Impact of pathogenic FBN1 variant types on the development of severe scoliosis in patients with Marfan syndrome.

BACKGROUND: Among the several musculoskeletal manifestations in patients with Marfan syndrome, spinal deformity causes pain and respiratory impairment and is a great hindrance to patients' daily activities. The present study elucidates the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. METHODS: We retrospectively evaluated 278 patients with pathogenic or likely pathogenic FBN1 variants. The patients were divided into those with (n=57) or without (n=221) severe scoliosis. Severe scoliosis was defined as (1) patients undergoing surgery before 50 years of age or (2) patients with a Cobb angle exceeding 50° before 50 years of age. The variants were classified as protein-truncating variants (PTVs), which included variants creating premature termination codons and inframe exon-skipping, or non-PTVs, based on their location and predicted amino acid alterations, and the effect of the FBN1 genotype on the development of severe scoliosis was examined. The impact of location of FBN1 variants on the development of severe scoliosis was also investigated. RESULTS: Univariate and multivariate analyses revealed that female sex, PTVs of FBN1 and variants in the neonatal region (exons 25-33) were all independent significant predictive factors for the development of severe scoliosis. Furthermore, these factors were identified as predictors of progression of existing scoliosis into severe state. CONCLUSIONS: We elucidated the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. Patients harbouring pathogenic FBN1 variants with these genetic risk factors should be monitored carefully for scoliosis progression.

Patients with a large ossification of the posterior longitudinal ligament have a higher incidence of arteriosclerosis in the carotid artery.

PURPOSE: This study aimed to investigate the impact of the severity of cervical ossification of the posterior longitudinal ligament (OPLL) on the incidence of arteriosclerosis in the carotid artery. METHODS: Patients with OPLL-induced cervical myelopathy were prospectively enrolled. The study involved analyzing patient characteristics, blood samples, computed tomography scans of the spine, and intima-media thickness (IMT) measurements of the common carotid artery. Patients were divided into two groups based on the size of the cervical OPLL to compare demographic data, comorbidities, and the presence of thickening of the carotid intima-media (max IMT ≥ 1.1 mm). RESULTS: The study included 96 patients (mean age: 63.5 years; mean body mass index: 26.9 kg/m2; 71.8% male; 35.4% with diabetes mellitus). The mean maximum anteroposterior (AP) diameter of the OPLL was 4.9 mm, with a mean occupancy ratio of 43%. The mean maximum IMT was 1.23 mm. Arteriosclerosis of the carotid artery was diagnosed in 62.5% of the patients. On comparing the two groups based on OPLL size, the group with larger OPLL (≥ 5 mm) had a higher BMI and a greater prevalence of carotid intima-media thickening. This significant difference in the prevalence of carotid intima-media thickening persisted even after adjusting for patient backgrounds using propensity score matching. CONCLUSIONS: Patients with a larger cervical OPLL showed a higher frequency of intima-media thickening in the carotid artery.

Reliability and head-loading effects in imaging diagnosis of vertical subluxation in patients with rheumatoid arthritis.

OBJECTIVES: The purpose of this study was to examine the reproducibility of vertical subluxation (VS) parameters using X-ray, computed tomography (CT), and tomosynthesis (TS) while comparing the head-loading effects. METHODS: The VS parameters of 26 patients (retrospective review) were evaluated. Using the intra-class correlation coefficient, we statistically examined the intra-rater and inter-rater reliabilities of the parameters. Head-loaded and -unloaded imagings were compared using a Wilcoxon signed-rank test. RESULTS: The intra-rater reliability of TS and CT showed intra-class correlation coefficients of ≥0.8 (X-ray range: 0.6-0.8), with similar results for the inter-rater reliabilities. Furthermore, in head-loading imaging, the TS had significantly higher VS scores than that of CT (P < .05). CONCLUSIONS: In comparison with the X-ray, TS and CT were more accurate and reproducible. In terms of head loading, the VS values for TS were worse than those for CT, indicating that TS was more effective than CT in diagnosing VS.

Predictors for hemostatic thrombin-gelatin matrix usage in spine surgery: a multicenter observational study.

STUDY DESIGN: A prospective cohort study. OBJECTIVES: Thrombin-gelatin matrix (TGM) is a rapid and potent hemostatic agent, but it has some limitations, including the cost and its preparation time. The purpose of this study was to investigate the current trend in the use of TGM and to identify the predictors for TGM usage in order to ensure its proper use and optimized resource allocation. METHODS: A total of 5520 patients who underwent spine surgery in a multicenter study group within a year were included in the study. The demographic factors and the surgical factors including spinal levels operated, emergency surgery, reoperation, approach, durotomy, instrumented fixation, interbody fusion, osteotomy, and microendoscopy-assistance were investigated. TGM usage and whether it was routine or unplanned use for uncontrolled bleeding were also checked. A multivariate logistic regression analysis was used to identify predictors for unplanned use of TGM. RESULTS: Intraoperative TGM was used in 1934 cases (35.0%), among which 714 were unplanned (12.9%). Predictors of unplanned TGM use were female gender (adjusted odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.02-1.43, p = 0.03), ASA grade ≥ 2 (OR: 1.34, 95% CI: 1.04-1.72, p = 0.02), cervical spine (OR: 1.55, 95% CI: 1.24-1.94, p < 0.001), tumor (OR: 2.02, 95% CI: 1.34-3.03, p < 0.001), posterior approach (OR: 1.66, 95% CI: 1.26-2.18, p < 0.001), durotomy (OR: 1.65, 95% CI: 1.24-2.20, p < 0.001), instrumentation (OR: 1.30, 1.03-1.63, p = 0.02), osteotomy (OR: 5.00, 2.76-9.05, p < 0.001), and microendoscopy (OR: 2.24, 1.84-2.73, p < 0.001). CONCLUSIONS: Many of the predictors for unplanned TGM use have been previously reported as risk factors for intraoperative massive hemorrhaging and blood transfusion. However, other newly revealed factors can be predictors of bleeding that is technically challenging to control. While routine usage of TGM in these cases will require further justification, these novel findings are valuable for implementing preoperative precautions and optimizing resource allocation.

Does surgical site infection affect patient-reported outcomes after spinal surgery? A multicenter cohort study.

BACKGROUND: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes. METHODS: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups. RESULTS: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups. CONCLUSIONS: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections.

Does T1 slope minus cervical lordosis mismatch affect surgical outcomes of cervical laminoplasty in the absence of preoperative severe kyphosis?

BACKGROUND: The impact of the T1 slope minus cervical lordosis (T1S-CL) on surgical outcomes in patients with degenerative cervical myelopathy undergoing laminoplasty (LP) remain uncertain. METHODS: One hundred patients who underwent cervical LP were retrospectively reviewed. Radiographic measurements included C2-C7 lordosis (CL), T1 slope (T1S), and C2-C7 sagittal vertical axis (SVA). Additionally, pain numeric rating scale, neck disability index (NDI), 12-Item Short-Form Health Survey, Euro QOL 5 dimensions (EQ5D), and Japanese Orthopedic Association score were investigated. According to past reports, T1S-CL > 20° was defined as mismatched. Then, based on T1S-CL mismatching, patients were divided into 2 groups. RESULTS: This research understudied 67 males and 33 females with a mean age of 67 y. Preoperatively, only eight patients showed a T1S-CL mismatch. While the C2-7 Cobb angles did not change significantly after surgery, the T1 slope (T1S) angle increased, increasing the T1S-CL as a result. As we compared the clinical outcomes based on the preoperative T1S-CL mismatching, there were no significant differences between the two groups. On the other hand, the number of patients in the mismatched group increased to 21 patients postoperatively. As we compared clinical outcomes based on the postoperative T1S-CL mismatching, the postoperative NDI score and preop/postop EQ5D score were significantly worse in the mismatch group. CONCLUSIONS: Although cervical LP showed inferior outcomes in patients with postoperative T1S-CL mismatch even in the absence of severe preoperative kyphosis (> 10°), preoperative T1S-CL mismatch was not adversely prognostic.

Postoperative outcomes after degenerative lumbar spine surgery in rheumatoid arthritis patients -a propensity score-matched analysis.

BACKGROUND: Although treatment options for rheumatoid arthritis (RA) have evolved significantly since the introduction of biologic agents, degenerative lumbar disease in RA patients remains a major challenge. Well-controlled comparisons between RA patients and their non-RA counterparts have not yet been reported. The objective of the present study was to compare postoperative outcomes of lumbar spine surgery between RA and non-RA patients by a retrospective propensity score-matched analysis. METHODS: Patients who underwent primary posterior spine surgery for degenerative lumbar disease in our prospective multicenter study group between 2017 and 2020 were enrolled. Demographic data including age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, diabetes mellitus, smoking, steroid usage, number of spinal levels involved, and preoperative patient-reported outcome (PRO) scores (numerical rating scale [NRS] for back pain and leg pain, Short Form-12 physical component summary [PCS], EuroQOL 5-dimension [EQ-5D], and Oswestry Disability Index [ODI]) were used to calculate a propensity score for RA diagnosis. One-to-one matching was performed and 1-year postoperative outcomes were compared between groups. RESULTS: Among the 4567 patients included, 90 had RA (2.0%). RA patients in our cohort were more likely to be female, with lower BMI, higher ASA grade and lower current smoking rate than non-RA patients. Preoperative NRS scores for leg pain, PCS, EQ-5D, and ODI were worse in RA patients. Propensity score matching generated 61 pairs of RA and non-RA patients who underwent posterior lumbar surgery. After background adjustment, RA patients reported worse postoperative PCS (28.4 vs. 37.2, p = 0.008) and EQ-5D (0.640 vs. 0.738, p = 0.03), although these differences were not significant between RA and non-RA patients not on steroids. CONCLUSIONS: RA patients showed worse postoperative quality of life outcomes after posterior surgery for degenerative lumbar disease, while steroid-independent RA cases showed equivalent outcomes to non-RA patients.

Surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with Meyerding grade 2 degenerative spondylolisthesis: a multicenter cohort study.

BACKGROUND: Whether lumbar decompression with fusion surgery is effective against Meyerding grade 2 degenerative spondylolisthesis (DS) is unknown. Therefore, the current study aimed to compare the surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with grade 2 DS with central canal stenosis. METHODS: This retrospective cohort study included prospectively registered patients (n = 3863) who underwent surgery for degenerative lumbar spinal canal stenosis at nine high-volume spine centers from April 2017 to July 2019. Patients with grade 2 DS and central canal stenosis were included in the analysis. Patients with radiculopathy, including foraminal stenosis, degenerative scoliosis, and concomitant anterior spinal fusion, and those with a previous history of lumbar surgery were excluded. The participants were divided into the decompression alone group (group D) and decompression with fusion surgery group (group F). Data about patient-reported outcomes, including Numeric Rating Scale (low back pain, leg pain, leg numbness, and foot numbness), Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 2 years postoperatively. RESULTS: In total, 2354 (61%) patients, including 42 (1.8%) with grade 2 DS (n = 18 in group D and n = 24 in group F), completed the 2-year follow-up. Group D had a higher proportion of female patients than group F. However, the two groups did not significantly differ in terms of other baseline demographic characteristics. Group D had a significantly shorter surgical time and lower volume of intraoperative blood loss than group F. Postoperative patient-reported outcomes did not significantly differ between the two groups, although the preoperative degree of low back pain was higher in group F than in group D. The slip degree of group D did not worsen during the follow-up period. CONCLUSION: The surgical outcomes were similar regardless of the addition of fusion surgery among patients with grade 2 DS. Decompression alone was superior to decompression with fusion surgery as it was associated with a lower volume of intraoperative blood loss and shorter surgical time.

Risk factors for worsening sexual function after lumbar spine surgery and characteristics of non-responders to the questionnaire of sex life.

PURPOSE: To precisely assess the Oswestry Disability Questionnaire (ODQ) and its total score (Oswestry Disability Index: ODI) and reveal characteristics of non-responders of the 8th item of ODQ (ODI-8) relating to sexual function. Furthermore, we evaluated risk factors for aggravation of postoperative sexual function. METHODS: We enrolled patients undergoing lumbar spine surgery at eight hospitals between April 2017 and November 2018. Patients' background data and operative factors were collected. We also assessed pain or dysesthesia (lower back, buttock, leg, and plantar area) on a numerical rating scale, EuroQol 5 Dimension, core outcome measures index back, and ODI before and 1 year after surgery. Factor analysis was conducted for the ODQ. Non-responders of the ODI-8 were compared with full-responders using propensity score matching. Risk factors for worsening ODI-8 were evaluated by multivariate logistic regression analysis. RESULTS: Of the 2,610 patients enrolled, 601 (23.0%) answered all but the ODI-8 item; these patients were likely to show better preoperative clinical symptoms than full-responders, even after adjusting for age and gender using propensity scores. Age, spinal deformity, and the American Society of Anesthesiologists physical status (ASA-PS) 3/4 were significant risk factors for postoperative aggravation of the ODI-8. Factor analysis revealed that the ODQ was composed of dynamic and static activities; the ODI-8 was considered a dynamic activity. CONCLUSION: Almost a fourth of the patients skipped the ODI-8. Age, the presence of spinal deformity, and worse ASA-PS were found to be risk factors for postoperative aggravation of sexual function. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Tracheal stenosis due to cervicothoracic hyperlordosis in patients with cerebral palsy treated with posterior spinal fusion: a report of the first two cases.

BACKGROUND: Spinal deformity is frequently identified in patients with cerebral palsy (CP). As it progresses, tracheal stenosis often develops due to compression between the innominate artery and anteriorly deviated vertebrae at the apex of the cervicothoracic hyperlordosis. However, the treatment strategy for tracheal stenosis complicated by spinal deformity in patients with CP remains unknown. CASE PRESENTATION: This study reports two cases: a 19-year-old girl (case 1) and a 17-year-old girl (case 2), both with CP at Gross Motor Function Classification System V. Both patients experienced acute oxygen desaturation twice within the past year of their first visit to our department. X-ray and computed tomography revealed severe scoliosis and cervicothoracic hyperlordosis causing tracheal stenosis at T2 in case 1 and at T3-T4 in case 2, suggesting that their acute oxygen desaturation had been caused by impaired airway clearance due to tracheal stenosis. After preoperative halo traction for three weeks, both patients underwent posterior spinal fusion from C7 to L5 with Ponte osteotomy and sublaminar taping at the proximal thoracic region to correct cervicothoracic hyperlordosis and thoracolumbar scoliosis simultaneously. Postoperative X-ray and computed tomography revealed that the tracheal stenosis improved in parallel with the correction of cervicothoracic hyperlordosis. Case 1 did not develop respiratory failure 1.5 years after surgery. Case 2 required gastrostomy postoperatively due to severe aspiration pneumonia. However, she developed no respiratory failure related to impaired airway clearance at one-year follow-up. CONCLUSIONS: We present the first two cases of CP that developed tracheal stenosis caused by cervicothoracic hyperlordosis concomitant with progressive scoliosis and were successfully treated by posterior spinal fusion from C7 to L5. This enabled us to relieve tracheal stenosis and correct the spinal deformity at the same time. Surgeons must be aware of the possibility of coexisting tracheal stenosis in treating spinal deformity in patients with neurological impairment because the surgical strategy can vary in the presence of tracheal stenosis. This study demonstrated that some patients with CP with acquired tracheal stenosis can be treated with spinal surgery.

Associations between curve severity and revised Scoliosis Research Society-22 and scoliosis Japanese Questionnaire-27 scores in female patients with adolescent idiopathic scoliosis: a multicenter, cross-sectional study.

BACKGROUND: Patient-reported outcome measures are widely utilized to assess health-related quality of life (HRQOL) in patients with adolescent idiopathic scoliosis (AIS). However, the association between HRQOL and curve severity is mostly unknown. The aim of this study is to clarify the association between HRQOL and curve severity, and to determine the optimal cutoff values of patient-reported outcomes for major curve severity in female patients with AIS. METHODS: Female patients with AIS treated conservatively were recruited. The patients' HRQOL outcomes were examined using the revised Scoliosis Research Society-22 (SRS-22r) and the Scoliosis Japanese Questionnaire-27 (SJ-27). The correlations of the SRS-22r and SJ-27 scores with the major Cobb angle were assessed using Spearman's correlation coefficient analysis. The association between HRQOL issues in the SJ-27 and the major Cobb angle was evaluated by calculating Akaike's Information Criterion (AIC). Furthermore, the optimal cutoff values of the SRS-22r and SJ-27 scores for the major Cobb angle were determined by AIC analysis. RESULTS: The study cohort comprised 306 female patients with AIS. The SRS-22r and SJ-27 scores were significantly correlated with the major Cobb angle. Questions in the SJ-27 regarding discomfort when wearing clothes showed a lower AIC value in patients with severe scoliosis. The optimal cutoff values were a SRS-22r score of 3.2 for the discrimination of severe scoliosis (Cobb angle ≥48°), and a SJ-27 score of 32 for the discrimination of moderate scoliosis (Cobb angle ≥33°). CONCLUSION: Discomfort when wearing clothes was the most important HRQOL problem caused by severe scoliosis. The SRS-22r and SJ-27 scores are useful for the discrimination of clinical status in female patients with severe scoliosis or moderate scoliosis.

Comparison between microendoscopic laminectomy and open posterior decompression surgery for single-level lumbar spinal stenosis: a multicenter retrospective cohort study.

BACKGROUND: Microendoscopic laminectomy (MEL), in which a 16-mm tubular retractor with an internal scope is used, has shown excellent surgical results for patients with lumbar spinal canal stenosis. However, no reports have directly compared MEL with open laminectomy. This study aimed to elucidate patient-reported outcomes (PROs) and perioperative complications in patients undergoing MEL versus open laminectomy. METHODS: This is a multicenter retrospective cohort study of prospectively registered patients who underwent lumbar spinal surgery at one of the six high-volume spine centers between April 2017 and September 2018. A total of 258 patients who underwent single posterior lumbar decompression at L4/L5 were enrolled in the study. With regard to demographic data, we prospectively used chart sheets to evaluate the diagnosis, operative procedure, operation time, estimated blood loss, and complications. The follow-up period was 1-year. PROs included a numerical rating scale (NRS) for lower back pain and leg pain, the Oswestry Disability Index (ODI), EuroQol 5 Dimension (EQ-5D), and patient satisfaction with the treatment. RESULTS: Of the 258 patients enrolled, 252 (97%) completed the 1-year follow-up. Of the 252, 130 underwent MEL (MEL group) and 122 underwent open decompression (open group). The MEL group required a significantly shorter operating time and sustained lesser intraoperative blood loss compared with the open group. The MEL group showed shorter length of postoperative hospitalization than the open group. The overall complication rate was similar (8.2% in the MEL group versus 7.7% in the open group), and the revision rate did not significantly differ. As for PROs, both preoperative and postoperative values did not significantly differ between the two groups. However, the satisfaction rate was higher in the MEL group (74%) than in the open group (53%) (p = 0.02). CONCLUSIONS: MEL required a significantly shorter operating time and resulted in lesser intraoperative blood loss compared with laminectomy. Postoperative PROs and complication rates were not significantly different between the procedures, although MEL demonstrated a better satisfaction rate.

Anatomical study of cervical intervertebral foramen in patients with cervical spondylotic radiculopathy.

PURPOSE: To determine the underlying anatomical characteristics in patients with cervical spondylotic radiculopathy (CSR) by comparing those of surgically treated CSR patients with those of healthy subjects. METHODS: Computed tomography (CT) scans of the cervical spine in 42 patients who underwent decompression surgery for CSR were investigated. As a control group, 42 age- and sex-matched healthy subjects were randomly selected from the 1272 subjects who underwent CT examinations of the entire spine as their routine medical check-up. Image measurements included C2-7 sagittal Cobb angle, spinal canal diameters, and angles of the nerve root groove at each level from C3 to C7, and the size of the intervertebral foramen and the size of osteophytes at each level from C3/4 to C7/T1. As for the frequency of osteophytes at the surgical level, we compared the operated and nonoperated intervertebral foramina among the CSR patients, and all other parameters were compared with the corresponding segments in the control group. RESULTS: Forty-eight intervertebral segments were surgically treated in the CSR group. There was a higher incidence of osteophytes in the operated foramen (70.8%) than in the nonoperated foramen (28.2%, p < 0.01) in the patients with CSR. The anteroposterior diameter (width) of the foramen was significantly smaller at all levels in the CSR patients, whereas the height of the foramen did not significantly differ between the two groups. CONCLUSION: It can be speculated that the width of the intervertebral foramen (developmental factor) and the formation of osteophytes (spondylotic factor) were related to the onset of the CSR.

Effect of Spinal Alignment Changes on Lower Back Pain in Patients Treated with Total Hip Arthroplasty for Hip Osteoarthritis.

Background and objectives: The influence of changes in spinal alignment after total hip arthroplasty (THA) on improvement in lower back pain (LBP) remains controversial. To evaluate how changes in spinal malalignment correlate with improvement in preoperative LBP in patients who underwent THA for hip osteoarthritis. Materials and Methods: From November 2015 to January 2017, 104 consecutive patients who underwent unilateral THA were prospectively registered. Whole spine X-rays and patient-reported outcomes (PROs) were obtained preoperatively and 12 months postoperatively. The PROs used were the Numerical Rating Scale (NRS) for back pain, EuroQol 5 Dimension, and Short Form-12. Results: Seventy-four (71%) patients with complete data were eligible for the analysis. The sagittal parameters changed slightly but significantly. Coronal alignment significantly improved. Twenty-six (37%) patients had LBP preoperatively. These patients had smaller lumbar lordosis (LL), larger PT, and larger PI minus LL than the patients without LBP. Fourteen (54%) of the 26 patients with preoperative LBP showed pain improvement, but there were no significant differences in the radiographic parameters. Conclusions: Although preoperative LBP was likely to be resolved after THA, there were no significant correlations between alignment changes and LBP improvement. The cause of LBP in patients with hip osteoarthritis (OA) patients might be multifactorial.

Associated factors for and progression rate of sacroiliac joint degeneration in subjects undergoing comprehensive medical checkups.

PURPOSE: Associated factors for and the natural course of sacroiliac (SI) joint degeneration in the normal population are unknown. The purpose of this study was to determine associated factors for and the progression rate of SI joint degeneration. METHODS: We enrolled 553 healthy middle-aged subjects who underwent the first and second comprehensive health screening at an interval of 5.9 years (range 3.0-10.7 years). The medical checkup included blood tests and whole-body computed tomography. We investigated associated factors of SI joint degeneration, the relationship of the laterality of degeneration between the SI and L4/5 facet joint, L5/S facet joint, and the natural course of SI joint degeneration over time. RESULTS: At the first checkup, 70 subjects (12.7%) showed substantial degeneration (type 2 or 3) of the SI joints. Multivariate analysis revealed that female sex; pubic symphysis degeneration, L4/5, and L5/S facet joint degeneration; high body mass index; and several blood parameters were associated factors for SI joint degeneration. Laterality of SI joint degeneration was significantly more frequent than that of L4/5 or L5/S facet joint degeneration. Kaplan-Meier survival analysis revealed that the progression rates of SI joint degeneration from type 0 (no degeneration) or type 1 (slight degeneration) to substantial degeneration amounted to 3.4% and 35.5% after 10 years, respectively. CONCLUSION: We found substantial SI joint degeneration in 12.7% of healthy middle-aged subjects and considered it to be part of the normal aging process. There may be individual factors associated with its occurrence. These slides can be retrieved under Electronic Supplementary Material.

Comparison of microendoscopic selective laminectomy versus conventional laminoplasty in patients with degenerative cervcical myelopathy: a minimum 2-year follow-up study.

BACKGROUND: Although microendoscopic partial laminectomy for patients with degenerative cervical myelopathy (DCM) has been reported and demonstrated good results, a detailed comparison of its mid-term surgical results with those of laminoplasty (LP) has not been reported. The aim of this study was to compare the surgical outcomes, complications, and imaging parameters of cervical microendoscopic interlaminar decompression (CMID) via a midline approach versus conventional laminoplasty, with a minimum follow-up period of 2 years. METHODS: Two hundred and fifty-four patients who underwent either LP or CMID for DCM between May 2008 and April 2015 were enrolled. All patients routinely underwent LP (C3-6 or C3-7) before December 2011, whereas CMID was performed at the one or two affected level(s) only in patients with single- or two-level spinal cord compression after 2012. Surgical procedure (CMID): For single-level patients (e.g., C5-6), partial laminectomy of C5 and C6 was performed under a microendoscope. For two-level patients (e.g., C5-6-7), decompression was completed by performing a C6 laminectomy. We compared surgical outcomes and radiographic parameters between the CMID and LP groups. RESULTS: Of the 232 patients followed up for > 2 years, 87 patients with single- or two-level spinal cord compression, 46 that underwent CMID, and 41 that underwent LP were identified. There were no differences in the baseline demographic data of the patients between the groups. CMID showed better outcomes in terms of postoperative axial pain and quality of life, although both procedures showed good neurological improvement. Two and one patient complained of C5 palsy and hematoma, respectively, only in the LP group. The postoperative range of motion was worse and the degree of postoperative posterior spinal cord shift was larger in the LP group. CONCLUSION: Selective decompression by CMID demonstrated surgical outcomes equivalent to those of conventional LP, which raises a question regarding the requirement of extensive posterior spinal cord shift in such patients. Although the indications of CMID are limited and comparison with anterior surgery is mandatory, it can be a minimally invasive procedure for DCM. .

Chd7 Collaborates with Sox2 to Regulate Activation of Oligodendrocyte Precursor Cells after Spinal Cord Injury.

Oligodendrocyte precursor cells (OPCs) act as a reservoir of new oligodendrocytes (OLs) in homeostatic and pathological conditions. OPCs are activated in response to injury to generate myelinating OLs, but the underlying mechanisms remain poorly understood. Here, we show that chromodomain helicase DNA binding protein 7 (Chd7) regulates OPC activation after spinal cord injury (SCI). Chd7 is expressed in OPCs in the adult spinal cord and its expression is upregulated with a concomitant increase in Sox2 expression after SCI. OPC-specific ablation of Chd7 in injured mice leads to reduced OPC proliferation, the loss of OPC identity, and impaired OPC differentiation. Ablation of Chd7 or Sox2 in cultured OPCs shows similar phenotypes to those observed in Chd7 knock-out mice. Chd7 and Sox2 form a complex in OPCs and bind to the promoters or enhancers of the regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) genes, thereby inducing their expression. The expression of Rgcc and PKCθ is reduced in the OPCs of the injured Chd7 knock-out mice. In cultured OPCs, overexpression and knock-down of Rgcc or PKCθ promote and suppress OPC proliferation, respectively. Furthermore, overexpression of both Rgcc and PKCθ rescues the Chd7 deletion phenotypes. Chd7 is thus a key regulator of OPC activation, in which it cooperates with Sox2 and acts via direct induction of Rgcc and PKCθ expression.SIGNIFICANCE STATEMENT Spinal cord injury (SCI) leads to oligodendrocyte (OL) loss and demyelination, along with neuronal death, resulting in impairment of motor or sensory functions. Oligodendrocyte precursor cells (OPCs) activated in response to injury are potential sources of OL replacement and are thought to contribute to remyelination and functional recovery after SCI. However, the molecular mechanisms underlying OPC activation, especially its epigenetic regulation, remain largely unclear. We demonstrate here that the chromatin remodeler chromodomain helicase DNA binding protein 7 (Chd7) regulates the proliferation and identity of OPCs after SCI. We have further identified regulator of cell cycle (Rgcc) and protein kinase Cθ (PKCθ) as novel targets of Chd7 for OPC activation.

Reliability and validity of a novel quality of life questionnaire for female patients with adolescent idiopathic scoliosis: Scoliosis Japanese Questionnaire-27: a multicenter, cross-sectional study.

BACKGROUND: A progressive deformity associated with adolescent idiopathic scoliosis (AIS) negatively affects a patient's health-related quality of life (HRQOL). Although the Scoliosis Research Society-22 (SRS-22) is the standard measurement tool for assessing HRQOL in patients with AIS, it is partially suboptimal for evaluating HRQOL in Japanese patients with AIS because of cultural differences. The purpose of this study was to develop a novel patient-reported outcome measure for Japanese female patients with AIS and to evaluate the reliability and validity of this questionnaire in comparison with the SRS-22 tool. METHODS: We developed 27 questions based on the psychosocial problems in the daily life of young female patients with AIS in Japan, the Scoliosis Japanese Questionnaire-27 (SJ-27). To evaluate its reliability, the internal consistency was assessed using Cronbach's alpha coefficient. Concurrent validity was evaluated using Spearman's correlation coefficient between the SJ-27 and the SRS-22. To investigate the construct validity of the SJ-27, the correlation between the SJ-27 questions was assessed using Akaike's information criterion (AIC). RESULTS: We analyzed 384 female patients with AIS. Cronbach's alpha coefficients were 0.914 and 0.829 for the SJ-27 and the SRS-22, respectively. Spearman's correlation coefficient between the SJ-27 and the SRS-22 was 0.692 (p < 0.001). The AIC analysis indicated that the SJ-27 items are divided into five domains, indicating that the SJ-27 covered a wide range of health-related problems among female patients with AIS. CONCLUSIONS: The results suggest that the SJ-27 is a reliable and valid patient-reported outcome measure for evaluating HRQOL in female patients with AIS in Japan.

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation.

Oligodendrocyte progenitor cells (OPCs) undergo marked morphological changes to become mature oligodendrocytes, but the metabolic resources for this process have not been fully elucidated. Although lactate, a metabolic derivative of glycogen, has been reported to be consumed in oligodendrocytes as a metabolite, and to ameliorate hypomyelination induced by low glucose conditions, it is not clear about the direct contribution of lactate to cell cycling and differentiation of OPCs, and the source of lactate for remyelination. Therefore, we evaluated the effect of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), an inhibitor of the glycogen catabolic enzyme glycogen phosphorylase, in a mouse cuprizone model. Cuprizone induced demyelination in the corpus callosum and remyelination occurred after cuprizone treatment ceased. This remyelination was inhibited by the administration of DAB. To further examine whether lactate affects proliferation or differentiation of OPCs, we cultured mouse primary OPC-rich cells and analyzed the effect of lactate. Lactate rescued the slowed cell cycling induced by 0.4 mM glucose, as assessed by the BrdU-positive cell ratio. Lactate also promoted OPC differentiation detected by monitoring the mature oligodendrocyte marker myelin basic protein, in the presence of both 36.6 mM and 0.4 mM glucose. Furthermore, these lactate-mediated effects were suppressed by the reported monocarboxylate transporter inhibitor, α-cyano-4-hydroxy-cinnamate. These results suggest that lactate directly promotes the cell cycling rate and differentiation of OPCs, and that glycogen, one of the sources of lactate, contributes to remyelination in vivo. J. Cell. Physiol. 232: 986-995, 2017. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

The crucial role of Erk2 in demyelinating inflammation in the central nervous system.

BACKGROUND: Brain inflammation is a crucial component of demyelinating diseases such as multiple sclerosis. Although the initiation of inflammatory processes by the production of cytokines and chemokines by immune cells is well characterized, the processes of inflammatory aggravation of demyelinating diseases remain obscure. Here, we examined the contribution of Erk2, one of the isoforms of the extracellular signal-regulated kinase, to demyelinating inflammation. METHODS: We used the cuprizone-induced demyelinating mouse model. To examine the role of Erk2, we used Nestin-cre-driven Erk2-deficient mice. We also established primary culture of microglia or astrocytes in order to reveal the crosstalk between two cell types and to determine the downstream cascades of Erk2 in astrocytes. RESULTS: First, we found that Erk is especially activated in astrocytes within the corpus callosum before the peak of demyelination (at 4 weeks after the start of cuprizone feeding). Then, we found that in our model, genetic ablation of Erk2 from neural cells markedly preserved myelin structure and motor function as measured by the rota-rod test. While the initial activation of microglia was not altered in Erk2-deficient mice, these mice showed reduced expression of inflammatory mediators at 3-4 model weeks. Furthermore, the subsequent inflammatory glial responses, characterized by accumulation of microglia and reactive astrocytes, were significantly attenuated in Erk2-deficient mice. These data indicate that Erk2 in astrocytes is involved in augmentation of inflammation and gliosis. We also found that activated, cultured microglia could induce Erk2 activation in cultured astrocytes and subsequent production of inflammatory mediators such as Ccl-2. CONCLUSIONS: Our results suggest that Erk2 activation in astrocytes plays a crucial role in aggravating demyelinating inflammation by inducing inflammatory mediators and gliosis. Thus, therapies targeting Erk2 function in glial cells may be a promising approach to the treatment of distinct demyelinating diseases.