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PurposeThere are few epidemiological studies of spinal surgery in Asia and none in Japan. The goal of this study was to review spine surgeries performed in our group between 2004 and 2015 in a cross-sectional study, with a focus on the effects of the superaging society on the characteristics and trends of spinal surgeries.MethodsA retrospective review was performed for all 45,831 spinal surgeries conducted between 2004 and 2015 and recorded in our prospective multicenter database.ResultsDuring the study period, there was a significant increase in annual spine surgeries (p < 0.05). The proportion of elderly patients (aged ≥ 70) also increased, and the mean age at the time of surgery significantly increased from 54.6 years in 2004 to 63.7 years in 2015 (p < 0.05). Regarding the etiology, there were significant increases in degenerative disease (p < 0.01) and osteoporotic vertebral fracture, and a significant decrease in rheumatic spondylosis from 2004 to 2015 (p < 0.01). Instrumentation surgery increased over time, with the performance of MIS, BKP and LLIF as new procedures in recent years (p < 0.01). The mean reoperation rate was 2.0% and this rate did not change significantly over time, although the rate of reoperation due to surgical site infection significantly increased from 0.9 to 1.5% (p < 0.05).ConclusionsOur data showed marked increases in the number of spine surgeries, the age of patients, and the number of surgeries for degenerative diseases. This large-scale study provides indicators for planning the future development of spine surgery and for treatment of spinal diseases in daily practice.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Meningiomas are benign tumors that are treated surgically. Local recurrence is likely if the dura is preserved, and en bloc tumor and dura resection (Simpson grade I) is recommended. In some cases the dura is cauterized and preserved after tumor resection (Simpson grade II). The purpose of this study was performed to analyze clinical features and prognostic factors associated with spinal meningioma, and to identify the most effective surgical treatment. The subjects were 116 patients (22 males, 94 females) with spinal meningioma who underwent surgery at seven NSG centers between 1998 and 2018. Clinical data were collected from the NSG database. Pre- and postoperative neurological status was defined using the modified McCormick scale. The patients had a mean age of 61.2 ± 14.8 years (range 19–91 years) and mean symptom duration of 11.3 ± 14.7 months (range 1–93 months). Complete resection was achieved in 108 cases (94%), including 29 Simpson grade I and 79 Simpson grade II resections. The mean follow-up period was 84.8 ± 52.7 months. At the last follow-up, neurological function had improved in 73 patients (63%), was stable in 34 (29%), and had worsened in 9 (8%). Eight patients had recurrence, and recurrence rates did not differ significantly between Simpson grades I and II in initial surgery. Kaplan–Meier analysis of recurrence-free survival showed that Simpson grade III or IV, male, and dural tail sign were significant factors associated with recurrence (P < 0.05). In conclusion, Simpson I resection is anatomically favorable for spinal meningiomas. Younger male patients with a dural tail and a high-grade tumor require close follow-up. The tumor location and feasibility of surgery can affect the surgical morbidity in Simpson I or II resection. All patients should be carefully monitored for long-term outcomes, and we recommend lifelong surveillance after surgery.

Background Low back pain is often caused by lumbar disc herniation (LDH). Treatment of LDH is possible using chemonucleolysis of the nucleus pulposus with condoliase injection. However, onset of the therapeutic effect varies among patients, with improvement from an early stage to 3 months post-injection. This study was performed to identify the characteristics of early responders to condoliase therapy. Methods A retrospective cohort study was performed in 371 consecutive patients (259 males, 112 females; age, 49.9 ± 18.7 years; follow-up period, 13.1 ± 7.4 months) treated with condoliase injection for LDH between August 2018 and January 2024. Chemonucleolysis was performed with 1 mL of condoliase (1.25 U/mL) injected into the intervertebral nucleus pulposus. Clinical assessments were made before injection and 1 day, and 1, 4 and 12 weeks post-injection. Pain was measured on a visual analogue scale. Herniation parameters were evaluated on axial MRI. The herniated disc volume was measured on plain lumbar radiography. Demographic and clinical data were taken from medical charts. Multivariate logistic regression analysis was used to identify factors with independent relationships with treatment efficacy. Results Improvement of leg pain from baseline by ≥ 50% occurred in 21% of cases within one day after condoliase treatment. Patients with this improvement at 1 week post-injection were defined as early responders (n = 142, 38.3%). In multivariate analysis, age < 40 years ( p  = 0.022, odds ratio (OR): 1.71, 95% confidence interval (CI): 1.12–4.35), Pfirrmann Grade II or III at baseline ( p  = 0.032, OR: 1.86, 95% CI: 1.17–5.41), and a high intensity MRI signal in the herniation ( p  = 0.041, OR: 1.87, 95% CI: 1.06–5.27) were significantly associated with early improvement. No patients had anaphylactic shock or neurologic sequelae. Conclusions This study confirms the safety and efficacy of chemonucleolysis with condoliase for treating patients with painful LDH. Age, high-intensity MRI signals, and baseline Pfirrmann grade were significant factors associated with early improvement.

PurposeTo identify age-related changes and the relationship between upper and lower cervical sagittal alignment and the range of motion (ROM). MethodsA total of 600 asymptomatic volunteers were enrolled. There were 50 males and 50 females in each decade of life between the third and the eighth. The O–C2 angle and the C2–7 angle were measured using the neutral radiographs of the cervical spine. ROM was assessed by measuring the difference in alignment in the neutral, flexion, and extension positions.ResultsThe mean O–C2 angle in the neutral position was 14.0° lordotic. The mean ROM of the O–C2 angle was 23.1°. The mean C2–7 angle in the neutral position was 14.3° lordotic. The mean ROM of the C2–7 angle was 56.0°. The O–C2 angle was 16.1° in the third decade and gradually decreased to 11.4° in the eighth decade. There were no significant age-related changes in the ROM of the O–C2 angle. The C2–7 angle was 7.2° in the third decade and gradually increased to 20.8° in the eighth decade, and the ROM gradually decreased with increasing age. Significant negative correlation was observed between O–C2 angle and C2–7 angle.ConclusionThe O–C2 angle gradually decreased and the C2–7 angle increased with age. The ROM of the O–C2 angle did not change, but the ROM of the C2–7 angle decreased with age. The upper and lower cervical spine showed different age-related changes.

The phase angle, which is measured via bioelectrical impedance analysis (BIA), is a clinically important bioimpedance parameter used for nutritional assessment and evaluating the risk of various diseases, such as locomotive syndrome (LS). It remains unclear if the phase angle is associated with frailty (fragile state of physical and mental health). We therefore examined this association in a large prospective sample. Of 1081 individuals receiving health checkups, 550 (male; 235, female; 365) were enrolled in this study. We applied the Japanese version of the Cardiovascular Health Study criteria to evaluate frailty and administered the 25-Item Geriatric Locomotive Function Scale to diagnose LS. The phase angle was measured via BIA. Multiple logistic regression analysis was used to evaluate the relationship between the phase angle and frailty. For all participants and for each sex, the phase angle was significantly lower among individuals with frailty. After controlling for age, sex, and body mass index, we found that a low phase angle was a significant risk factor of frailty. As a result of multiple regression analysis including other confounding factors, among male participants, a low phase angle was significantly related with both frailty (P = 0.015) and LS (P < 0.001), whereas among female participants, the low phase angle had a stronger association with frailty (P = 0.001) than with LS (P = 0.52). Our findings suggest that a low angle is a risk factor of frailty. Furthermore, among female participants, frailty has a stronger relation with the phase angle than does LS. Therefore, the phase angle may be considered a useful indicator of frailty that does not require lengthy or costly assessment.

Glioma initiating cells (GICs) are thought to contribute to therapeutic resistance and tumor recurrence in glioblastoma, a lethal primary brain tumor in adults. Although the stem-like properties of GICs, such as self-renewal and tumorigenicity, are epigenetically regulated, the role of a major chromatin remodeling complex in human, the SWI/SNF complex, remains unknown in these cells. We here demonstrate that the SWI/SNF core complex, that is associated with a unique corepressor complex through the d4-family proteins, DPF1 or DPF3a, plays essential roles in stemness maintenance in GICs. The serum-induced differentiation of GICs downregulated the endogenous expression of DPF1 and DPF3a , and the shRNA-mediated knockdown of each gene reduced both sphere-forming ability and tumor-forming activity in a mouse xenograft model. Rescue experiments revealed that DPF1 has dominant effects over DPF3a. Notably, whereas we have previously reported that d4-family members can function as adaptor proteins between the SWI/SNF complex and NF-κB dimers, this does not significantly contribute to maintaining the stemness properties of GICs. Instead, these proteins were found to link a corepressor complex containing the nuclear receptor, TLX, and LSD1/RCOR2 with the SWI/SNF core complex. Collectively, our results indicate that DPF1 and DPF3a are potential therapeutic targets for glioblastoma.

Spinal fusion and bone defect after injuries, removal of bone tumors, and infections need to be repaired by implantation. In an aging society, recovery from these procedures is often difficult. In this study, we found that injection of SPG-178 leads to expression of several bone marker genes and mineralization in vitro, and revealed a significantly higher degree of newly formed bone matrix with use of SPG-178 in vivo. MC3T3-E1 cells were used to evaluate osteoblast differentiation promoted by SPG-178. To analyze gene expression, total RNA was isolated from MC3T3-E1 cells cultured for 7 and 14 days with control medium or SPG-178 medium. Among the several bone marker genes examined, SPG-178 significantly increased the mRNA levels for ALP, BMP-2 and Osteocalcin, OPN, BSP and for the Osterix. Ten-week-old female Wistar rats were used for all transplantation procedures. A PEEK cage was implanted into a bony defect (5 mm) within the left femoral mid-shaft, and stability was maintained by an external fixator. The PEEK cages were filled with either a SPG-178 hydrogel plus allogeneic bone chips (n = 4) or only allogeneic bone chips (n = 4). The rats were then kept for 56 days. Newly formed bone matrix was revealed inside the PEEK cage and there was an increased bone volume per total volume with the cage filled with SPG-178, compared to the control group. SPG-178 has potential in clinical applications because it has several benefits. These include its favorable bone conduction properties its ability to act as a support for various different cells and growth factors, its lack of infection risk compared with materials of animal origin such as ECM, and the ease with which it can be used to fill defects with complex shapes and combined with a wide range of other materials.

Study Design: Retrospective analysis of a prospectively database. Objectives: To identify factors associated with prolonged length of stay (LOS) in posterior /transforaminal lumbar interbody fusion (PLIF/TLIF). Methods: The subjects were patients who underwent PLIF/TLIF at 10 facilities from 2012 to 2014. A total of 1168 such patients with a mean age of 65.9 ± 12.5 years (range 18-87 years) were identified in the database. Operations were PLIF (n = 675), TLIF (n = 443), minimally invasive surgery (MIS)-PLIF (n = 22), and MIS-TLIF (n = 32). Age, gender, body mass index, ambulatory status, comorbidities, perioperative American Society of Anesthesiologists (ASA) grade, operative factors, and complications were examined. LOS was defined as the number of calendar days from the operation to hospital discharge. LOS was categorized as normal (<75th percentile) or prolonged (≥75th percentile). Results: The average LOS was 20.8 ± 9.8 days (range 7-77 days). There was a significant correlation between LOS and age (P < .05). Reoperation during hospitalization was performed in 20 cases for surgical site infection (n = 12), epidural hematoma (n = 5), and screw misplacement (n = 3). In multivariate analysis, prolonged LOS was associated with preoperative variables of age ≥70 years (odds ratio [OR] 1.87, 95% CI 1.38-2.54), and ASA class ≥III (OR 1.52, 95% CI 1.04-2.25); surgical variables of open procedures (OR 5.84, 95% CI 1.74-19.63), fused levels ≥3 (OR 5.17, 95% CI 3.17-8.43), operative time ≥300 minutes (OR 1.88, 95% CI 1.15-3.07), and estimated blood loss ≥500 mL (OR 1.71, 95% 1.07-2.75). Conclusions: The factors identified in this study should help with obtaining informed consent, surgical planning and complication prevention to reduce health care costs associated with prolonged LOS.

PurposePelvic incidence (PI) is unique to each individual and does not change throughout life. High PI is related to lumbar spondylolisthesis, but associations of PI with lumbar osteophyte formation and disc degeneration are unclear. The objective was to evaluate relationships of PI with lumbar osteophyte formation and disc degeneration, as well as spinal sagittal alignment and geriatric diseases, in middle-aged and elderly people.MethodsA total of 1002 volunteers (male: 434, female: 568, average age: 63.5) were prospectively examined for lumbar osteophyte formation (Nathan class ≥ 2) and disc degeneration (disc score ≥ 3). High (PI > 51, n = 501) and low (PI ≤ 51, n = 501) PI groups were defined. Clinical factors, frailty, sarcopenia, and physical quality of life (QOL) were compared between these groups, and risk factors for lumbar osteophyte formation and disc degeneration were identified in multivariate logistic regression analysis.ResultsPhysical QOL was poorer in people with lumbar osteophyte formation (54.8%) and disc degeneration (33.6%). Age, male gender, spinal parameters including PI, bone mineral density, back muscle strength, and gait ability differed significantly between the groups, whereas frailty and sarcopenia were not significantly different. Low PI, low lumbar lordosis, elder age, male gender, high BMI, and weak back muscle strength were significant risk factors for lumbar osteophyte formation and disc degeneration.ConclusionsLow PI was identified as a risk factor for lumbar osteophyte formation and disc degeneration, both of which reduce physical QOL in middle-aged and elderly people.Graphic abstractThese slides can be retrieved under Electronic Supplementary Material.

PurposeTandem spinal stenosis (TSS) refers to coexisting lumbar and cervical canal stenosis. Evidence regarding whether cervical decompression improves lumbar symptoms in TSS is insufficient. Therefore, we determined the effectiveness of cervical decompression surgery for patients with lumbar spinal stenosis (LSS) and cervical spinal stenosis. MethodsThe records of 64 patients with TSS experiencing lumbar symptoms who underwent cervical decompression surgery between April 2013 and July 2017 at a single institution were retrospectively reviewed. We categorized patients into the Non-improved (n = 20), Relapsed (n = 30), and Maintained-improvement (n = 14) groups according to the presence or absence of improvement and relapse in lower limb symptoms in TSS following cervical decompression surgeries.ResultsOf 64 patients, 44 (69%) showed improved lower limb or low back symptoms, with 14 (22%) patients maintaining improvement. The preoperative cervical myelopathy-Japanese Orthopedic Association score and the preoperative number of steps determined using the 10-s step test were significantly lower in the Non-improved group than in the Maintained-improvement group. Receiver operating characteristic curve of preoperative 10-s step test results revealed 12 steps as a predictor for maintained improvement.ConclusionThe improvement of LSS symptoms following cervical decompression surgeries may be associated with the severity of cervical myelopathy as determined in clinical findings rather than in imaging findings. Patients with TSS having a 10-s step test result of < 12 steps were more likely to experience a relapse of lower limb symptoms following cervical decompression surgeries.