Anti-Stress and Anti-ROS Effects of MnOx-Functionalized Thermosensitive Nanohydrogel Protect BMSCs for Intervertebral Disc Degeneration Repair.

Stem cell transplantation has been proven to be a promising strategy for intervertebral disc degeneration (IDD) repair. However, replicative senescence of bone marrow-derived mesenchymal stem cells (BMSCs), shear damage during direct injection, mechanical stress, and the reactive oxygen species (ROS)-rich microenvironment in degenerative intervertebral discs (IVDs) cause significant cellular damage and limit the therapeutic efficacy. Here, an injectable manganese oxide (MnOx)-functionalized thermosensitive nanohydrogel was proposed for BMSC transplantation for IDD therapy. The MnOx-functionalized thermosensitive nanohydrogel not only successfully protected BMSCs from shear force and mechanical stress before and after injection but also repaired the harsh high-ROS environment in degenerative IVDs, thus effectively increasing the viability of BMSCs and resident nucleus pulposus cells (NPCs). The MnOx-functionalized thermosensitive nanohydrogel provides mechanical protection for stem cells and helps to remove endogenous ROS, providing a promising stem cell delivery platform for the treatment of IDD. This article is protected by copyright. All rights reserved.

Risk Factors for Surgical Treatment of Lumbar Degenerative Disc Disease in Middle-aged and Older Women: A Prospective Case-Control Study of 2370 Subjects.

OBJECTIVE: Given the distinct physiological and societal traits between women and men, we propose that there are distinct risk factors for lumbar degenerative disc disease surgeries, including lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS), in middle-aged and older populations. However, few studies have focused on middle-aged and older women. This study aims to identify these risk factors specifically in this population. METHODS: In this case-control study, the study group comprised 1202 women aged ≥ 45 years who underwent operative treatment of lumbar degenerative disc disease (LDH, n = 825; LSS, n = 377), and the control group comprised 1168 women without lumbar disease who visited a health examination clinic during the same period. The study factors included demographics (age, body mass index [BMI], smoking, labor intensity, and genetic history), female-specific factors (menopausal status, number of deliveries, cesarean section, and simple hysterectomy), surgical history (number of abdominal surgeries, hip joint surgery, knee joint surgery, and thyroidectomy), and systemic diseases (hypercholesterolemia, hypertriglyceridemia, hyper-low-density lipoprotein cholesterolemia, hypertension, diabetes, cardiovascular disease, and cerebrovascular disease). Multivariate binary logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of associated factors. RESULTS: The risk factors for surgical treatment of LDH in middle-aged and older women included BMI (OR = 1.603), labor intensity (OR = 1.189), genetic history (OR = 2.212), number of deliveries (OR = 1.736), simple hysterectomy (OR = 2.511), hypertriglyceridemia (OR = 1.932), and hyper-low-density lipoprotein cholesterolemia (OR = 2.662). For surgical treatment of LSS, the risk factors were age (OR = 1.889), BMI (OR = 1.671), genetic history (OR = 2.134), number of deliveries (OR = 2.962), simple hysterectomy (OR = 1.968), knee joint surgery (OR = 2.527), hypertriglyceridemia (OR = 1.476), hyper-low-density lipoprotein cholesterolemia (OR = 2.413), and diabetes (OR = 1.643). Cerebrovascular disease was a protective factor against surgery for LDH (OR = 0.267). CONCLUSIONS: BMI, genetic history, number of deliveries, simple hysterectomy, hypertriglyceridemia, and hyper-low-density lipoprotein cholesterolemia were independent risk factors for surgical treatment of both LDH and LSS in middle-aged and older women. Two disparities were found: labor intensity was a risk factor for LDH patients, and knee joint surgery and diabetes were risk factors for LSS patients.

Impact of bilateral facet joint violation on radiographic degeneration of superior adjacent segments and clinical outcomes.

OBJECTIVE: Facet joint violation (FJV) is associated with postoperative low-back pain and is a confirmed risk factor for adjacent-segment degeneration, a long-term complication of lumbar fusion surgery. The authors' knowledge of its mechanisms comes from in vitro biomechanical research only; there is a lack of radiographic evidence of the effects of violation on the superior adjacent-segment facet joint, intervertebral disc, and other local radiographic parameters. Furthermore, any differences between unilateral and bilateral violation remain relatively unclear. The authors therefore aimed to explore the effects of nonviolation and unilateral and bilateral violation on radiographic degeneration of the facet joint and intervertebral disc at the fusion and superior adjacent segment. Patient-reported clinical outcomes were compared at the 2-year follow-up. METHODS: The authors retrospectively analyzed data from 148 patients with lumbar degenerative diseases who underwent single-segment minimally invasive transforaminal lumbar interbody fusion between 2016 and 2020. FJV and facet joint degeneration were evaluated and graded using Shah's method and Pathria's standard, respectively. Radiographic parameters, including disc height and intervertebral Cobb angle at the fusion and superior adjacent segment, were measured. Clinical outcomes were evaluated using visual analog scale (VAS) and Japanese Orthopaedic Association scores. RESULTS: Preoperative data were comparable among the 3 groups (nonviolation, unilateral violation, and bilateral violation) (p > 0.05). Patient-reported clinical outcomes were followed up for at least 2 years (average duration 28.17 ± 6.17 months). At the last follow-up, facet joint degeneration grades were sequentially increased in the nonviolation, unilateral violation, and bilateral violation groups (p = 0.006). The unilateral (2.45 ± 2.17 mm) and bilateral (2.70 ± 1.94 mm) violation groups had more severe losses of disc height in the superior adjacent segment than did the nonviolation group (1.31 ± 2.01 mm). The VAS low-back pain and Japanese Orthopaedic Association scores in the bilateral (2.57 ± 1.44 and 19.83 ± 2.84, respectively) and unilateral (2.26 ± 0.79 and 20.43 ± 3.85, respectively) violation groups were significantly worse than in the nonviolation group (1.69 ± 1.12 and 21.80 ± 3.36, respectively) (p < 0.05). By contrast, there were no significant between-group differences in disc height, intervertebral Cobb angle in the fusion segment, or VAS leg pain scores (p > 0.05). CONCLUSIONS: FJV was associated with postoperative low-back pain and worse functional outcomes. It also aggravated facet joint and intervertebral disc changes in the superior adjacent segment, especially when bilateral violation occurred; this may be part of the mechanisms of adjacent-segment degeneration.

A statistical symptomatic evaluation on SAPHO syndrome from 56 cases of confirmed diagnosis and 352 cases of non-SAPHO involvement.

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome. METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed. RESULT: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores. CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx.

To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (Col2a1-CreERT Piezo1flox/flox) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout (cDKO) mice (Col2a1-CreERT Piezo1flox/flox/Gpx4flox/flox). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

Comparison of Clinical and Radiographic Outcomes Between Transforaminal Endoscopic Lumbar Discectomy and Microdiscectomy: A Follow-up Exceeding 5 Years.

OBJECTIVE: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). METHODS: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients' clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. RESULTS: During a mean follow-up of 5.5 years (range, 5-7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. CONCLUSION: Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

Novel Modic grading scoring system and its clinical validation: a preliminary investigation.

PURPOSE: To propose a novel Modic grading scoring system and explore the relationship between the Modic grading score and disc degeneration, disc herniation, disc height, and clinical symptom scores. METHOD: In total, 194 patients were included in the study. The new Modic grading scoring system included four indicators: invaded vertebral height, invaded endplate length, endplate morphology, and grade of endplate defects. The severity of Modic changes was visually quantified by numerical scores, and the kappa value was used to verify the interobserver and intraobserver reliability. Spearman correlation analysis was used to explore the relationship between the Modic grading score and intervertebral disc degeneration, disc herniation, disc height, and clinical symptom scores. RESULTS: The interobserver and intraobserver reliability showed substantial to almost perfect agreement in the new Modic grading scoring system. The Modic grading score was positively correlated with intervertebral disc degeneration (r = 0.757, p < 0.001) and negatively correlated with the intervertebral disc height index (r = - 0.231, p < 0.001). There was no significant correlation between the Modic grading scoring system and disc herniation (r = 0.369, p = 0.249). Additionally, there was no significant correlation between the Modic grading score and the Japanese Orthopaedic Association score (r = - 0.349, p = 0.25), Oswestry Disability Index score (r = 0.246, p = 0.11), or visual analogue scale score (r = 0.315, p = 0.35). CONCLUSION: The new Modic grading scoring system had good interobserver and intraobserver reliability. The Modic grading score was positively correlated with intervertebral disc degeneration and negatively correlated with the intervertebral disc height.

Effect of Topical Nonsteroidal Anti-inflammatory Drugs Around the Incision on Postoperative Pain in Transforaminal Lumbar Interbody Fusion Surgery: A Double-blind Randomized Controlled Trial.

BACKGROUND: How to minimize postoperative pain following spinal surgery has been a great challenge. We hypothesized that topical nonsteroidal anti-inflammatory drugs (NSAIDs) around the incision could relieve postoperative pain following transforaminal lumbar interbody fusion (TLIF) surgery. OBJECTIVE: This study tested the effect of topical NSAIDs around the incision for pain management after TLIF surgery. STUDY DESIGN: A double-blind randomized controlled trial. SETTING: Qilu Hospital of Shandong University. METHODS: Eighty patients who underwent single-level TLIF surgery were randomized into 2 groups. The treatment group received postoperative topical NSAIDs around the incision. The control group received a postoperative topical placebo around the incision. All patients in both groups received postoperative patient-controlled analgesia (PCA) via an analgesia pump. The primary outcome measures were the amount of opioid consumption and pain measurement via the visual analog scale (VAS). The secondary outcome measures were the time of first analgesic demand, operation time, postoperative drain output, side effects of opioids, postoperative stay, and Oswestry Disability Index (ODI) score. RESULTS: The consumption of opioids in the treatment group was significantly less than in the control group at postoperative 12 hours, 12 to 24 hours, and 24 to 48 hours (P < 0.005). The VAS in the treatment group was significantly lower than those in the control group at all assessment times within 72 hours postoperative (P < 0.005). The time of first analgesic demand of PCA in the treatment group was significantly longer than that in the control group (P < 0.005). The side effects of opioids were significantly less in the treatment group than in the control group (P < 0.05). There was no significant difference in operation time, postoperative drain output, postoperative stay, and ODI between the 2 groups (P > 0.05). LIMITATIONS: This was a single-center study for single-level TLIF surgery. CONCLUSION: Postoperative topical NSAID around the incision is a highly effective and safe method for postoperative pain management following single-level TLIF surgery. In our study it reduced postoperative opioid requirements and prolonged the time of first analgesic demand with no increased side effects. KEY WORDS: Transforaminal lumbar interbody fusion, postoperative pain, NSAID, topical NSAID, nonsteroidal anti-inflammatory drug, loxoprofen.

Pentraxin 3 deficiency ameliorates the severity of osteoarthritis and alleviates inflammation.

BACKGROUND: Osteoarthritis is one of the most common degenerative joint disorders, characterized by articular cartilage breakdown, synovitis, osteophytes generation and subchondral bone sclerosis. Pentraxin 3 (PTX3) is a long pentraxin protein, secreted by immune cells, and PTX3 is identified to play a critical role in inflammation and macrophage polarization. However, the underlying mechanism of PTX3 in osteoarthritis under the circumstance of Ptx3-knockout (KO) mice model is still unknown. METHODS: Murine destabilization of the medial meniscus (DMM) OA model was created in Ptx3-knockout (KO) and wildtype mice, respectively. The degenerative status of cartilage was detected by Safranin O, H&E staining, immunohistochemistry (IHC) and micro-CT. OARSI scoring was employed to assess the proteoglycan of cartilage. Serum inflammatory cytokines were examined by ELISA and systematic macrophage polarization in spleen was analyzed by flow cytometry. RESULTS: Safranin O and H&E staining confirmed that the joint cartilage was mostly with reduced degeneration in both the senior KO mice and the DMM model generated from the KO mice, compared to the WT group. This is also supported by micro-CT examination and OARSI scoring. Immunohistochemistry illustrated an up-regulation of Aggrecan and Collagen 2 and down-regulation of ADAMTS-5 and MMP13 in KO mice in comparison with the WT mice. ELISA indicated a dramatical decrease in the serum levels of TNF-α and IL-6 in KO mice. Polarization of M2-like macrophages was observed in the KO group. CONCLUSION: Pentraxin 3 deficiency significantly ameliorated the severity of osteoarthritis by preventing cartilage degeneration and alleviated systematic inflammation by inducing M2 polarization.

Variants in the SOX9 transactivation middle domain induce axial skeleton dysplasia and scoliosis.

SOX9 is an essential transcriptional regulator of cartilage development and homeostasis. In humans, dysregulation of SOX9 is associated with a wide spectrum of skeletal disorders, including campomelic and acampomelic dysplasia, and scoliosis. The mechanism of how SOX9 variants contribute to the spectrum of axial skeletal disorders is not well understood. Here, we report four novel pathogenic variants of SOX9 identified in a large cohort of patients with congenital vertebral malformations. Three of these heterozygous variants are in the HMG and DIM domains, and for the first time, we report a pathogenic variant within the transactivation middle (TAM) domain of SOX9 . Probands with these variants exhibit variable skeletal dysplasia, ranging from isolated vertebral malformation to acampomelic dysplasia. We also generated a Sox9 hypomorphic mutant mouse model bearing a microdeletion within the TAM domain ( Sox9 Asp272del ). We demonstrated that disturbance of the TAM domain with missense mutation or microdeletion results in reduced protein stability but does not affect the transcriptional activity of SOX9. Homozygous Sox9 Asp272del mice exhibited axial skeletal dysplasia including kinked tails, ribcage anomalies, and scoliosis, recapitulating phenotypes observed in human, while heterozygous mutants display a milder phenotype. Analysis of primary chondrocytes and the intervertebral discs in Sox9 Asp272del mutant mice revealed dysregulation of a panel of genes with major contributions of the extracellular matrix, angiogenesis, and ossification-related processes. In summary, our work identified the first pathologic variant of SOX9 within the TAM domain and demonstrated that this variant is associated with reduced SOX9 protein stability. Our finding suggests that reduced SOX9 stability caused by variants in the TAM domain may be responsible for the milder forms of axial skeleton dysplasia in humans.

Safety and accuracy of cannulated pedicle screw placement in scoliosis surgery: a comparison of robotic-navigation, O-arm-based navigation, and freehand techniques.

PURPOSE: To compare the safety and accuracy of cannulated pedicle screw placement using a robotic-navigation technique, O-arm-based navigation technique, or freehand technique. METHODS: This study analyzed 106 consecutive patients who underwent scoliosis surgery. Thirty-two patients underwent robotic-navigation-assisted pedicle screw insertion (Group 1), 34 patients underwent O-arm-based navigation-guided pedicle screw insertion (Group 2), and 40 patients underwent freehand pedicle screw insertion (Group 3). The primary outcome measure was the accuracy of screw placement. Secondary outcome parameters included operation time, blood loss, radiation exposure, and postoperative stay. RESULTS: A total of 2035 cannulated pedicle screws were implanted in 106 patients. The accuracy rate of the first pedicle screw placement during operation was significantly greater in Group 1 (94.7%) than in Group 2 (89.2%; P < 0.001). The accuracy rate of pedicle screw placement postoperatively decreased in the order of Group 1 (96.7%) > Group 2 (93.0%) > Group 3 (80.4%; P < 0.01). There were no significant differences in blood loss or postoperative stay among the three groups (P > 0.05). The operation times of Group 1 and Group 2 were significantly longer than that of Group 3 (P < 0.05). CONCLUSION: The robotic-navigation and O-arm-based navigation techniques effectively increased the accuracy and safety of pedicle screw insertion alternative to the freehand technique in scoliosis surgery. Compared with the O-arm-based navigation technique, the robotic-navigation technique increases the mean operation time, but also increases the accuracy of pedicle screw placement. A three-dimensional scan after insertion of the K-wire may increase the accuracy of pedicle screw placement in the O-arm-based navigation technique.

Comparative study of preoperative sagittal alignment between patients with multisegment cervical ossification of the posterior longitudinal ligament and cervical spondylotic myelopathy.

BACKGROUND CONTEXT: Preoperative sagittal alignment is of great significance in the development of spinal deformities, degenerative diseases, preoperative planning, postoperative clinical evaluation, and functional recovery. However, few reports have focused on the difference in preoperative sagittal alignment between patients with ossification of the posterior longitudinal ligament (OPLL) and patients with cervical spondylotic myelopathy (CSM). PURPOSE: To compare preoperative sagittal alignment between patients with multisegment cervical OPLL and multilevel CSM. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: A total of 243 patients were included in this study. OUTCOME MEASURES: The outcome measures were the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score, number of hand actions in 10 seconds, hand-grip strength, C2 to C7 Cobb angle, C2 to C5 Cobb angle, C5 to C7 Cobb angle, C2 to C7 sagittal vertical axis, C7 slope, T1 slope, K-line, K-line tilt, and range of motion (ROM). METHODS: The outcome measures were calculated in the OPLL group and CSM group and the data were analyzed using the unpaired t-test, χ² test, and one-way analysis of variance. RESULTS: A total of 243 patients (136 men, 107 women; mean age, 59.1±10.6 years) underwent surgical treatment from September 2013 to December 2021. In total, 123 patients were diagnosed with multisegment cervical OPLL, including continuous type (n=39), segmental type (n=38), and mixed type (n=46). The remaining 120 patients had multisegment CSM. The disease course in the OPLL group was significantly shorter than that in the CSM group (p<.05). Among the above preoperative measurements, the JOA score, number of hand actions in 10 seconds, hand-grip strength, and VAS score were not significantly different between the two groups (p>.05). The C2 to C7 Cobb angle was significantly larger in the OPLL than CSM group (17.7°±9.2° and 14.9°±9.3°, respectively; p< .05), as was the C5 to C7 Cobb angle (10.0°±6.3° and 7.5°±6.1°, respectively; p<.05). The ROM was significantly smaller in the OPLL than CSM group (33.1°±8.1° and 40.1°±10.9°, respectively; p<.001). Within the OPLL group, the ROM was significantly smaller in the continuous type than in the segmental type (p<.05). CONCLUSION: Patients with multisegment cervical OPLL have greater lordotic preoperative sagittal alignment and smaller preoperative ROM than patients with CSM.

Anterior cervical tunnectomy and fusion (ACTF): a novel technique for cervical canal decompression.

OBJECTIVE: To describe a novel surgical technique note coined as anterior cervical tunnectomy and fusion (ACTF) which applying on removal of posterior vertebral bony protrusions or soft extrusions. METHODS: Total twenty-three patients from January 2016 to January 2021 who experienced with spinal cord compression and performed by ACTF were retrospectively reviewed. Herein, relevant information including patient's gender, age, BMI, intraoperative time, intraoperative blood loss, postoperative complications and postoperative hospitalized stay were collected. Furthermore, JOA and VAS score were both collected. Moreover, imaging parameters were measured and calculated on radiographs. Correlated data were analyzed by t test. Significance was considered when P < 0.05. RESULTS: All patients in this study were validated with favorable outcomes and none of postoperative complications. The Nurick grade of patients dramatically deceased postoperation (P < 0.001). And postoperative VAS score of patients (P < 0.001), as well as JOA score (P < 0.001), was given dramatical significance comparing to preoperation. Furthermore, occupying rate (OR) (P < 0.001) was obviously reduced while space available cord (SAC) (P < 0.001) and diameter of spinal cord (P < 0.001) was significantly increased postoperation. Meanwhile, disc height of involved segment, C2-7 SVA, and C2-C7 Cobb angle were measured on sagittal plane of lateral radiograph. Postoperative disc height of involved segment (P < 0.001) significantly elevated comparing to preoperation. However, there were no significance on C2-7 SVA (P = 0.460) and C2-C7 Cobb angle (P = 0.097). CONCLUSIONS: The novel surgical technique coined by ACTF is a practicable approach during taking charge of bony and soft narrowing behind vertebral space.

Retrospective Analysis of Associated Anomalies in 636 Patients with Operatively Treated Congenital Scoliosis.

BACKGROUND: Congenital scoliosis is frequently associated with anomalies in multiple organ systems. However, the prevalence and distribution of associated anomalies remain unclear, and there is a large amount of variation in data among different studies. METHODS: Six hundred and thirty-six Chinese patients who had undergone scoliosis correction surgery at Peking Union Medical College Hospital from January 2012 to July 2019 were recruited, as a part of the Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study. The medical data for each subject were collected and analyzed. RESULTS: The mean age (and standard deviation) at the time of presentation for scoliosis was 6.4 ± 6.3 years, and the mean Cobb angle of the major curve was 60.8° ± 26.5°. Intraspinal abnormalities were found in 186 (30.3%) of 614 patients, with diastematomyelia being the most common anomaly (59.1%; 110 of 186). The prevalence of intraspinal abnormalities was remarkably higher in patients with failure of segmentation and mixed deformities than in patients with failure of formation (p < 0.001). Patients with intraspinal anomalies showed more severe deformities, including larger Cobb angles of the major curve (p < 0.001). We also demonstrated that cardiac anomalies were associated with remarkably worse pulmonary function, i.e., lower forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Additionally, we identified associations among different concomitant malformations. We found that patients with musculoskeletal anomalies of types other than intraspinal and maxillofacial were 9.2 times more likely to have additional maxillofacial anomalies. CONCLUSIONS: In our cohort, comorbidities associated with congenital scoliosis occurred at a rate of 55%. To our knowledge, our study is the first to show that patients with congenital scoliosis and cardiac anomalies have reduced pulmonary function, as demonstrated by lower FEV1, FVC, and PEF. Moreover, the potential associations among concomitant anomalies revealed the importance of a comprehensive preoperative evaluation scheme. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

How Sagittal Spinal Parameters Predict Anterolateral Spinal Ossification Severity: A Study Based on CT Classification.

STUDY DESIGN: Retrospective observational study. OBJECTIVE: The purpose of this study was to establish a CT classification system of anterolateral spinal ossification and analyze the effects of sagittal spinal parameters on ossification. SUMMARY OF BACKGROUND DATA: Patients with diffuse idiopathic skeletal hyperostosis often present with anterolateral ossification of the spine. Few reports consider anterolateral spinal ossification at each spinal level or explore the influence of sagittal alignment. MATERIALS AND METHOD: One hundred and twenty patients (79 males and 41 females) over 60 years old who underwent whole spinal CT scans from October 2018 to November 2021 were analyzed. Volume rendering technique images were used to assess the degree of anterolateral spinal ossification in each intervertebral space, and a classification system was established. Sagittal parameters, such as thoracic kyphosis, lumbar lordosis (LL), cervical lordosis, sacral slope, and thoracolumbar junction angle of the patients were measured. Multifactor stepwise linear regression analysis and ordered logistic regression analysis were used to study the effects of the sagittal parameters on ossification grades. RESULTS: The median age of the study population was 67 years (63-72 IQR). The new classification system classifies the severity of anterolateral spinal ossification in each intervertebral space into grades 0 to 3 with an intra-observer intraclass correlation coefficient value of 0.909 and inter-observer intraclass correlation coefficient value of 0.900. Multivariate stepwise linear regression analysis showed that age (OR=1.30, P <0.001), weight (OR=1.23, P =0.013), and cervical lordosis (OR=1.19, P <0.001) were significantly correlated with total ossification grade. Multifactor ordered logistic regression analysis showed that there was a statistically significant correlation between cervical lordosis and the ossification grades of each intervertebral space of T1~T4 ( P ≤0.005), between thoracic kyphosis and each intervertebral space in T4~T12 ( P ≤0.019), and between thoracolumbar junction angle and each intervertebral space in T10~L3 ( P ≤0.025). LL was significantly and positively correlated with the ossification grades of each intervertebral space in T7~T11 ( P ≤0.041). LL and sacral slope were significantly negatively correlated with the ossification grades of each intervertebral space in L3~S1 ( P ≤0.047). CONCLUSION: Our new classification scheme demonstrated good accuracy and reliability for the evaluation of the severity of anterolateral spinal ossification. The effect of sagittal parameters on anterolateral spinal ossification was position-specific. The greater the kyphosis or the smaller the lordosis of a spinal region, the more severe the degree of ossification in the corresponding region. LEVEL OF EVIDENCE: 3.

Sacroiliac joint degeneration in degenerative lumbar spondylolisthesis and related risk factors: a retrospective study.

OBJECTIVE: This study was performed to evaluate the degree of radiological sacroiliac joint (SIJ) degeneration in patients with degenerative lumbar spondylolisthesis (DLS). The related risk factors for SIJ degeneration were also investigated. METHODS: We retrospectively analyzed the lumbar and pelvic computed tomography (CT) scans of 303 patients with DLS admitted from January 2018 to December 2021. One hundred and fifty-six age-, gender-, and body mass index-matched patients without lumbar anomality who underwent lower abdominal or pelvic computed tomography scans were included in the control group. Sagittal parameters were measured on full-length lateral radiographs. Two protocols (Backlund's grade and Eno's classification) were used to assess SIJ degeneration. Univariate analysis and bivariate and multivariate regression analysis were performed to identify the factors affecting SIJ degeneration in patients with DLS. RESULTS: According to Backlund's grade and Eno's classification, SIJ degeneration was more severe in the DLS group than in the control group (P < 0.001). Multi-segment degenerative changes (P = 0.032), two-level DLS (P = 0.033), a history of hysterectomy (P < 0.001), lower extremity pain (P = 0.016), and pelvic pain (P = 0.013) were associated with more significant SIJ degeneration as assessed by Backlund's grade. The results of Pearson's correlation analysis showed positive correlation between the sagittal vertical axis and SIJ degeneration (r = 0.232, P = 0.009). The multivariate linear regression analysis showed that a history of hysterectomy was significantly correlated with SIJ degeneration in patients with DLS (r = 1.951, P = 0.008). CONCLUSIONS: SIJ degeneration was more severe in patients with than without DLS. We should take SIJ degeneration into consideration when diagnosing and treating DLS especially those who had undergone previous hysterectomy or showed sagittal malalignment.

Therapeutic management and amputation options in a long time delayed blunt popliteal artery injury.

PURPOSE: To report the experience of treatment on blunt traumatic popliteal artery injury (PAI) combined orthopedic injuries and determine the amputation-associated factors. METHODS: From January 2008 to December 2019, 55 patients in level I trauma center with traumatic blunt PAI were retrospectively reviewed. Variables were retrospectively collected and statistically analyzed. Patients with PAI with limb selvage, primary amputation, and secondary amputation were retrospectively grouped and compared. RESULTS: A total of 55 patients with a median age of 41.4 years (range 18-70), of which 45 were males (81.8%) and 10 were females (18.2%), were enrolled. The overall amputation rate was 36.4% because 88.6% of patients faced more than 6 h of delay before treatment. The average injury severe score (ISS) and abbreviated injury score (AIS) were 10.4 (range 9-34) and 8.2 (range 5-16), respectively. Multivariate regression analysis showed that the number of hospitalization days was a significantly related factor to amputation. After a median follow-up of 56 months (range 12-132), no death, another limb loss, or claudication was found in all patients. CONCLUSIONS: Patients with PAI are commonly accompanied by multiple injuries that increase the risk of amputation; therefore, timely treatments are urgently required. Reducing the severity of ischemia by fasciotomy, not losing time by performing preoperative imaging or diagnostic tests, and repairing the associated venous injury can help to optimize the rates of limb salvage. However, impact factors, such as the gender and age of the patient, injured mechanisms, concomitant injuries, AIS, ISS, and surgical times, are not associated with the outcomes of amputation. Nonetheless, endeavors to salvage the limbs as far as possible should be made.

Co-exposure to nanoplastics and acetaminophen causes skeletal dysplasia and behavioral abnormalities in zebrafish.

Nanoplastics (NPs) and acetaminophen (APAP) are thought to be common contaminants and are invariably detected in the environment. Despite the increasing awareness of their toxicity to humans and animals, the embryonic toxicity, skeletal development toxicity, and mechanism of action of their combined exposure have not been clarified. This study was performed to investigate whether combined exposure to NPs and APAP induces abnormal embryonic and skeletal development in zebrafish and to explore the potential toxicological mechanisms. All zebrafish juveniles in the high-concentration compound exposure group showed some abnormal phenomena such as pericardial edema, spinal curvature, cartilage developmental abnormality and melanin inhibition together with a significant downward trend in body length. Behavioral data also implicated that the exposure of APAP alone, as well as the co-exposure of NPs and APAP, caused a depression in the total distance, swimming speed and the maximum acceleration. Furthermore, real-time polymerase chain reaction analysis showed that compared with exposure alone, the expression level of genes related to osteogenesis, runx2a, runx2b, Sp7, bmp2b and shh was significantly reduced with compound exposure. These results suggest that the compound exposure of NPs and APAP has adverse impacts on zebrafish embryonic development and skeletal growth.

Comparison of Clinical Outcomes of Cervical Laminoplasty for Cervical Spondylotic Myelopathy: Double-Door With Lamina Staple, Single-Door With Miniplate, and Double-Door With Spacer-A 2-Year Follow-Up Study.

BACKGROUND: There were few studies to compare the outcomes of different types of cervical laminoplasties. OBJECTIVE: To compare the clinical outcomes of double-door cervical laminoplasty with lamina staple (double-door staple), single-door cervical laminoplasty with miniplate (single-door miniplate), and double-door cervical laminoplasty with spacer (double-door spacer). METHODS: The study involved 166 patients with cervical spondylotic myelopathy (CSM). Fifty-two patients underwent double-door staple, 63 patients underwent single-door miniplate, and 51 patients underwent double-door spacer. The clinical outcomes were measured. RESULTS: There was no significant difference in Japanese Orthopedic Association score among the 3 groups ( P > .05). The operation time was significantly shorter in double-door staple and single-door miniplate groups than in the double-door spacer group ( P < .005). The estimated blood loss was significantly more in the single-door miniplate group than in double-door staple and double-door spacer groups ( P < .005). The expansion ratio of cervical intraspinal cross-sectional area decreased in the order of double-door staple > double-door spacer > single-door miniplate. There were no significant differences in the expansion ratio of dural sac cross-sectional area among the 3 groups. CONCLUSION: Double-door staple, double-door spacer, and single-door miniplate can achieve favorable clinical outcomes for CSM. The blood loss of double-door staple is less than that of single-door miniplate, and the operation time of double-door staple is shorter than that of double-door spacer. The mean expansion ratio of cervical intraspinal cross-sectional area decreased in the order of double-door staple > double-door spacer > single-door miniplate. Overall, double-door staple is a safe and innovative alternative choice for treatment of CSM.

Corrigendum to "Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration" [Bioact. Mater. 23 (2023) 247-260].

[This corrects the article DOI: 10.1016/j.bioactmat.2022.10.019.].