better option for lumbar fusion in obese patients. These slides can be retrieved under Electronic Supplementary Material.

Normal variation in sagittal spinal alignment parameters in adult patients: an EOS study using serial imaging.

PURPOSE: To describe normal variations in sagittal spinal radiographic parameters over an interval period and establish physiological norms and guidelines for which these images should be interpreted. METHODS: Data were prospectively collected from a continuous series of adult patients with first-episode mild low back pain presenting to a single institution. The sagittal parameters of two serial radiographic images taken 6-months apart were obtained with the EOS® slot scanner. Measured parameters include CL, TK, TL, LL, PI, PT, SS, and end and apical vertebrae. Chi-squared test and Wilcoxon Signed Rank test were used to compare categorical and continuous variables, respectively. RESULTS: Sixty patients with a total of 120 whole-body sagittal X-rays were analysed. Mean age was 52.1 years (SD 21.2). Mean interval between the first and second X-rays was 126.2 days (SD 47.2). Small variations (< 1°) occur for all except PT (1.2°), CL (1.2°), and SVA (2.9 cm). Pelvic tilt showed significant difference between two images (p = 0.035). Subgroup analysis based on the time interval between X-rays, and between the first and second X-rays, did not show significant differences. Consistent findings were found for end and apical vertebrae of the thoracic and lumbar spine between the first and second X-rays for sagittal curve shapes. CONCLUSIONS: Radiographic sagittal parameters vary between serial images and reflect dynamism in spinal balancing. SVA and PT are predisposed to the widest variation. SVA has the largest variation between individuals of low pelvic tilt. Therefore, interpretation of these parameters should be patient specific and relies on trends rather than a one-time assessment.

Delayed lymphocele formation following lateral lumbar interbody fusion of the spine.

PURPOSE: This paper aims to describe the rare post-operative complication of a lymphocele formation after lateral lumbar interbody fusion. METHODS: The patient in this case was a 76-year-old lady with a 10 year history of low back pain and neurogenic claudication. She had previously underwent multiple spine surgeries for her condition. She presented to our institution for a recurrence of her low back pain and right anterior thigh pain. She then underwent surgery in two stages; first, a mini-open lateral interbody fusion at L3/4 and L4/5; second, posterior instrumentation of T3 to S1 with sagittal spinal deformity correction. RESULTS: The patient recovered uneventfully in the initial post op period and was discharged within 8 days. However, she developed abdominal distension and discomfort 6 months after surgery. MRI and CT scan of her abdomen showed a retroperitoneal fluid collection compressing her left ureter, resulting in hydroureter and hydronephrosis. She was managed with a CT-guided drainage of the fluid collection. Fluid analysis was consistent with a lymphocele. Since the procedure, the patient has been asymptomatic for 2 years. CONCLUSIONS: Delayed lymphocele formation is a potential complication of lateral lumbar interbody fusion. When present, it can be managed conservatively with good results. This case suggests that surgeons should have a low threshold to investigate for a lymphocele development post-anterior or lateral lumbar spine surgery. The authors recommend the placement of a post surgical retroperitoneal drain, as it might assist in the early detection of a lymphocele formation.

Three-dimensional development of tensile pre-strained annulus fibrosus cells for tissue regeneration: an in-vitro study.

Prior research has investigated the immediate response after application of tensile strain on annulus fibrosus (AF) cells for the past decade. Although mechanical strain can produce either catabolic or anabolic consequences to the cell monolayer, little is known on how to translate these findings into further tissue engineering applications. Till to date, the application and effect of tensile pre-strained cells to construct a three-dimensional (3D) AF tissue remains unknown. This study aims to investigate the effect of tensile pre-strained exposure of 1 to 24h on the development of AF pellet culture for 3 weeks. Equibiaxial cyclic tensile strain was applied on AF monolayer cells over a period of 24h, which was subsequently developed into a cell pellet. Investigation on cellular proliferation, phenotypic gene expression, and histological changes revealed that tensile pre-strain for 24h had significant and lasting effect on the AF tissue development, with enhanced cell proliferation, and up-regulation of collagen type I, II, and aggrecan expression. Our results demonstrated the regenerative ability of AF cell pellets subjected to 24h tensile pre-straining. Knowledge on the effects of tensile pre-strain exposure is necessary to optimize AF development for tissue reconstruction. Moreover, the tensile pre-strained cells may further be utilized in either cell therapy to treat mild disc degeneration disease, or the development of a disc construct for total disc replacement.

Minimally invasive iliac screw fixation in treating painful metastatic lumbosacral deformity: a technique description and clinical results.

INTRODUCTION: Pelvic fixation via iliac screws is a crucial technique in stabilizing metastatic lumbosacral deformity. MIS iliac screw fixation avoids complications of an open approach and is a viable palliative option in treating patients with painful instability and advanced disease, unsuited for major reconstruction. In this paper we describe the use of MIS iliac screw fixation in treatment of painful metastatic LSJ deformity, highlighting our treatment rationale, selection criteria, technical experience and outcomes. METHODS: Five patients with lumbosacral metastatic deformity who underwent MIS lumbopelvic stabilization using iliac screws were prospectively studied. Patients had severe axial back pain in erect posture with significant resolution when supine. All patients had advanced disease with unfavorable tumor scores for major spinal reconstruction. RESULTS: Mean cohort age was 62 years. Median pre-op SIN and Tokuhashi scores were 13 and 9, respectively. All patients were instrumented successfully without conversion to open technique. Mean preoperative and postoperative Cobb angle was 11° and 5.4°, respectively. There were no neurological deficits or wound complications postop. Postoperative CT scans showed no iliac screw and sacroiliac joint bony violation. Mean time for commencement of adjuvant therapy was 2.8 weeks. Average follow-up was 13.2 months. No screw breakage, wound complication, symptomatic implant prominence and SI joint pain were noted at last follow-up. CONCLUSION: MIS iliac screw fixation is feasible, reproducible and can be employed without complications in metastatic spine. This opens a new avenue of surgical management for metastatic lumbosacral disease patients, who otherwise may be inoperable and provide better soft tissue control and earlier postoperative adjuvant treatment opportunity.

Are we ready for the use of intraoperative salvaged blood in metastatic spine tumour surgery?

PURPOSE: To evaluate the feasibility of using intraoperative cell salvage (IOCS) in combination with leucocyte depletion filter (LDF) in eliminating tumour cells from blood salvaged during metastatic spine tumour surgery (MSTS). This is with the view to pave the path for use of IOCS-LDF in MSTS and musculoskeletal oncological surgery. METHODS: Sixty consecutive patients with known primary epithelial tumour, who were offered surgery for metastatic spine disease at our university hospital, were recruited. Blood samples were collected at three different stages during surgery: from operative field prior to IOCS processing, after IOCS processing and after IOCS-LDF processing. Three separate samples (5 ml each) were taken at each stage. Samples were examined by cell block technique using immunohistochemical monoclonal antibodies to identify tumour cells of epithelial origin in the samples. RESULTS: Of 60 patients, ten were excluded for not fulfilling the inclusion criteria leaving 50 patients. Malignant tumour cells were detected in the samples from operative field prior to IOCS processing in 24 patients and in the samples from the transfusion bag post-IOCS processing in 4 patients. No viable malignant cells were detectable in any of the blood samples after passage through both IOCS and LDF. CONCLUSIONS: The findings support the notion that IOCS-LDF combination works effectively in eliminating tumour cells from salvaged blood so this technique can possibly be applied in MSTS and even musculoskeletal oncological surgery. This concept can then be extended to other oncological surgeries in general with further appropriate clinical studies.

Long-term Follow-up of Pulmonary Function and Scoliosis in Patients With Duchenne's Muscular Dystrophy and Spinal Muscular Atrophy.

BACKGROUND: Spine surgery for neuromuscular scoliosis in patients with Duchenne's Muscular Dystrophy (DMD) and Spinal Muscular Atrophy (SMA) remained controversial. This study aimed to review the long-term results of spine surgery and its effect on pulmonary function in these patients. METHODS: A retrospective review was conducted for the above patients who had undergone surgery from 1990 to 2006 in a tertiary hospital. Their yearly lung function tests, clinical records, and x-ray films before and after surgery were reviewed. All patients had at least 2 lung function tests performed before surgery and at least 3 lung function tests performed after surgery. Records of perioperative pulmonary infections that resulted in hospital admissions were also retrieved from the hospital computer system. RESULTS: Forty patients were reviewed: 29 with DMD, 11 with SMA. The mean follow-up period was 11.6 years. For patients with DMD, the mean correction of Cobb's angle from surgery was 34.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 7.80% per year, and was reduced to 4.26% per year postoperatively (P<0.001). For patients with SMA, the mean correction of Cobb's angle from surgery was 44.1 degrees. The rate of decline of the predicted forced vital capacity preoperatively was 5.31% per year, and was reduced to 1.77% per year postoperatively (P<0.001). For both DMD and SMA patients, the difference between the rate of preoperative and postoperative pulmonary infections that resulted in hospital admission were, however, not significant (P=0.433 and 0.452, respectively). CONCLUSIONS: Scoliosis surgery in patients with DMD and SMA results in a long-term decreased rate of decline in pulmonary function over a follow-up period of more than 10 years. The level of the apical vertebrae of the scoliosis did not demonstrate a significant trend on the pulmonary function. The frequency of chest infections did not improve by scoliosis surgery. LEVEL OF SIGNIFICANCE: Level III­Retrospective study.

Versatility of percutaneous pedicular screw fixation in metastatic spine tumor surgery: a prospective analysis.

BACKGROUND: Posterior percutaneous spinal fixation (PPSF) has evolved to address the problems associated with metastatic spinal disease (MSD). This study was designed to evaluate the feasibility and spectrum of application of PPSF in the management of MSD, highlighting its clinical advantages. METHODS: Twenty-seven consecutive patients with MSD treated with PPSF in our institution from January 2011 to June 2014 were studied. After a multidisciplinary assessment, all patients were considered for surgical intervention due to clinical presentation of either neural deficit, skeletal instability, or both. Some of these patients belonged to the poor prognostic category based on survival prognostic scoring systems. The patients were categorized into seven groups depending on the modality of PPSF used. Demographic data, operative details, and clinical outcomes were investigated for each category and compared pre- and postoperatively. RESULTS: The median age was 60 years (range 49-78 years). Generally, all patients either maintained or improved their neurological status and achieved pain alleviation. Ambulatory status and Eastern Cooperative Oncology Group (ECOG) scores were improved using any modality of PPSF. The pure-stabilization group had the lowest amount of mean blood loss, shortest operative time, and intensive care unit (ICU) and hospital stays, while the long-construct group was observed to have the greatest amount of blood loss, and longest operative time and ICU stay. CONCLUSIONS: For patients with MSD, even with predicted poor prognosis on survival prognostic scoring systems, it is possible to improve functional outcomes and quality of life with PPSF, keeping surgical morbidity to a minimum. PPSF allows patients with pure spinal instability to be addressed successfully with least morbidity.

Can there be a place for intraoperative salvaged blood in spine tumor surgery?

BACKGROUND: Intraoperative cell salvage (IOCS) has been used in musculoskeletal surgery extensively. However, it has never found its place in musculoskeletal oncologic surgery. We have conducted the first-ever study to evaluate the feasibility of IOCS in combination with a leucocyte-depletion filter (LDF) in metastatic spine tumor surgery. This was to pave the path for use of IOCS-LDF in musculoskeletal oncologic surgery. METHODS: Patients with a known primary epithelial tumor, who were offered surgery for metastatic spinal disease, were recruited. Blood samples were collected at three different stages during the surgery: from the operative field before IOCS processing, after IOCS processing, and after IOCS-LDF processing. Three separate samples (5 mL each) were taken at each stage. Samples were examined using immunohistochemical monoclonal antibodies to identify tumor cells of epithelial origin. RESULTS: Of 30 patients in the study, 6 were excluded for not fulfilling the inclusion criteria, leaving 24 patients. Malignant tumor cells were detected in the samples from the operative field before IOCS processing in eight patients and in the samples from the transfusion bag after IOCS processing in three patients. No viable malignant cell was detectable in any of the blood samples after passage through both IOCS and LDF. CONCLUSIONS: The findings support the notion that the IOCS-LDF combination works effectively in eliminating tumor cells from salvaged blood, so this technique can be applied successfully in spine tumor surgery. This concept can then further be extended to whole musculoskeletal tumor surgery and other oncologic surgeries with further appropriate clinical studies.

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.

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.

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.

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.

Silk fibroin-based complex particles with bioactive encrustation for bone morphogenetic protein 2 delivery.

Application of bone morphogenetic protein 2 (BMP-2) currently faces its challenges, and its efficacy of delivery has to be improved. The proper dosage of the powerful bioactive molecule is still under discussion and needs to be investigated further. In this work, pure silk fibroin particles and particles with calcium carbonate encrustation (complex particles) are designed, developed, and functionalized by BMP-2. These are used to deliver the bioactive molecule to mesenchymal stem cells (MSCs) to induce osteogenic differentiation. Results are compared with those of control groups of BMP-2 carriers under the same condition. Silk fibroin-based particles with size and component variations are prepared by self-assembly, desolvation, and soft template formation to improve BMP-2 loading efficiency. Results show that the particles significantly enhance osteogenic differentiation of MSCs, which is evident in the high ALP enzyme activity as well as the increased level of expression of osteogenic genes. Specifically, the combination of calcium compound and BMP-2 in the silk fibroin-calcium carbonate complex particles synergistically enhances osteogenesis. Release tests and mathematical modeling are applied to describe BMP-2 dissolution profiles, and the release mechanism is based on diffusion and polymer chain relaxation. In summary, the particles show high efficacies of BMP-2 delivery, and introduction of the complex particle can progressively enhance osteogenesis.