Bone Marrow Aspirate Concentrate Combined with Ultra-Purified Alginate Bioresorbable Gel Enhances Intervertebral Disc Repair in a Canine Model: A Preclinical Proof-of-Concept Study.

Although discectomy is commonly performed for lumbar intervertebral disc (IVD) herniation, the capacity for tissue repair after surgery is limited, resulting in residual lower back pain, recurrence of IVD herniation, and progression of IVD degeneration. Cell-based therapies, as one-step procedures, are desirable for enhancing IVD repair. This study aimed to investigate the therapeutic efficacy of a combination of newly developed ultra-purified alginate (UPAL) gel and bone marrow aspirate concentrate (BMAC) implantation for IVD repair after discectomy. Prior to an in vivo study, the cell concentration abilities of three commercially available preparation kits for creating the BMAC were compared by measuring the number of bone marrow mesenchymal stem cells harvested from the bone marrow of rabbits. Subsequently, canine-derived BMAC was tested in a canine model using a kit which had the highest concentration rate. At 24 weeks after implantation, we evaluated the changes in the magnetic resonance imaging (MRI) signals as well as histological degeneration grade and immunohistochemical analysis results for type II and type I collagen-positive cells in the treated IVDs. In all quantitative evaluations, such as MRI and histological and immunohistochemical analyses of IVD degeneration, BMAC-UPAL implantation significantly suppressed the progression of IVD degeneration compared to discectomy and UPAL alone. This preclinical proof-of-concept study demonstrated the potential efficacy of BMAC-UPAL gel as a therapeutic strategy for implementation after discectomy, which was superior to UPAL and discectomy alone in terms of tissue repair and regenerative potential.

Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.

INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.

Deep learning-based detection of lumbar spinal canal stenosis using convolutional neural networks.

BACKGROUND CONTEXT: Lumbar spinal canal stenosis (LSCS) is the most common spinal degenerative disorder in elderly people and usually first seen by primary care physicians or orthopedic surgeons who are not spine surgery specialists. Magnetic resonance imaging (MRI) is useful in the diagnosis of LSCS, but the equipment is often not available or difficult to read. LSCS patients with progressive neurologic deficits have difficulty with recovery if surgical treatment is delayed. So, early diagnosis and determination of appropriate surgical indications are crucial in the treatment of LSCS. Convolutional neural networks (CNNs), a type of deep learning, offers significant advantages for image recognition and classification, and work well with radiographs, which can be easily taken at any facility. PURPOSE: Our purpose was to develop an algorithm to diagnose the presence or absence of LSCS requiring surgery from plain radiographs using CNNs. STUDY DESIGN: Retrospective analysis of consecutive, nonrandomized series of patients at a single institution. PATIENT SAMPLE: Data of 150 patients who underwent surgery for LSCS, including degenerative spondylolisthesis, at a single institution from January 2022 to August 2022, were collected. Additionally, 25 patients who underwent surgery at 2 other hospitals were included for extra external validation. OUTCOME MEASURES: In annotation 1, the area under the curve (AUC) computed from the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were calculated. In annotation 2, correlation coefficients were used. METHODS: Four intervertebral levels from L1/2 to L4/5 were extracted as region of interest from lateral plain lumbar spine radiographs totaling 600 images were obtained. Based on the date of surgery, 500 images derived from the first 125 cases were used for internal validation, and 100 images from the subsequent 25 cases used for external validation. Additionally, 100 images from other hospitals were used for extra external validation. In annotation 1, binary classification of operative and nonoperative levels was used, and in annotation 2, the spinal canal area measured on axial MRI was labeled as the output layer. For internal validation, the 500 images were divided into each 5 dataset on per-patient basis and 5-fold cross-validation was performed. Five trained models were registered in the external validation prediction performance. Grad-CAM was used to visualize area with the high features extracted by CNNs. RESULTS: In internal validation, the AUC and accuracy for annotation 1 ranged between 0.85-0.89 and 79-83%, respectively, and the correlation coefficients for annotation 2 ranged between 0.53 and 0.64 (all p<.01). In external validation, the AUC and accuracy for annotation 1 were 0.90 and 82%, respectively, and the correlation coefficient for annotation 2 was 0.69, using 5 trained CNN models. In the extra external validation, the AUC and accuracy for annotation 1 were 0.89 and 84%, respectively, and the correlation coefficient for annotation 2 was 0.56. Grad-CAM showed high feature density in the intervertebral joints and posterior intervertebral discs. CONCLUSIONS: This technology automatically detects LSCS from plain lumbar spine radiographs, making it possible for medical facilities without MRI or nonspecialists to diagnose LSCS, suggesting the possibility of eliminating delays in the diagnosis and treatment of LSCS that require early treatment.

Effect of urgent surgery within 8 hours compared to surgery between 8 and 24 hours on perioperative complications and neurological prognosis in patients older than 70 years with cervical spinal cord injury: a propensity score-matched analysis.

OBJECTIVE: This study aimed to investigate the effect of surgery within 8 hours on perioperative complications and neurological prognosis in older patients with cervical spinal cord injury by using a propensity score-matched analysis. METHODS: The authors included 87 consecutive patients older than 70 years who had cervical spinal cord injury and who had undergone posterior decompression and fusion surgery within 24 hours of injury. The patients were divided into two groups based on the time from injury to surgery: surgery within 8 hours (group 8 hours) and between 8 and 24 hours (group 8-24 hours). Following the preliminary study, the authors established a 1:1 matched model using propensity scores to adjust for baseline characteristics and neurological status on admission. Perioperative complication rates and neurological outcomes at discharge were compared between the two groups. RESULTS: Preliminary analysis of 87 prematched patients (39 in group 8 hours and 48 in group 8-24 hours) revealed that the motor index score (MIS) on admission was lower for lower extremities (12.3 ± 15.5 vs 20.0 ± 18.6, respectively; p = 0.048), and total extremities (26.7 ± 27.1 vs 40.2 ± 30.6, respectively; p = 0.035) in group 8 hours. In terms of perioperative complications, group 8 hours had significantly higher rates of cardiopulmonary dysfunction (46.2% vs 25.0%, respectively; p = 0.039). MIS improvement (the difference in scores between admission and discharge) was greater in group 8 hours for lower extremities (15.8 ± 12.6 vs 9.0 ± 10.5, respectively; p = 0.009) and total extremities (29.4 ± 21.7 vs 18.7 ± 17.7, respectively; p = 0.016). Using a 1:1 propensity score-matched analysis, 29 patient pairs from group 8 hours and group 8-24 hours were selected. There were no significant differences in baseline characteristics, neurological status on admission, and perioperative complications between the two groups, including cardiopulmonary dysfunction. Even after matching, MIS improvement was significantly greater in group 8 hours for upper extremities (13.0 ± 10.9 vs 7.8 ± 8.3, respectively; p = 0.045), lower extremities (14.8 ± 12.7 vs 8.3 ± 11.0, respectively; p = 0.044) and total extremities (27.8 ± 21.0 vs 16.0 ± 17.5, respectively; p = 0.026). CONCLUSIONS: Results of the comparison after matching demonstrated that urgent surgery within 8 hours did not increase the perioperative complication rate and significantly improved the MIS, suggesting that surgery within 8 hours may be efficient, even in older patients.

Development of Notch-Free, Pre-Bent Rod Applicable for Posterior Corrective Surgery of Thoracolumbar/Lumbar Adolescent Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS), the most common pediatric musculoskeletal disorder, causes a three-dimensional spine deformity. Lenke type 5 AIS is defined as a structural thoracolumbar/lumbar curve with nonstructural thoracic curves. Although a rod curvature will affect clinical outcomes, intraoperative contouring of the straight rod depends on the surgeon's knowledge and experience. This study aimed to determine the optimum rod geometries to provide a pre-bent rod system for posterior spinal surgery in patients with Lenke type 5 AIS. These pre-bent rods will be beneficial for achieving proper postoperative outcomes without rod contouring based on surgeon experience. We investigated 20 rod geometries traced in posterior spinal reconstruction in patients with Lenke type 5 AIS. The differences between the center point clouds in each cluster were evaluated using the iterative closest point (ICP) method with modification. Before the evaluation using the ICP method, the point clouds were divided into four clusters based on the rod length using a hierarchical cluster analysis. Because the differences in the values derived from the ICP method were <5 mm for each length-based cluster, four representative rod shapes were generated from the length-based clusters. We identified four optimized rod shapes that will reduce operation time, leading to a decreased patient and surgeon burden.

High whole-body bone mineral density in ossification of the posterior longitudinal ligament.

BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.

Quantitative Assessment of Intervertebral Disc Composition by MRI: Sensitivity to Diurnal Variation.

Whether diurnal variation exists in quantitative MRI indices such as the T1rho relaxation time (T1ρ) of the intervertebral disc (IVD) is yet to be explored. This prospective study aimed to evaluate the diurnal variation in T1ρ, apparent diffusion coefficient (ADC), and electrical conductivity (σ) of lumbar IVD and its relationship with other MRI or clinical indices. Lumbar spine MRI, including T1ρ imaging, diffusion-weighted imaging (DWI), and electric properties tomography (EPT), was conducted on 17 sedentary workers twice (morning and evening) on the same day. The T1ρ, ADC, and σ of IVD were compared between the time points. Their diurnal variation, if any, was tested for correlation with age, body mass index (BMI), IVD level, Pfirrmann grade, scan interval, and diurnal variation in IVD height index. The results showed a significant decrease in T1ρ and ADC and a significant increase in the σ of IVD in the evening. T1ρ variation had a weak correlation with age and scan interval, and ADC variation with scan interval. Diurnal variation exists for the T1ρ, ADC, and σ of lumbar IVD, which should be accounted for in image interpretation. This variation is thought to be due to diurnal variations in intradiscal water, proteoglycan, and sodium ion concentration.

Evaluation of Surgical Indications for Full Endoscopic Discectomy at Lumbosacral Disc Levels Using Three-Dimensional Magnetic Resonance/Computed Tomography Fusion Images Created with Artificial Intelligence.

Background and Objectives: Although full endoscopic lumbar discectomy with the transforaminal approach (FED-TF) is a minimally invasive spinal surgery for lumbar disc herniation, the lumbosacral levels present anatomical challenges when performing FED-TF surgery due to the presence of the iliac bone. Materials and Methods: In this study, we simulated whether FED-TF surgery could be safely performed on a total of 52 consecutive cases with L5-S1 or L5-L6 disc herniation using fused three-dimensional (3D) images of the lumbar nerve root on magnetic resonance imaging (MRI) created with artificial intelligence and of the lumbosacral spine and iliac on computed tomography (CT) images. Results: Thirteen of the fifty-two cases were deemed operable according to simulated FED-TF surgery without foraminoplasty using the 3D MRI/CT fusion images. All 13 cases underwent FED-TF surgery without neurological complications, and their clinical symptoms significantly improved. Conclusions: Three-dimensional simulation may allow for the assessment from multiple angles of the endoscope entry and path, as well as the insertion angle. FED-TF surgery simulation using 3D MRI/CT fusion images could be useful in determining the indications for full endoscopic surgery for lumbosacral disc herniation.

Influence of Lateral Translation of Lowest Instrumented Vertebra on L4 Tilt and Coronal Balance for Thoracolumbar and Lumbar Curves in Adolescent Idiopathic Scoliosis.

This study aimed to evaluate the lowest instrumented vertebra translation (LIV-T) in the surgical treatment of thoracolumbar/lumbar adolescent idiopathic scoliosis and to analyze the radiographic parameters in relation to LIV-T and L4 tilt and global coronal balance. A total of 62 patients underwent posterior spinal fusion (PSF, n = 32) or anterior spinal fusion (ASF, n = 30) and were followed up for a minimum of 2 years. The mean preoperative LIV-T was significantly larger in the ASF group than the PSF (p < 0.01), while the final LIV-T was equivalent. LIV-T at the final follow-up was significantly correlated with L4 tilt and the global coronal balance (r = 0.69, p < 0.01, r = 0.38, p < 0.01, respectively). Receiver-operating characteristic analysis for good outcomes, with L4 tilt <8° and coronal balance <15 mm at the final follow-up, calculated the cutoff value of the final LIV-T as 12 mm. The cutoff value of preoperative LIV-T that would result in the LIV-T of ≤12 mm at the final follow-up was 32 mm in PSF, although no significant cutoff value was calculated in ASF. ASF can centralize the LIV better than PSF with a shorter segment fusion, and could be useful in obtaining a good curve correction and global balance without fixation to L4 in cases with large preoperative LIV-T.

Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model.

Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.

Prediction of Cobb Angle Using Deep Learning Algorithm with Three-Dimensional Depth Sensor Considering the Influence of Garment in Idiopathic Scoliosis.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal deformity. Early detection of deformity and timely intervention, such as brace treatment, can help inhibit progressive changes. A three-dimensional (3D) depth-sensor imaging system with a convolutional neural network was previously developed to predict the Cobb angle. The purpose of the present study was to (1) evaluate the performance of the deep learning algorithm (DLA) in predicting the Cobb angle and (2) assess the predictive ability depending on the presence or absence of clothing in a prospective analysis. We included 100 subjects with suspected AIS. The correlation coefficient between the actual and predicted Cobb angles was 0.87, and the mean absolute error and root mean square error were 4.7° and 6.0°, respectively, for Adam's forward bending without underwear. There were no significant differences in the correlation coefficients between the groups with and without underwear in the forward-bending posture. The performance of the DLA with a 3D depth sensor was validated using an independent external validation dataset. Because the psychological burden of children and adolescents on naked body imaging is an unignorable problem, scoliosis examination with underwear is a valuable alternative in clinics or schools.

Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.

Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.

Posterolateral full-endoscopic debridement and irrigation is effective in treating thoraco-lumbar pyogenic spondylodiscitis, except in cases with large abscess cavities.

PURPOSE: To determine the efficacy and poor prognostic factors of posterolateral full-endoscopic debridement and irrigation (PEDI) surgery for thoraco-lumbar pyogenic spondylodiscitis. METHODS: We included 64 patients (46 men, 18 women; average age: 63.7 years) with thoracic/lumbar pyogenic spondylodiscitis who had undergone PEDI treatment and were followed up for more than 2 years. Clinical outcomes after PEDI surgery were retrospectively investigated to analyze the incidence and risk factors for prolonged and recurrent infection. RESULTS: Of 64 patients, 53 (82.8%) were cured of infection after PEDI surgery, and nine (17.2%) had prolonged or recurrent infection. Multivariate analysis demonstrated that significant risk factors for poor prognosis included a large intervertebral abscess cavity (P = 0.02) and multilevel intervertebral infections (P < 0.05). CONCLUSION: PEDI treatment is an effective, minimally invasive procedure for pyogenic spondylodiscitis. However, a large intervertebral abscess space could cause instability at the infected spinal column, leading to prolonged or recurrent infection after PEDI. In cases with a large abscess cavity with or without vertebral bone destruction, endoscopic drainage alone may have a poor prognosis, and spinal fixation surgery could be considered.

Aggravation of Ossified Ligamentum Flavum Lesion Is Associated With the Degree of Obesity.

STUDY DESIGN: Retrospective cross-sectional study. OBJECTIVES: There is insufficient data on the clinical features of ossification of the ligamentum flavum (OLF) of the thoracic spine and the risk of progression of ossified lesions. The link between obesity and ossification of the posterior longitudinal ligament (OPLL), which frequently coexists with OLF, has been demonstrated. However, the link between obesity and OLF has not been recognized. We aimed to determine the prevalence of obesity in thoracic OLF and whether the severity of OLF is associated with the degree of obesity. METHODS: A total of 204 symptomatic Japanese subjects with thoracic OLF and 136 subjects without spinal ligament ossification as controls were included. OLF subjects were divided into 3 groups: 1) localized OLF (OLF <2-intervertebral regions); 2) multilevel OLF (OLF ≥3-intervertebral regions); and 3) OLF + OPLL. The severity of OLF was quantified using the OLF index using computed tomography imaging of the entire spine. RESULTS: The proportion of severely obese subjects (BMI ≥ 30 kg/m2) was significantly higher both in the multilevel OLF group (25.5%) and the OLF + OPLL group (44.3%) than in the localized OLF group (3.6%) and the control group (1.4%) (P < 0.01). BMI, age, and coexistence of cervical OPLL and lumbar OLF were associated with thoracic OLF index in the multiple regression analysis. CONCLUSIONS: Our findings demonstrated that obesity is a distinct feature of multilevel OLF in the thoracic spine and that the severity of OLF is associated with the degree of obesity.

Strong relationship between dyslipidemia and the ectopic ossification of the spinal ligaments.

Obesity and metabolic disturbances are prevalent in ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF); however, the involvement of dyslipidemia (DL) in OPLL/OLF remains uncertain. We investigated the association between dyslipidemia and OPLL/OLF using a dataset of 458 individuals receiving health screening tests, including computed tomography. Subjects were grouped according to the presence or location of OPLL/OLF: controls (no OPLL/OLF, n = 230), OLF (n = 167), cervical OPLL (n = 28), and thoracic OPLL (n = 33). They were also grouped according to the presence of dyslipidemia (DL[+], n = 215; DL[-], n = 243). The proportion of dyslipidemia in the OLF and OPLL groups was 1.6-2.2 times higher than that in the control group. The proportion of OLF and OPLL in the DL(+) group was significantly higher than that in the DL(-) group (OLF, 43% vs. 29%; cervical OPLL, 14.4% vs. 3.2%; thoracic OPLL, 11.1% vs. 3.7%). Multivariate logistic regression analysis showed an association between all ossification types and dyslipidemia. This study demonstrated an association of dyslipidemia with OPLL/OLF; further investigation on the causal relationship between dyslipidemia and ectopic spinal ligament ossification is warranted to develop a therapeutic intervention for OPLL/OLF.

Long-Term Clinical Course of Patients After Decompression and Posterior Instrumented Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament: An Average Follow-Up of 18 years.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: To evaluate the long-term recurrence rates and functional status of patients with thoracic ossification of the posterior longitudinal ligament (OPLL) after decompression and posterior fusion surgery. METHODS: Thirty-seven consecutive patients who underwent posterior thoracic spine surgery at a single institution were retrospectively reviewed. The long-term neurological and functional outcomes of 25 patients who were followed up for ≥10 years after surgery were assessed. Factors associated with the recurrence of myelopathy were also analyzed. RESULTS: The mean preoperative Japanese Orthopaedic Association score was 3.7, which improved to 6.5 at postoperative year 2 and declined to 6.0 at a mean follow-up of 18 years. No patient experienced a relapse of myelopathy due to OPLL within the instrumented spinal segments. However, 15 (60%) patients experienced late neurological deterioration, 10 of whom had a relapse of myelopathy due to OPLL or ossification of the ligamentum flavum (OLF) in the region outside the primary operative lesion, while 4 developed myelopathy due to traumatic vertebral fracture of the ankylosed spine. Young age, a high body mass index, and lumbar OPLL are likely associated with late neurological deterioration. CONCLUSIONS: Decompression and posterior instrumented fusion surgery is a reliable surgical procedure with stable long-term clinical outcomes for thoracic OPLL. However, as OPLL may progress through the spine, attention should be paid to the recurrence of paralysis due to OPLL or OLF in regions other than the primary operative lesion and vertebral fractures of the ankylosed spine after surgery for thoracic OPLL.

Real-world persistence of twice-weekly teriparatide and factors associated with the discontinuation in patients with osteoporosis.

INTRODUCTION: A 28.2 µg twice-weekly formulation of teriparatide (2/W-TPD) was developed to provide comparably high efficacy for osteoporosis to a 56.5 µg once-weekly formulation while improving the safety and persistence rate. In the current study, we aimed to elucidate the real-world persistence of 2/W-TPD and to identify the factors associated with the discontinuation of 2/W-TPD in patients with severe osteoporosis. MATERIALS AND METHODS: This retrospective study included 90 patients who were treated with 2/W-TPD at three hospitals in Japan. Patient information was collected, including age, sex, distance to the hospital, family structure, comorbidities, previous treatment for osteoporosis, timing of the injection, side effects and duration of 2/W-TPD treatment, barthel index (BI), and bone mineral density (BMD) of the lumbar spine and femoral neck. We examined the factors influencing 2/W-TPD discontinuation using the Cox proportional hazards model. RESULTS: The 12 month completion rate of 2/W-TPD therapy was 47.5%. The Cox hazard analysis identified side effects [Hazard Ratio (HR) = 14.59, P < 0.001], low BMD of the femoral neck (HR = 0.04, P = 0.002), and morning injection (HR = 3.29, P = 0.006) as risk factors influencing the discontinuation of 2/W-TPD. Other variables, including age, did not contribute to the continuation of 2/W-TPD. CONCLUSION: One year continuation rate of 2/W-TPD was higher than the previously reported value of the once-weekly formulation in real-world setting, probably due to the lower incidence of side effects. Introducing injection of 2/W-TPD may further improve the persistence of TPD therapy for osteoporosis.

Distinct progression pattern of ossification of the posterior longitudinal ligament of the thoracic spine versus the cervical spine: a longitudinal whole-spine CT study.

OBJECTIVE: Data regarding risk factors for the progression of ossification of the posterior longitudinal ligament (OPLL) in the thoracic spine are scarce. Therefore, in this study, the authors aimed to elucidate the difference in the radiographic progression pattern of OPLL and its risk factors between cervical and thoracic OPLL using longitudinally acquired whole-spine CT scans. METHODS: Overall, 123 patients with symptomatic OPLL who underwent repeated whole-spine CT examinations, with an average interval of 49 months (at least 3 years) between scans, were retrospectively reviewed. Progression of OPLL was assessed to compare the distribution of OPLL over the entire spine on the initial and final CT scans. Patients were divided into a cervical OPLL (C-OPLL) group and a thoracic OPLL (T-OPLL) group according to the location of the main lesion. The progression pattern of OPLL and its risk factors were compared between the two groups using the Student t-test or Mann-Whitney U-test. RESULTS: In the C-OPLL group, 15 (22.1%) of 68 patients had OPLL progression, of whom 12 patients (80.0%) had progression only in the cervical spine and 3 patients (20.0%) had progression in multiple regions (cervical and thoracic/lumbar). In the T-OPLL group, 16 (29.1%) of 55 patients had OPLL progression, of which 3 patients (18.8%) had progression only in the thoracic spine and 8 patients (50.0%) had progression in multiple regions. Young age was a common risk factor for OPLL progression regardless of the location of OPLL, and this trend was more pronounced in the T-OPLL group than in the C-OPLL group. High BMI, male sex, and multilevel, severe T-OPLL were identified as independent risk factors for progression of T-OPLL (OR 1.19, 95% CI 1.03-1.37; OR 10.5, 95% CI 1.39-81.94; and OR 1.24, 95% CI 1.16-1.45, respectively). CONCLUSIONS: Patients with T-OPLL are predisposed to diffuse progression of OPLL over the entire spine, whereas patients with C-OPLL are likely to have progression in only the cervical spine. Young age and high BMI are significant risk factors for OPLL progression, especially in patients with T-OPLL. Our study highlights the need for continued follow-up in patients with T-OPLL, especially in young patients and those with obesity, for early detection of spinal cord and cauda equina symptoms due to the progression of OPLL throughout the spine.

Biomaterials and Cell-Based Regenerative Therapies for Intervertebral Disc Degeneration with a Focus on Biological and Biomechanical Functional Repair: Targeting Treatments for Disc Herniation.

Intervertebral disc (IVD) degeneration is a common cause of low back pain and most spinal disorders. As IVD degeneration is a major obstacle to the healthy life of so many individuals, it is a major issue that needs to be overcome. Currently, there is no clinical treatment for the regeneration of degenerated IVDs. However, recent advances in regenerative medicine and tissue engineering suggest the potential of cell-based and/or biomaterial-based IVD regeneration therapies. These treatments may be indicated for patients with IVDs in the intermediate degenerative stage, a point where the number of viable cells decreases, and the structural integrity of the disc begins to collapse. However, there are many biological, biomechanical, and clinical challenges that must be overcome before the clinical application of these IVD regeneration therapies can be realized. This review summarizes the basic research and clinical trials literature on cell-based and biomaterial-based IVD regenerative therapies and outlines the important role of these strategies in regenerative treatment for IVD degenerative diseases, especially disc herniation.

Metabolites Produced by a New Lactiplantibacillus plantarum Strain BF1-13 Isolated from Deep Seawater of Izu-Akazawa Protect the Intestinal Epithelial Barrier from the Dysfunction Induced by Hydrogen Peroxide.

This study aimed to investigate the protective effect of the metabolites produced by a new Lactiplantibacillus plantarum strain BF1-13, isolated from deep seawater (DSW), on the intestinal epithelial barrier against the dysfunction induced by hydrogen peroxide (H2O2) and to elucidate the mechanism underlying the effect. Protective effect of the metabolites by strain BF1-13 on the barrier function of the intestinal epithelial model treated with H2O2 was investigated by the transepithelial electrical resistance (TEER). The metabolites enhanced the Claudin-4 (CLDN-4) expression, including at the transcription level, indicated by immunofluorescence staining and quantitative RT-PCR. The metabolites also showed a suppression of aquaporin3 (AQP3) expression. Lactic acid (LA) produced by this strain of homofermentative lactic acid bacteria (LAB) had a similar enhancement on CLDN-4 expression. The metabolites of L. plantarum strain BF1-13 alleviated the dysfunction of intestinal epithelial barrier owing to its enhancement on the tight junctions (TJs) by LA, along with its suppression on AQP3-facilitating H2O2 intracellular invasion into Caco-2 cells. This is the first report on the enhancement of TJs by LA produced by LAB.