Unveiling the natural history of paralysis in metastatic cervical spinal tumor: An experimental study.

Introduction: Despite the relatively low prevalence of metastatic cervical spinal tumor, these entities give rise to more profound complications than thoracic and lumbar spinal tumor. However, it is regrettable that experimental investigation has thus far shown a dearth of attention to metastatic cervical spinal tumor. Research question: What is the conceptualization and realization of quadriparesis resulting from metastatic cervical spinal tumor? Material and methods: Using Fischer 344 rats as the experimental cohort, this study orchestrated the engraftment of tumor cells procured from the 13762 MAT B III cell line (RRID: CVCL_3475), which represents mammary adenocarcinoma. These cells were engrafted into the vertebrae of the cervical spine. A comprehensive inquiry encompassing behavioral assessments, histological evaluations, and microangiographic analyses conducted after the aforementioned cellular transplantation was subsequently pursued. Results: The incidence of cervical paralysis was 61.1%. Notably, the evolution of paralysis was unfurled by two distinctive temporal phases within its natural history. A meticulous histological examination facilitated delineation of the tumor's posterior expansion within the spinal canal. Simultaneously, the tumor exhibited anterior and lateral encroachment on the spinal cord, inducing compression from all sides. Augmented by microangiographic investigations, conspicuous attenuation of stained blood vessels within the affected anterior horn and funiculus of the spinal cord was observed. Discussion and conclusion: The pathological advancement of paralysis stemming from metastatic cervical spinal tumor is now apprehended to unfurl through a biphasic phase. The initial phase is characterized by gradual unfurling spanning several days, juxtaposed against the second phase marked by swift and accelerated progression.

The Validation of the Japanese Version of the Scoliosis Research Society-30 Questionnaire for Adolescent Idiopathic Scoliosis Patients.

Introduction: The Scoliosis Research Society-30 (SRS-30) is a questionnaire originally developed from the SRS-22r questionnaire and is used to evaluate adolescent idiopathic scoliosis (AIS). It comprised questions on five domains: function, pain, self-image, mental health, and satisfaction, with seven additional questions related to postoperative aspects. In addition to the original English version, translations in multiple languages have been effectively applied. Herein, we evaluated the internal consistency and external validity of the Japanese version of the SRS-30 for AIS patients. Methods: Among the 30 questions in SRS-30, the eight additional questions from SRS-22r were translated and back-translated to create a Japanese version of the SRS-30. This translated questionnaire was then used to survey patients with AIS who underwent corrective fusion surgery one year postoperatively. The internal consistency of the responses was evaluated using the Cronbach α coefficient. Additionally, the Spearman correlation analyses were conducted to assess the correlation between the scores obtained from the SRS-30 Japanese version and SRS-22r and the Oswestry Disability Index (ODI) for the overall scale and the five domains. Results: A total of 81 cases (eight males and 73 females; mean age at surgery 14.4 years) were enrolled. The mean preoperative Cobb angle was 51.0°. The Cronbach α coefficient for the overall SRS-30 was 0.861, indicating high internal consistency, while the coefficients for each domain were as follows: function/activity, 0.697; pain, 0.405; self-image/appearance, 0.776; mental health, 0.845; and satisfaction, 0.559. The SRS-30 total score significantly correlated with the SRS-22r total (r=0.945, P<0.001) and the ODI (r=-0.511, P<0.001). The SRS-30 domains highly correlated with the corresponding SRS-22r domains, with correlations ranging from r=0.826 to 0.901 (all P<0.001). Conclusions: The Japanese version of the SRS-30 demonstrated good internal and external validity. The SRS-30 can be used as an assessment tool for health-related quality of life in AIS patients.

Factors Associated with the Maintenance of Cost-Effectiveness at 5 Years in Adult Spinal Deformity Corrective Surgery.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate factors associated with the long-term durability of cost-effectiveness (CE) in ASD patients. BACKGROUND: A substantial increase in costs associated with the surgical treatment for adult spinal deformity (ASD) has given precedence to scrutinize the value and utility it provides. METHODS: We included 327 operative ASD patients with 5-year (5 Y) follow-up. Published methods were used to determine costs based on CMS.gov definitions and were based on the average DRG reimbursement rates. Utility was calculated using quality-adjusted life-years (QALY) utilizing the Oswestry Disability Index (ODI) converted to Short-Form Six-Dimension (SF-6D), with a 3% discount applied for its decline with life expectancy. The CE threshold of $150,000 was used for primary analysis. RESULTS: Major and minor complication rates were 11% and 47% respectively, with 26% undergoing reoperation by 5 Y. The mean cost associated with surgery was $91,095±$47,003, with a utility gain of 0.091±0.086 at 1Y, QALY gained at 2 Y of 0.171±0.183, and at 5 Y of 0.42±0.43. The cost per QALY at 2 Y was $414,885, which decreased to $142,058 at 5 Y.With the threshold of $150,000 for CE, 19% met CE at 2 Y and 56% at 5 Y. In those in which revision was avoided, 87% met cumulative CE till life expectancy. Controlling analysis depicted higher baseline CCI and pelvic tilt (PT) to be the strongest predictors for not maintaining durable CE to 5 Y (CCI OR: 1.821 [1.159-2.862], P=0.009) (PT OR: 1.079 [1.007-1.155], P=0.030). CONCLUSIONS: Most patients achieved cost-effectiveness after four years postoperatively, with 56% meeting at five years postoperatively. When revision was avoided, 87% of patients met cumulative cost-effectiveness till life expectancy. Mechanical complications were predictive of failure to achieve cost-effectiveness at 2 Y, while comorbidity burden and medical complications were at 5 Y.

Comparison of the Fixation Strengths of Screws between the Traditional Trajectory and the Single and Double Endplate Penetrating Screw Trajectories Using Osteoporotic Vertebral Body Models Based on the Finite Element Method.

STUDY DESIGN: This is a finite element (FE) study. PURPOSE: To compare the fixation strength of traditional trajectory (TT) and single and double endplate penetrating screw trajectories (SEPST/DEPST) to the osteoporotic vertebral body model based on the FE method. OVERVIEW OF LITERATURE: SEPST/DEPST have been developed to enhance the fixation strength in patients with diffuse idiopathic hyperostosis (DISH). This technique was also applied to patients with osteoporosis. However, determining the superiority of SEPST/ DEPST is difficult because of the heterogeneous patient backgrounds. METHODS: Twenty vertebrae (T12 and L1) from 10 patients with osteoporosis (two males and eight females; mean age, 74.7 years) were obtained to create the 10 FE models. First, a single screw was placed with TT and SEPST/DEPST, and the fixation strength was compared by axial pullout strength (POS) and multidirectional loading tests. Second, two screws were placed on the bilateral pedicles with TT and SEPST/DEPST, and the fixation force of the vertebrae in the constructs in flexion, extension, lateral flexion, and axial rotation was examined. RESULTS: SEPST and DEPST had 140% and 171% higher POS values than TT, respectively, and the DEPST result was statistically significant (p =0.007). The multidirectional fixation strength was significantly higher in DEPST and SEPST than in TT in the cranial, caudal, and medial directions (p <0.05) but not in the lateral direction (p =0.05). The vertebral fracture strength at the lower instrumented vertebra of the DEPST tended to be higher than that of TT. The vertebral motion angles in SEPST and DEPST were significantly smaller in lateral bending (p =0.02) and tended to be smaller in flexion and extension than in TT (p =0.13). CONCLUSIONS: This study may provide useful information for spine surgeons in deciding whether to choose the SEPS or DEPS technique for augmenting fixation in osteoporotic vertebral fracture surgery.

Predictors of pelvic tilt normalization: a multicenter study on the impact of regional and lower-extremity compensation on pelvic alignment after complex adult spinal deformity surgery.

OBJECTIVE: The objective was to determine the degree of regional decompensation to pelvic tilt (PT) normalization after complex adult spinal deformity (ASD) surgery. METHODS: Operative ASD patients with 1 year of PT measurements were included. Patients with normalized PT at baseline were excluded. Predicted PT was compared to actual PT, tested for change from baseline, and then compared against age-adjusted, Scoliosis Research Society-Schwab, and global alignment and proportion (GAP) scores. Lower-extremity (LE) parameters included the cranial-hip-sacrum angle, cranial-knee-sacrum angle, and cranial-ankle-sacrum angle. LE compensation was set as the 1-year upper tertile compared with intraoperative baseline. Univariate analyses were used to compare normalized and nonnormalized data against alignment outcomes. Multivariable logistic regression analyses were used to develop a model consisting of significant predictors for normalization related to regional compensation. RESULTS: In total, 156 patients met the inclusion criteria (mean ± SD age 64.6 ± 9.1 years, BMI 27.9 ± 5.6 kg/m2, Charlson Comorbidity Index 1.9 ± 1.6). Patients with normalized PT were more likely to have overcorrected pelvic incidence minus lumbar lordosis and sagittal vertical axis at 6 weeks (p < 0.05). GAP score at 6 weeks was greater for patients with nonnormalized PT (0.6 vs 1.3, p = 0.08). At baseline, 58.5% of patients had compensation in the thoracic and cervical regions. Postoperatively, compensation was maintained by 42% with no change after matching in age-adjusted or GAP score. The patients with nonnormalized PT had increased rates of thoracic and cervical compensation (p < 0.05). Compensation in thoracic kyphosis differed between patients with normalized PT at 6 weeks and those with normalized PT at 1 year (69% vs 35%, p < 0.05). Those who compensated had increased rates of implant complications by 1 year (OR [95% CI] 2.08 [1.32-6.56], p < 0.05). Cervical compensation was maintained at 6 weeks and 1 year (56% vs 43%, p = 0.12), with no difference in implant complications (OR 1.31 [95% CI -2.34 to 1.03], p = 0.09). For the lower extremities at baseline, 61% were compensating. Matching age-adjusted alignment did not eliminate compensation at any joint (all p > 0.05). Patients with nonnormalized PT had higher rates of LE compensation across joints (all p < 0.01). Overall, patients with normalized PT at 1 year had the greatest odds of resolving LE compensation (OR 9.6, p < 0.001). Patients with normalized PT at 1 year had lower rates of implant failure (8.9% vs 19.5%, p < 0.05), rod breakage (1.3% vs 13.8%, p < 0.05), and pseudarthrosis (0% vs 4.6%, p < 0.05) compared with patients with nonnormalized PT. The complication rate was significantly lower for patients with normalized PT at 1 year (56.7% vs 66.1%, p = 0.02), despite comparable health-related quality of life scores. CONCLUSIONS: Patients with PT normalization had greater rates of resolution in thoracic and LE compensation, leading to lower rates of complications by 1 year. Thus, consideration of both the lower extremities and thoracic regions in surgical planning is vital to preventing adverse outcomes and maintaining pelvic alignment.

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Nationwide Survey of the Surgical Complications Associated with Lateral Lumbar Interbody Fusion in 2015-2020.

Introduction: Lateral lumbar interbody fusion (LLIF) has been introduced in Japan in 2013. Despite the effectiveness of this procedure, several considerable complications have been reported. This study reported the results of a nationwide survey performed by the Japanese Society for Spine Surgery and Related Research (JSSR) on the complications associated with LLIF performed in Japan. Methods: JSSR members conducted a web-based survey following LLIF between 2015 and 2020. Any complications meeting the following criteria were included: (1) major vessel, (2) urinary tract, (3) renal, (4) visceral organ, (5) lung, (6) vertebral, (7) nerve, and (8) anterior longitudinal ligament injury; (9) weakness of psoas; (10) motor and (11) sensory deficit; (12) surgical site infection; and (13) other complications. The complications were analyzed in all LLIF patients, and the differences in incidence and type of complications between the transpsoas (TP) and prepsoas (PP) approaches were compared. Results: Among the 13,245 LLIF patients (TP 6,198 patients [47%] and PP 7,047 patients [53%]), 389 complications occurred in 366 (2.76%) patients. The most common complication was sensory deficit (0.5%), followed by motor deficit (0.43%) and weakness of psoas muscle (0.22%). Among the patient cohort, 100 patients (0.74%) required revision surgery during the survey period. Almost half of the complications developed in patients with spinal deformity (183 patients [47.0%]). Four patients (0.03%) died from complications. Statistically more frequent complications occurred in the TP approach than in the PP approach (TP vs. PP, 220 patients [3.55%] vs. 169 patients [2.40%]; p<0.001). Conclusions: The overall complication rate was 2.76%, and 0.74% of the patients required revision surgery because of complications. Four patients died from complications. LLIF may be beneficial for degenerative lumbar conditions with acceptable complications; however, the indication for spinal deformity should be carefully determined by the experience of the surgeon and the extent of the deformity.

Evaluation of intraoperative coronal alignment using a computer-assisted rod bending system (CARBS) without intraoperative radiation exposure in adult spinal deformity surgery: a technical note and preliminary results.

PURPOSE: Intraoperative radiographs and fluoroscopy are used in adult spinal deformity (ASD) surgery to prevent postoperative coronal malalignment but with limited accuracy. Therefore, we applied a computer-assisted rod bending system (CARBS: Bendini®) for an intraoperative coronal alignment evaluation. The purpose of this study is to introduce this novel technique and validate its accuracy. METHODS: Fifteen ASD patients were included in the study. The heads of the bilateral S1 pedicle screws (S1), the S1 spinous process, and the bilateral greater trochanter (GT) and the C7 spinous process were recorded with CARBS for an intraoperative coronal alignment evaluation. The lines which connect the bilateral S1 and GT were used as references. The C7-center sacral vertical line (C7-CSVL) on the CARBS monitor was checked, and the C7-CSVL from the intraoperative CARBS recording and postoperative standing whole spine radiograph were compared. RESULTS: Intraoperative C7-CSVL with CARBS was 35.1 ± 31.6 mm when the S1 pedicle screws were used as the reference line and was 16.6 ± 17.8 mm when the GTs were used. Postoperative C7-CSVL by radiograph was 15.1 ± 16.5 mm. In addition, the intraoperative C7-CSVL with CARBS and the postoperative C7-CSVL showed a strong positive correlation in both GT (R = 0.86, p < 0.01) and in S1(R = 0.79, p < 0.01), with a better correlation found in GT than in S1. CONCLUSION: Intraoperative C7-CSVL with CARBS was found to be highly accurate in ASD surgery. Our results suggest that this novel technique can be useful as an alternative to intraoperative radiography and fluoroscopy and may reduce radiation exposure.

Relationship between the 25-question Geriatric Locomotive Function Scale and physical function in the elderly people.

INTRODUCTION: Locomotive syndrome (LS) is a condition of reduced mobility. The LS stage can be determined by the stand-up test, two-step test, and 25-question geriatric locomotive function scale (GLFS-25). This study aimed to establish whether the LS stage can be reliably determined using the GLFS-25, and to clarify the correlation between the GLFS-25's six subcategories and physical functions. MATERIALS AND METHODS: We administered the GLFS-25 and evaluated physical functions using the stand-up test, the two-step test, handgrip strength, the five-times sit-to-stand test, the 4 m walking test, and the duration of single leg standing. We assessed 103 participants over 65 years of age. We analyzed the correlation between LS stage and GLFS-25 score, as well as the correlations between physical functions and the GLFS-25's six subcategories. RESULTS: There was a discrepancy between the LS stage determined using the GLFS-25 alone and the LS stage determined using all three tools. ROC analysis revealed a cut-off value of 6 for the discrimination of LS stages 0/1 and 14 for stages 1/2. The analysis revealed an AUC of 0.78 and 0.81, respectively. Among the six subcategories of the GLFS-25, movement-related difficulty, usual care, ADL, and social activities were correlated with mobility functions. In contrast, body pain and cognitive showed no correlation. CONCLUSION: The GLFS-25 is useful for screening those with severe LS stages; however, evaluation of actual physical function is recommended for precise staging of LS in those with low GFLS-25 scores. Among the six subcategories of the GLFS-25, body pain and cognitive were independent of the other four subcategories.

Comparable satisfaction and clinical outcomes after surgery for adolescent idiopathic scoliosis in the adult (AISA) between the US and Japan.

BACKGROUND: The impact of ethnicity on the surgery outcomes of adolescent idiopathic scoliosis in the adult (AISA) is poorly understood. This study aimed to compare the surgery outcomes for AISA between the United States (US) and Japan (JP). METHODS: 171 surgically treated AISA (20-40y) were consecutively collected from 2 separate multicenter databases. Patients were propensity-score matched for age, gender, curve type, levels fused, and 2y postop spinal alignment. Demographic and radiographic parameters were compared between the US and JP at baseline and 2y post-op. RESULTS: A total of 108 patients were matched by propensity score (age; US vs. JP: 29 ± 6 vs. 29 ± 7y, females: 76 vs. 76%, curve type [Schwab-SRS TypeT; TypeD; TypeL; TypeN]: 35; 35; 30; 0 vs. 37; 33; 30; 0%)] levels fused: 10 ± 4 vs. 10 ± 4, 2y thoracic curve:17 ± 13 vs. 17 ± 12°, 2y CSVL: 10 ± 8 vs. 11 ± 9 mm). Similar clinical improvement was achieved between US and JP (function; 4.2 ± 0.9 vs 4.3 ± 0.6, p = 0.60, pain; 3.8 ± 0.9 vs 4.1 ± 0.8, p = 0.13, satisfaction; 4.3 ± 0.9 vs 4.2 ± 0.7, p = 0.61, total; 4.0 ± 0.8 vs 4.1 ± 0.5, p = 0.60). The correlation analyzes indicated that postoperative SRS-22 subdomains correlated differently with satisfaction (all subdomains moderately correlated with satisfaction in the US while only pain and mental health correlated moderately with satisfaction in JP ([function: r = 0.61 vs 0.29, pain: r = . 72 vs 0.54, self-image: r = 0.72 vs 0.37, mental health: r = 0.64 vs 0.55]). CONCLUSIONS: Surgery for AISA was similarly effective in the US and JP. Satisfaction for spinal surgery among patients in different countries may not be different unless the procedure limits an individual's unique lifestyle that the patient expected to resume.

Abrogation of LBX1 in skeletal muscle results in hypoplastic limbs and progressive kyphosis in mice.

LBX1 is a gene located near a single-nucleotide polymorphism, rs11190870, which is highly associated with susceptibility to adolescent idiopathic scoliosis. However, the potential involvement of LBX1 in the etiology of this spinal deformity has not been elucidated. In this study, we aimed to determine whether the lack of LBX1 in skeletal muscle results in spinal deformities in mice. We generated mutant mice in which the Lbx1 allele was conditionally excised under the control of a human muscle actin promoter. Mice lacking LBX1 from the skeletal muscle were fertile and available. The mutant mice had hypoplastic forelimbs and weighed less than control animals, but otherwise, there were no overt anomalies. The mice did not exhibit a scoliosis-like spinal deformity; however, they developed moderate kyphosis as they grew old. These observations indicated that LBX1 is involved in limb development and potentially in the maintenance of spinal curvature/alignment in mice.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Risk factors for early reoperation in patients after posterior lumbar interbody fusion surgery. A propensity-matched cohort analysis.

BACKGROUND: Reoperation is usually associated with poor results and increased morbidity and hospital costs. However, the rates, causes, and risk factors for reoperation in patients undergoing lumbar spinal fusion surgery remain controversial. This study aimed to identify the risk factors for early reoperation after posterior lumbar interbody fusion surgery and to compare the clinical outcomes between patients who underwent reoperation and those who did not. METHODS: We investigated a multicenter medical record database of 1263 patients who underwent posterior lumbar interbody fusion surgery between 2012 and 2015. A total of 72 (5.7%) reoperations within two years after surgery were identified and were propensity-matched for age, sex, number of fusion segments, and surgeon's experience. RESULTS: We analyzed a total of 114 patients (57 who underwent reoperation (R group) and 57 who did not (C group)). The mean age was 62.6 ± 13.4 years, with 78 men and 36 women. The mean number of fused segments was 1.2 ± 0.5. Surgical site infection was the most common cause of reoperation. There were significant differences in the incidence of diabetes mellitus (p = 0.024), preoperative ambulation status (p = 0.046), and ASA grade (p < 0.001) between the C and R groups. The recovery rate of the Japanese Orthopaedic Association score was significantly lower in the R group compared to the C group (R: 50.5 ± 28.8%, C: 63.9 ± 33.7%, p = 0.024). There were significant differences in the bone fusion rate (R: 63.2%, C: 96.5%, p < 0.001) and incidence of screw loosening (R: 31.6%; C: 10.5%; p = 0.006). CONCLUSION: Diabetes mellitus, preoperative ambulation status, and ASA grade were significant risk factors for early reoperation following posterior lumbar interbody fusion surgery. The patients who underwent early reoperation had worse clinical outcomes than those who did not.

Optimal timing for intermittent administration of parathyroid hormone (1-34) for distraction osteogenesis in rabbits.

BACKGROUND: To date, the usefulness of parathyroid hormone [PTH (1-34)] in distraction osteogenesis has been reported in several studies. We aimed to determine the optimal timing of PTH (1-34) administration in a rabbit distraction osteogenesis model. METHODS: The lower hind leg of a Japanese white rabbit was externally fixed, and tibial osteotomy was performed. One week after the osteotomy, bone lengthening was carried out at 0.375 mm/12 h for 2 weeks. After 5 weeks, the lower leg bone was collected. Bone mineral density (BMD), peripheral quantitative computed tomography (pQCT), micro-computed tomography (micro-CT), and mechanical tests were performed on the distracted callus. The rabbits were divided into three groups according to the timing of PTH (1-34) administration: 4 weeks during the distraction and consolidation phases (group D + C), 2 weeks of the distraction phase (group D), and the first 2 weeks of the consolidation phase (group C). A control group (group N) was administered saline for 4 weeks during the distraction and consolidation phases. Furthermore, to obtain histological findings, lower leg bones were collected from each rabbit at 2, 3, and 4 weeks after osteotomy, and tissue sections of the distracted callus were examined histologically. RESULTS: The BMD was highest in group C and was significantly higher than group D. In pQCT, the total cross-sectional area was significantly higher in groups D + C, D, and C than group N, and the cortical bone area was highest in group C and was significantly higher than group D. In micro-CT, group C had the highest bone mass and number of trabeculae. Regarding the mechanical test, group C had the highest callus failure strength, and this value was significantly higher compared to group N. There was no significant difference between groups D and N. The histological findings revealed that the distracted callus mainly consisted of endochondral ossification in the distraction phase. In the consolidation phase, the chondrocytes were almost absent, and intramembranous ossification was the main type of ossification. CONCLUSION: We found that the optimal timing of PTH (1-34) administration is during the consolidation phase, which is mainly characterized by intramembranous ossification.

Radiological Evaluation of Combined Anteroposterior Fusion with Vertebral Body Replacement Using a Minimally Invasive Lateral Approach for Osteoporotic Vertebral Fractures: Verification of Optimal Surgical Procedure.

The combined anteroposterior fusion with vertebral body replacement (VBR) using a wide footplate expandable cage with a minimally invasive lateral approach has been widely used for pseudoarthrosis after osteoporotic vertebral fractures. The purpose of this study is to evaluate the radiological results of combined anteroposterior surgery using VBR and to recommend the optimal procedure. Thirty-eight elderly patients were included in this study. The mean preoperative local kyphosis angle was 29.3°, and the mean correction loss angle was 6.3°. Cage subsidence was observed in ten patients (26.3%), and UIV or LIV fracture in twelve patients (31.6%). Patients with cage subsidence were compared to those without cage subsidence to determine the causal factors. The mean number of fixed vertebrae was 5.4 vertebrae with cage subsidence and 7.4 vertebrae without cage subsidence. In addition, to precisely clarify the optimal number of fixed vertebrae, those patients with two above-two below fixation were compared to those with less than two above-two below fixation, which revealed that the correction loss angle was significantly less in two above-two below fixation (p = 0.016). Based on these results, we recommend at least two above-two below fixation with VBR to minimize the correction loss angle and prevent cage subsidence.

Improvement and International Validation of the Predictive Probability of the Patient Demographics, Radiographic Index, and Surgical Invasiveness for Mechanical Failure (PRISM) Model for Preventive Procedures in Adult Spinal Deformity Surgery.

STUDY DESIGN: This is an international multicenter retrospective review of 219 surgically treated consecutive adult spinal deformity (ASD) patients who had a minimum of five fused segments, completed a 2-year follow-up. OBJECTIVE: The purpose of this study was to add the indices of preventive procedures to improve and to validate the predictive probability of the PRISM (patient demographics, radiographic index, and surgical invasiveness for mechanical failure) for mechanical failure (MF) following ASD surgery. SUMMARY OF BACKGROUND DATA: The PRISM was developed from the data of 321 ASD patients, which stratified the risk of MF from six types of risk. METHODS: Data from 136 Japanese ASD patients (age 49 ±â€Š21 yr, 88% female) were used to develop PRISM2, and data from 83 US ASD patients (age 58 ±â€Š12 yr, 86% female) were used for the external validation. We analyzed the associations between three preventive procedures (UIV+1 tethering [TH], teriparatide [TP], and multirod [MR]) and MF by multivariate logistic regression analysis (MRA). The values for the nearest integer of the ß of the procedures were added to the six indices of the original PRISM to establish the PRISM2. The discriminative ability of the PRISM/ PRISM2 for MF was evaluated using the area under the receiver operating characteristic curve (AUC) and the precision-recall (PR) curve. The Cochran-Armitage test was used to analyze the trend between PRISM/PRISM2 scores and MF. RESULTS: MF developed in 25% (34 cases). The ß values for the preventive procedures calculated by MRA were TH: -2.5, TP: -3.0, and MR: -2.1. The Cochran-Armitage test showed an excellent trend between MF and PRISM/2. The diagnostic ability was superior for the PRISM2 compared with the PRISM (PRISM2; AUC = 0.94 [0.90-0.98], PRISM; AUC = 0.87 [0.81-0.93], difference = -0.07 [-0.11 to -0.03], P  < 0.01). The AUC of the PRISM2 was 0.70 [0.59-0.81, P < 0.01] in the US patient cohort. CONCLUSION: We refined the PRISM by adding preventive procedures to the risk indices. Further validation and adjustment in a large different patient cohorts may improve the predictive probability of PRISM2.Level of Evidence: 3.

Effect of low body mass index on clinical recovery after fusion surgery for osteoporotic vertebral fracture: A retrospective, multicenter study of 237 cases.

A retrospective multicenter study. Body mass index (BMI) is recognized as an important determinant of osteoporosis and spinal postoperative outcomes; however, the specific impact of BMI on surgery for osteoporotic vertebral fractures (OVFs) remains inconclusive. This retrospective multicenter study investigated the impact of BMI on clinical outcomes following fusion surgery for OVFs. 237 OVF patients (mean age, 74.3 years; 48 men and 189 women) with neurological symptoms who underwent spinal fusion were included in this study. Patients were grouped by World Health Organization BMI categories: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2), and high BMI (≥25 kg/m2). Patients' backgrounds, surgical method, radiological findings, pain measurements, activities of daily living (ADL), and postoperative complications were compared after a mean follow-up period of 4 years. As results, the proportion of patients able to walk independently was significantly smaller in the low BMI group (75.0%) compared with the normal BMI group (89.9%; P = .01) and the high BMI group (94.3%; P = .04). Improvement in the visual analogue scale for leg pain was significantly less in the low BMI group than the high BMI group (26.7 vs 42.8 mm; P = .046). Radiological evaluation, the Frankel classification, and postoperative complications were not significantly different among all 3 groups. Improvement of pain intensity and ADL in the high BMI group was equivalent or non-significantly better for some outcome measures compared with the normal BMI group. Leg pain and independent walking ability after fusion surgery for patients with OVFs improved less in the low versus the high BMI group. Surgeons may want to carefully evaluate at risk low BMI patients before fusion surgery for OVF because poor clinical results may occur.

Risk predictors of perioperative complications for the palliative surgical treatment of spinal metastasis.

BACKGROUND: The complication rate for palliative surgery in spinal metastasis is relatively high, and major complications can impair the patient's activities of daily living. However, surgical indications are determined based primarily on the prognosis of the cancer, with the risk of complications not truly considered. We aimed to identify the risk predictors for perioperative complications in palliative surgery for spinal metastasis. METHODS: A multicentered, retrospective review of 195 consecutive patients with spinal metastasis who underwent palliative surgeries with posterior procedures from 2001 to 2016 was performed. We evaluated the type and incidence of perioperative complications within 14 days after surgery. Patients were categorized into either the complication group (C) or no-complication group (NC). Univariate and multivariate analyses were used to identify potential predictors for perioperative complications. RESULTS: Thirty patients (15%) experienced one or more complications within 14 days of surgery. The most frequent complications were surgical site infection (4%) and motor weakness (3%). A history of diabetes mellitus (C; 37%, NC; 9%: p < 0.01) and surgical time over 300 min (C; 27%, NC; 12%: p < 0.05) were significantly associated with complications according to univariate analysis. Increased blood loss and non-ambulatory status were determined to be potential risk factors. Of these factors, multivariate logistic regression revealed that a history of diabetes mellitus (OR: 6.6, p < 0.001) and blood loss over 1 L (OR: 2.7, p < 0.05) were the independent risk factors for perioperative complications. There was no difference in glycated hemoglobin A1c between the diabetes patients with and without perioperative complications. CONCLUSIONS: Diabetes mellitus should be used for the risk stratification of surgical candidates regardless of the treatment status, and strict prevention of bleeding is needed in palliative surgeries with posterior procedures to mitigate the risk of perioperative complications.

Polygenic Risk Score of Adolescent Idiopathic Scoliosis for Potential Clinical Use.

Adolescent idiopathic scoliosis (AIS) is a common disease causing three-dimensional spinal deformity in as many as 3% of adolescents. Development of a method that can accurately predict the onset and progression of AIS is an immediate need for clinical practice. Because the heritability of AIS is estimated as high as 87.5% in twin studies, prediction of its onset and progression based on genetic data is a promising option. We show the usefulness of polygenic risk score (PRS) for the prediction of onset and progression of AIS. We used AIS genomewide association study (GWAS) data comprising 79,211 subjects in three cohorts and constructed a PRS based on association statistics in a discovery set including 31,999 female subjects. After calibration using a validation data set, we applied the PRS to a test data set. By integrating functional annotations showing heritability enrichment in the selection of variants, the PRS demonstrated an association with AIS susceptibility (p = 3.5 × 10-40 with area under the receiver-operating characteristic [AUROC] = 0.674, sensitivity = 0.644, and specificity = 0.622). The decile with the highest PRS showed an odds ratio of as high as 3.36 (p = 1.4 × 10-10 ) to develop AIS compared with the fifth in decile. The addition of a predictive model with only a single clinical parameter (body mass index) improved predictive ability for development of AIS (AUROC = 0.722, net reclassification improvement [NRI] 0.505 ± 0.054, p = 1.6 × 10-8 ), potentiating clinical use of the prediction model. Furthermore, we found the Cobb angle (CA), the severity measurement of AIS, to be a polygenic trait that showed a significant genetic correlation with AIS susceptibility (rg = 0.6, p = 3.0 × 10-4 ). The AIS PRS demonstrated a significant association with CA. These results indicate a shared polygenic architecture between onset and progression of AIS and the potential usefulness of PRS in clinical settings as a predictor to promote early intervention of AIS and avoid invasive surgery. © 2021 American Society for Bone and Mineral Research (ASBMR).

Characterization of Patients with Poor Risk for Clinical Outcomes in Adult Symptomatic Lumbar Deformity Surgery.

STUDY DESIGN: Retrospective review of 159 surgically treated consecutive adult symptomatic lumbar deformity (ASLD) (65 ±â€Š9 years, female: 94%) from a multicenter database. OBJECTIVE: The aim of this study was to provide a comprehensive analysis of the risk of a poor clinical outcome in ASLD surgery. SUMMARY OF BACKGROUND DATA: Poor-risk patients with ASLD remain poorly characterized. METHODS: ASLD was defined as age >40 years with a lumbar curve ≥30° or C7SVA ≥5 cm and Scoliosis Research Society 22 (SRS22) pain or function <4. Poor outcome was defined as 2y SRS22 total <4 or pain, function or satisfaction ≤3. The outcomes of interest included age, sex, body mass index, bone mineral density, Schwab-SRS type, frailty, history of arthroplasty, upper-instrumented vertebral, lower-instrumented vertebral, levels involved, pedicle subtraction osteotomy, lumbar interbody fusion, sagittal alignment, global alignment and proportion (GAP) score, baseline SRS22r score, estimated blood loss, time of surgery, and severe adverse event (SAE). Poisson regression analyses were performed to identify the independent risks for poor clinical outcome. A patient was considered at poor risk if the number of risks was >4. RESULTS: All SRS22 domains were significantly improved after surgery. In total, 21% (n = 34) reported satisfaction ≤3 and 29% (n = 46) reported pain or function ≤3. Poisson regression analysis revealed that frailty (odds ratio [OR]: 0.2 [0.1-0.8], P = .03), baseline mental-health (OR: 0.6 [0.4-0.9], P = .01) and function (OR: 1.9 [1.0-3.6], P < .01), GAP score (OR: 4.6 [1.1-18.7], P = .03), and SAE (OR: 3.0 [1.7-5.2], P < .01) were identified as independent risk for poor clinical outcome. Only 17% (n = 6) of the poor-risk patients reached SRS22 total score >4.0 at 2 years. CONCLUSION: The overall clinical outcome was favorable for ASLD surgery. Poor-risk patients continue to have inferior outcomes, and alternative treatment strategies are needed to help improve outcomes in this patient population. Recognition and optimization of modifiable risk factors, such as physical function and mental health, and reduced SAEs may improve overall clinical outcomes of ASLD surgery.Level of Evidence: 3.